A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.

She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
 

A. Topiramate

B. Beta-blocker

C. Lasmiditan

D. Metoclopramide plus sumatriptan

E. Ubrogepant

It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies. This column will focus on some migraine therapy pearls.

DKart/iStockphoto

For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.

When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.¹ Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.

Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.

Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.²

In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.³ There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.

Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.⁴ In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).

In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).⁵
 

Pearl

Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.

2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.

3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.

4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.

5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.

A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.

She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
 

A. Topiramate

B. Beta-blocker

C. Lasmiditan

D. Metoclopramide plus sumatriptan

E. Ubrogepant

It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies. This column will focus on some migraine therapy pearls.

DKart/iStockphoto

For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.

When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.¹ Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.

Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.

Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.²

In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.³ There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.

Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.⁴ In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).

In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).⁵
 

Pearl

Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.

2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.

3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.

4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.

5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.

A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.

She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
 

A. Topiramate

B. Beta-blocker

C. Lasmiditan

D. Metoclopramide plus sumatriptan

E. Ubrogepant

It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies. This column will focus on some migraine therapy pearls.

DKart/iStockphoto

For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.

When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.¹ Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.

Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.

Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.²

In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.³ There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.

Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.⁴ In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).

In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).⁵
 

Pearl

Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.

2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.

3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.

4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.

5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.

Ixekizumab appears to be a safe and effective treatment for patients with pityriasis rubra pilaris refractory to other systemic therapies, Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.

The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.

PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.

Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.

The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.

Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.

The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.

The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.

To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.

No serious or unexpected adverse events occurred in the 24-week study.

“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.

Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.

“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.

Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.

“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.

She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.

Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.

bjancin@mdedge.com

Ixekizumab appears to be a safe and effective treatment for patients with pityriasis rubra pilaris refractory to other systemic therapies, Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.

The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.

PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.

Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.

The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.

Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.

The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.

The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.

To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.

No serious or unexpected adverse events occurred in the 24-week study.

“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.

Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.

“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.

Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.

“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.

She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.

Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.

bjancin@mdedge.com

Ixekizumab appears to be a safe and effective treatment for patients with pityriasis rubra pilaris refractory to other systemic therapies, Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.

The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.

PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.

Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.

The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.

Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.

The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.

The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.

To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.

No serious or unexpected adverse events occurred in the 24-week study.

“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.

Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.

“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.

Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.

“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.

She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.

Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.

bjancin@mdedge.com

Reducing the dosing frequency of intravesical bacillus Calmette-Guérin (BCG) was associated with a higher rate of disease recurrence among patients with high-grade non-muscle invasive bladder cancer (NMIBC) in the phase 3 NIMBUS trial.

The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.

More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.

At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.

“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.

“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.

Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.

Trial details

NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.

The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.

Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.

Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.

“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.

Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.

“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
 

Post hoc analysis

Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.

The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).

However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).

Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.

Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.

“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.

“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”

“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.

The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.

SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/

Reducing the dosing frequency of intravesical bacillus Calmette-Guérin (BCG) was associated with a higher rate of disease recurrence among patients with high-grade non-muscle invasive bladder cancer (NMIBC) in the phase 3 NIMBUS trial.

The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.

More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.

At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.

“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.

“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.

Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.

Trial details

NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.

The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.

Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.

Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.

“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.

Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.

“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
 

Post hoc analysis

Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.

The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).

However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).

Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.

Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.

“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.

“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”

“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.

The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.

SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/

Reducing the dosing frequency of intravesical bacillus Calmette-Guérin (BCG) was associated with a higher rate of disease recurrence among patients with high-grade non-muscle invasive bladder cancer (NMIBC) in the phase 3 NIMBUS trial.

The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.

More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.

At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.

“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.

“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.

Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.

Trial details

NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.

The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.

Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.

Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.

“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.

Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.

“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
 

Post hoc analysis

Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.

The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).

However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).

Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.

Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.

“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.

“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”

“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.

The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.

SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.

Howard Shooter/Thinkstock

Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.

The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.

Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.

The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.

“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.

The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.

Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.

However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.

Every physician encounters difficult or challenging patients during their career, but learning how to anticipate and handle these interactions is not something taught in medical school or residency, according to Donald W. Black, MD, MS.

Courtesy Dr. Donald Black

Difficult or challenging encounters with patients are not only unavoidable, they should be expected, Dr. Black said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Every doctor I know has had challenging interactions,” he said. About 15% of encounters were deemed “difficult” in a prospective study of patients by Jeffrey L. Jackson, MD, MPH, and Kurt Kroenke, MD. A depressive or anxiety disorder was present in 29% of patients, with 11% experiencing two or more disorders. Major depression was present in 8.4%, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2% of patients. Dr. Jackson and Dr. Kroenke found that difficult patients demonstrated disrespect and anger, made threats, and locked themselves in rooms (Arch Intern Med. 1999 May 24;159[10]:1069-75). “Rest assured, you are not the only psychiatrist to face this type of issue,” Dr. Black said at the meeting, presented by Global Academy for Medical Education.

Common scenarios can include patients who want certain tests performed after researching symptoms online, threats of legal or social media action after feeling like they are not being listened to, a demand for a second opinion after not agreeing with a physician’s diagnosis, mistrust of doctors after presenting with symptoms and not being diagnosed, patients who focus on negative outcomes, and those who do not comply with treatment. These patients can often appear angry, defensive, frightened or resistant, or manipulative; may provide vague or exaggerated symptoms; or may inappropriately rely on hospital or clinic staff for emotional and physical support.

To complicate matters, the patients’ condition also might contribute to difficult interactions, such as in patients who have conditions like chronic pain or fibromyalgia.

“These often contribute because patients never feel that their problems are being appropriately addressed,” said Dr. Black, professor of psychiatry at the University of Iowa in Iowa City. Patients with psychiatric disorders can also present unique challenges that may result in difficult encounters. Patients with anxiety might not be able to be reassured by their doctor, for example, or patients with eating disorders might refuse treatment recommendations, he said.

Difficult encounters can lead to physicians feeling angry, upset, stressed, disrespected, abused, or fearful. But “it’s not just about the patient,” Dr. Black said. Physicians can become angry or defensive because of burnout, stress, or frustration, which can lead to them snapping at patients. Physicians are also overworked, sleep-deprived, and busier than they’d like to be, he added. Personal problems can contribute, and a physician’s belief system can cause a bad interaction with a patient. If physicians “label” one of their patients, that might end up becoming a “self-fulfilling prophecy” for that patient, Dr. Black said. Poor communication, such as not conveying bad news appropriately or with empathy, seeing a patient but never making eye contact, and using medical jargon that could be confusing to the patient, also can contribute to a challenging encounter, he added.

Situational issues also might create a bad experience for the patient. For example, a patient might find it hard to make an appointment, or the clinic might be busy or have a lack of privacy or encounter administrative issues. For patients who do not speak English as their native language, not having access to an interpreter can lead to frustration on the part of both the physician and the patient. “Bad interactions are not good for patient care,” Dr. Black said.

The key to resolving these issues is to focus on the goal, Dr. Black said. “We all want the same thing. We want to help the patient get better; we want to keep patients healthy; we want to keep them happy; we want to be fulfilled; [and] we want to manage our time and make a living – and meet our professional expectations.”

Begin by recognizing the difficult situation and assessing how the patient, the environment, or you might be contributing to the problem. “You have to step back and say what’s going on with this, and what are the factors that are combining to create this situation,” Dr. Black said. It is important to be calm and professional and not argue or talk over the patient. The goal is to work with the patient to find a solution.

One technique is to verbalize the problem without blaming the patient, the physician, or the environment (“We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?”).

There also might be alternative explanations for a patient’s behavior. For example, anger could be misdirected at a physician because of anxiety surrounding an unrelated event. In this case, it is important to listen to the patient and empathize, which will help the patient feel supported and build a rapport that can aid in resolving the problem encounter, Dr. Black said. Finding common ground when patients and physicians have different ideas on treatment or diagnosis is another way to help resolve a difficult encounter.

However, setting boundaries also is important, he noted. If, after remediation or if patients demonstrate signs of threatening or abusive behavior, initiate sexual advances, refuse to follow a treatment plan, fail to pay their bills, or are potentially putting themselves in harm’s way through noncompliance, a physician might consider terminating the relationship. Terminating the patient relationship should be done after attempting to work with the patient through a case manager and team members, and clearly advising a patient about behavior that could lead to termination of the patient-provider relationship. “If the problem is irremediable, notify the patient in writing and allow time for the patient to find another doctor,” Dr. Black said.

Global Academy and this news organization are owned by the same parent company. Dr. Black reported that he is a consultant for Otsuka and receives royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. In addition, he receives funding from Nellie Ball Trust, the National Institute on Drug Abuse, the National Institute on Aging, and the National Center for Responsible Gaming.

Every physician encounters difficult or challenging patients during their career, but learning how to anticipate and handle these interactions is not something taught in medical school or residency, according to Donald W. Black, MD, MS.

Courtesy Dr. Donald Black

Difficult or challenging encounters with patients are not only unavoidable, they should be expected, Dr. Black said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Every doctor I know has had challenging interactions,” he said. About 15% of encounters were deemed “difficult” in a prospective study of patients by Jeffrey L. Jackson, MD, MPH, and Kurt Kroenke, MD. A depressive or anxiety disorder was present in 29% of patients, with 11% experiencing two or more disorders. Major depression was present in 8.4%, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2% of patients. Dr. Jackson and Dr. Kroenke found that difficult patients demonstrated disrespect and anger, made threats, and locked themselves in rooms (Arch Intern Med. 1999 May 24;159[10]:1069-75). “Rest assured, you are not the only psychiatrist to face this type of issue,” Dr. Black said at the meeting, presented by Global Academy for Medical Education.

Common scenarios can include patients who want certain tests performed after researching symptoms online, threats of legal or social media action after feeling like they are not being listened to, a demand for a second opinion after not agreeing with a physician’s diagnosis, mistrust of doctors after presenting with symptoms and not being diagnosed, patients who focus on negative outcomes, and those who do not comply with treatment. These patients can often appear angry, defensive, frightened or resistant, or manipulative; may provide vague or exaggerated symptoms; or may inappropriately rely on hospital or clinic staff for emotional and physical support.

To complicate matters, the patients’ condition also might contribute to difficult interactions, such as in patients who have conditions like chronic pain or fibromyalgia.

“These often contribute because patients never feel that their problems are being appropriately addressed,” said Dr. Black, professor of psychiatry at the University of Iowa in Iowa City. Patients with psychiatric disorders can also present unique challenges that may result in difficult encounters. Patients with anxiety might not be able to be reassured by their doctor, for example, or patients with eating disorders might refuse treatment recommendations, he said.

Difficult encounters can lead to physicians feeling angry, upset, stressed, disrespected, abused, or fearful. But “it’s not just about the patient,” Dr. Black said. Physicians can become angry or defensive because of burnout, stress, or frustration, which can lead to them snapping at patients. Physicians are also overworked, sleep-deprived, and busier than they’d like to be, he added. Personal problems can contribute, and a physician’s belief system can cause a bad interaction with a patient. If physicians “label” one of their patients, that might end up becoming a “self-fulfilling prophecy” for that patient, Dr. Black said. Poor communication, such as not conveying bad news appropriately or with empathy, seeing a patient but never making eye contact, and using medical jargon that could be confusing to the patient, also can contribute to a challenging encounter, he added.

Situational issues also might create a bad experience for the patient. For example, a patient might find it hard to make an appointment, or the clinic might be busy or have a lack of privacy or encounter administrative issues. For patients who do not speak English as their native language, not having access to an interpreter can lead to frustration on the part of both the physician and the patient. “Bad interactions are not good for patient care,” Dr. Black said.

The key to resolving these issues is to focus on the goal, Dr. Black said. “We all want the same thing. We want to help the patient get better; we want to keep patients healthy; we want to keep them happy; we want to be fulfilled; [and] we want to manage our time and make a living – and meet our professional expectations.”

Begin by recognizing the difficult situation and assessing how the patient, the environment, or you might be contributing to the problem. “You have to step back and say what’s going on with this, and what are the factors that are combining to create this situation,” Dr. Black said. It is important to be calm and professional and not argue or talk over the patient. The goal is to work with the patient to find a solution.

One technique is to verbalize the problem without blaming the patient, the physician, or the environment (“We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?”).

There also might be alternative explanations for a patient’s behavior. For example, anger could be misdirected at a physician because of anxiety surrounding an unrelated event. In this case, it is important to listen to the patient and empathize, which will help the patient feel supported and build a rapport that can aid in resolving the problem encounter, Dr. Black said. Finding common ground when patients and physicians have different ideas on treatment or diagnosis is another way to help resolve a difficult encounter.

However, setting boundaries also is important, he noted. If, after remediation or if patients demonstrate signs of threatening or abusive behavior, initiate sexual advances, refuse to follow a treatment plan, fail to pay their bills, or are potentially putting themselves in harm’s way through noncompliance, a physician might consider terminating the relationship. Terminating the patient relationship should be done after attempting to work with the patient through a case manager and team members, and clearly advising a patient about behavior that could lead to termination of the patient-provider relationship. “If the problem is irremediable, notify the patient in writing and allow time for the patient to find another doctor,” Dr. Black said.

Global Academy and this news organization are owned by the same parent company. Dr. Black reported that he is a consultant for Otsuka and receives royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. In addition, he receives funding from Nellie Ball Trust, the National Institute on Drug Abuse, the National Institute on Aging, and the National Center for Responsible Gaming.

Every physician encounters difficult or challenging patients during their career, but learning how to anticipate and handle these interactions is not something taught in medical school or residency, according to Donald W. Black, MD, MS.

Courtesy Dr. Donald Black

Difficult or challenging encounters with patients are not only unavoidable, they should be expected, Dr. Black said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“Every doctor I know has had challenging interactions,” he said. About 15% of encounters were deemed “difficult” in a prospective study of patients by Jeffrey L. Jackson, MD, MPH, and Kurt Kroenke, MD. A depressive or anxiety disorder was present in 29% of patients, with 11% experiencing two or more disorders. Major depression was present in 8.4%, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2% of patients. Dr. Jackson and Dr. Kroenke found that difficult patients demonstrated disrespect and anger, made threats, and locked themselves in rooms (Arch Intern Med. 1999 May 24;159[10]:1069-75). “Rest assured, you are not the only psychiatrist to face this type of issue,” Dr. Black said at the meeting, presented by Global Academy for Medical Education.

Common scenarios can include patients who want certain tests performed after researching symptoms online, threats of legal or social media action after feeling like they are not being listened to, a demand for a second opinion after not agreeing with a physician’s diagnosis, mistrust of doctors after presenting with symptoms and not being diagnosed, patients who focus on negative outcomes, and those who do not comply with treatment. These patients can often appear angry, defensive, frightened or resistant, or manipulative; may provide vague or exaggerated symptoms; or may inappropriately rely on hospital or clinic staff for emotional and physical support.

To complicate matters, the patients’ condition also might contribute to difficult interactions, such as in patients who have conditions like chronic pain or fibromyalgia.

“These often contribute because patients never feel that their problems are being appropriately addressed,” said Dr. Black, professor of psychiatry at the University of Iowa in Iowa City. Patients with psychiatric disorders can also present unique challenges that may result in difficult encounters. Patients with anxiety might not be able to be reassured by their doctor, for example, or patients with eating disorders might refuse treatment recommendations, he said.

Difficult encounters can lead to physicians feeling angry, upset, stressed, disrespected, abused, or fearful. But “it’s not just about the patient,” Dr. Black said. Physicians can become angry or defensive because of burnout, stress, or frustration, which can lead to them snapping at patients. Physicians are also overworked, sleep-deprived, and busier than they’d like to be, he added. Personal problems can contribute, and a physician’s belief system can cause a bad interaction with a patient. If physicians “label” one of their patients, that might end up becoming a “self-fulfilling prophecy” for that patient, Dr. Black said. Poor communication, such as not conveying bad news appropriately or with empathy, seeing a patient but never making eye contact, and using medical jargon that could be confusing to the patient, also can contribute to a challenging encounter, he added.

Situational issues also might create a bad experience for the patient. For example, a patient might find it hard to make an appointment, or the clinic might be busy or have a lack of privacy or encounter administrative issues. For patients who do not speak English as their native language, not having access to an interpreter can lead to frustration on the part of both the physician and the patient. “Bad interactions are not good for patient care,” Dr. Black said.

The key to resolving these issues is to focus on the goal, Dr. Black said. “We all want the same thing. We want to help the patient get better; we want to keep patients healthy; we want to keep them happy; we want to be fulfilled; [and] we want to manage our time and make a living – and meet our professional expectations.”

Begin by recognizing the difficult situation and assessing how the patient, the environment, or you might be contributing to the problem. “You have to step back and say what’s going on with this, and what are the factors that are combining to create this situation,” Dr. Black said. It is important to be calm and professional and not argue or talk over the patient. The goal is to work with the patient to find a solution.

One technique is to verbalize the problem without blaming the patient, the physician, or the environment (“We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?”).

There also might be alternative explanations for a patient’s behavior. For example, anger could be misdirected at a physician because of anxiety surrounding an unrelated event. In this case, it is important to listen to the patient and empathize, which will help the patient feel supported and build a rapport that can aid in resolving the problem encounter, Dr. Black said. Finding common ground when patients and physicians have different ideas on treatment or diagnosis is another way to help resolve a difficult encounter.

However, setting boundaries also is important, he noted. If, after remediation or if patients demonstrate signs of threatening or abusive behavior, initiate sexual advances, refuse to follow a treatment plan, fail to pay their bills, or are potentially putting themselves in harm’s way through noncompliance, a physician might consider terminating the relationship. Terminating the patient relationship should be done after attempting to work with the patient through a case manager and team members, and clearly advising a patient about behavior that could lead to termination of the patient-provider relationship. “If the problem is irremediable, notify the patient in writing and allow time for the patient to find another doctor,” Dr. Black said.

Global Academy and this news organization are owned by the same parent company. Dr. Black reported that he is a consultant for Otsuka and receives royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. In addition, he receives funding from Nellie Ball Trust, the National Institute on Drug Abuse, the National Institute on Aging, and the National Center for Responsible Gaming.

Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression.

A new review by investigators led by John Read, PhD, University of East London, conclude there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective.

However, the review’s conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions.

“We’ve concluded there is no adequate research on which to base an answer to the question, ‘Does ECT work?,’ ” Read told Medscape Medical News. “We’re not actually saying ECT doesn’t work. We’re saying there’s no way to know whether it works or not on the basis of the current research, which, after 80 years of the treatment being used, is pretty amazing.”

On the other hand, Read said there is substantial evidence to suggest ECT causes significant adverse events. “Depending who you ask, the psychiatrists or the patients, somewhere between 12% and 55% of patients get permanent or persistent memory loss,” he said.

“So there is a very serious cost to its use, and if there’s a serious cost, you ... have to know that there’s a very strong efficacy benefit, and we just don’t know that. That’s why we’re calling for suspension until there is adequate research,” Read added.

The study was published in a recent issue of Ethical Human Psychology and Psychiatry.
 

Widespread use

ECT remains a popular treatment modality for resistant depression. Global data show that it is used to treat almost a million patients every year. Although ECT continues to be the subject of comparative research, the investigators say that most of these studies do not adhere to the same standards that govern clinical trials of other psychiatric medications and medical interventions.

The investigators also note that to date, only 11 placebo-controlled studies of the efficacy of ECT have been conducted. They write that the last study to compare ECT with sham or simulated ECT (SECT) – in which a general anesthetic was administered but the electricity was not – was performed in 1985. Nevertheless, this relatively small body of evidence has been the basis of many meta-analyses.

In the current review, the authors evaluated the impartiality and robustness of these previous meta-analyses and the quality of the studies that were included.

“The primary goal is not to assess whether or not ECT is effective,” they write. “The intent, instead, is to determine whether the available evidence is robust enough to answer that question.”

For Read, the decision to analyze the current state of ECT research was both personal and professional.

“As a young nursing attendant in a Bronx hospital, I had the job of sitting with people as they came around from ECT. It was my job to try to explain why they didn’t know who they were, where they were, why their head was throbbing, and why people would do something like that to them,” he said.

“On the research side, this is my sixth review, and in each one we’ve reached the same conclusion,” Read added.

Other research stands in direct opposition to the current review’s findings. Many studies have concluded that ECT is safe and effective for patients with depression.
 

Ongoing debate

A 2018 registry analysis showed no additional risk for cognitive impairment in patients who underwent ECT up to 40 years after therapy. A 2018 study also showed that ECT was efficacious and cost-effective for patients with treatment-resistant depression.

However, the ECT debate continues. As reported early last year, there seems to be little common ground between clinicians who believe in the utility of ECT for depression and those who vehemently do not.

For the current review, Read and colleagues performed a Medline search for meta-analyses of the efficacy of ECT for depression. Meta-analyses were only included if they comprised placebo-controlled trials that compared ECT with SECT.

Once the meta-analyses were identified, investigators assessed their component studies. This assessment was conducted by two independent reviewers who used a 24-point quality scale developed by the authors. This scale, the authors note, combines the “risk of bias” domains of the Cochrane Handbook Risk of Bias Tool with criteria related to quality of study design and reporting, as well as several criteria specific to ECT research.

The two reviewers were blinded to each other’s ratings. Interrater differences were resolved collectively.

The literature search yielded 83 potential articles; after exclusion criteria were applied, 14 remained. Three of these articles were literature reviews, one discussed different types of statistical analyses used in ECT research, one was a meta-analysis in Hungarian, one was a meta-analysis that compared ECT with SECT in a selected population of elderly people, and three focused on transcranial magnetic stimulation.

This left five meta-analyses for the review. These included from 1 to 7 of the 11 studies in question:

• Janicak et al, 1985 
• Kho, van Vreewijk, Simpson, & Zwinderman, 2003 
• Mutz et al, 2019 
• Pagnin, de Queiroz, Pini, & Cassano, 2004 
• UK ECT Review Group, 2003

The review revealed shortcomings with both the meta-analyses and the studies they included. The investigators found that the mean quality scores of the 11 studies (10.27 ± 2.45 and 11.91 ± 2.91) were not statistically different between the two raters (P = .17), whose scores were significantly correlated (P = .001).

Among the 264 total ratings, the investigators found 55 inconsistencies, which were all resolved by discussion. The mean final quality score for the 11 studies included in the review was 12.27 ± 3.20/24; eight scored 13 or less.

The results of these studies do little to support the benefits of ECT relative to SECT, the reviewers note. Indeed, only four concluded that ECT is significantly superior to SECT. Five found no significant difference, and the remaining two had mixed results.

What’s more, only two of what the investigators describe as “higher quality” studies reported follow-up data. Of these, one produced an effect size of 0.065 favoring ECT, the other showed a small benefit in favor of SECT (effect size, 0.299).

The investigators describe the five meta-analyses included in the review as “flawed,” stating that the meta-analyses “pay little or no attention to the multiple limitations of the studies they include.”

These limitations include the number of patients included in the studies (which average 37 patients); lack of a description of randomization and blinding processes; lack of patient ratings; selective reporting of findings; and the absence of assessment of patient quality of life. Furthermore, the authors note that none of the 11 studies “convincingly” demonstrate double-blinding.

Given these shortcomings, the investigators say the meta-analyses of ECT fail to prove the following:

• The short- and long-term efficacy benefits of ECT over SECT;
• Whether ECT is effective among patients who have failed other treatments for depression;
• Whether ECT prevents ;
• Whether ECT improves patients’ quality of life;
• Whether ECT is more effective in women than men;
• Whether ECT is effective in children or adolescents.

“Shoddy” research

The authors conclude that the review’s findings demonstrate the weakness of evidence that currently supports the use of ECT for depression.

“I would never have guessed how shoddy some of this research was,” said review coauthor Irving Kirsch, PhD, a lecturer on medicine at Beth Israel Deaconess Medical Center, Boston. Many of these shortcomings, Kirsch said, involve blinding and placebo effects.

“It’s not clear how you could ever run a truly blinded trial of ECT, given how pronounced the immediate side effects are,” he told Medscape Medical News. “And one of the things that’s underappreciated is the pronounced responses to placebo treatment with depression and severe depression. These can last for a very long time.”

Kirsch noted that more invasive placebo treatments, such as SECT, tend to have more pronounced effects.

“Not all placebos are created equal. We know, for example, that placebo injections are more effective than placebo pills and that placebo surgery can be extremely powerful,” he said.

The authors call for an immediate suspension of ECT until new studies address these research shortcomings.

“The doctors who perform ECT aren’t evil or stupid, they’re just ignorant of the research. What they see is very temporary benefit in some of the patients. The research suggests that about a third – half at most – get a very temporary lift in mood, which seems to be the sort of euphoria you get from mild brain injury,” Read explained.

“I have seen people who haven’t spoken or eaten for several weeks start speaking and eating, but we know that 4 weeks later, they’re going to be just as depressed as they were, or worse. And now they’re going to have brain damage as well,” said Read.

He added that physicians often don’t see long-term patient outcomes, just the immediate effect of ECT.
 

A “lifesaver”

No recent randomized controlled trials regarding ECT have been conducted because “no IRB [institutional review board] on planet earth will allow such a trial because of the overwhelming evidence of efficacy and the risk of anesthesia with no ECT,” noted Mark S. George, MD, the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina, Charleston.

It is a “logical fallacy” to conclude that ECT does not work because the trials were flawed, said George, who was not involved with the current review

“This is not supported by anything they have looked at,” he told Medscape Medical News. “It’s not really a scientific study when you make conclusions that aren’t based on your data, or not what you set out to do. That’s what I find egregious here.”

The way he sees it, the utility of ECT is unquestionable. “It is our most effective acute treatment for depression, and it’s our most effective treatment for suicide,” he said.

“The authors of this review don’t see the patients that I see every day, who are catatonic, who can’t eat, who are suicidal. For those people, ECT is a lifesaver,” George added.
 

FDA’s position

Sameer Jauhar, MBChB, PhD, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, London, was equally unimpressed with the quality of the review.

“I try to approach everything with an open mind,” he said. “But as a doctor, if I’m reading about evidence, I expect a well-conducted meta-analysis and/or very clear systematic review with an adequate level of peer review.”

The current review, said Jauhar, doesn’t meet these criteria. He said the article reads more like a narrative review, one in which the authors dictated their own arbitrary criteria of study quality.

Most important, he said, is the fact that ECT has been the focus of a great deal of research. “The best quality synthesis of the evidence I’ve come across is the UK ECT Review Group’s 2003 meta-analysis, published in The Lancet, which asked this very question. None of the studies has changed since then.”

Jauhar also noted that in 2018, the Food and Drug Administration reclassified ECT from class III (higher risk) to class II (moderate risk). Use of ECT was also limited to treatment of “catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition.”

The FDA also noted that “[t]he safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices.”

As part of the FDA’s 2018 reclassification, ECT manufacturers were required to file a premarket approval application for all uses that were not reclassified. The full text of the order is available in the Federal Register.

“So the FDA has been through it, The Lancet has been through it, and the findings were clear,” said Jauhar. “It’s very easy to poke holes in studies that were conducted 30 or more years ago. But the fact is, the field has moved on.”

Jauhar acknowledged there are patients who have had bad experiences with ECT, and he accepts that such events occasionally occur. Nevertheless, he said, “as a piece of scientific work, I don’t know how anyone can give any credibility to this review at all.”

Jauhar also noted that the journal in which the review was published has a 2019 CiteScore of 0.3 and ranks in the 15th percentile of the Scopus Clinical Psychology category. He further noted that Kirsch is a member of the journal’s editorial board.

“I would say that the level of peer review here was negligible at best,” Jauhar said. “In addition, the ‘findings’ are driven more by ideology than evidence.”

Asked to respond to Jauhar’s comments, Kirsch noted that although he is on the journal’s advisory board, he has not been actively involved. Kirsch added that he serves on about a dozen academic advisory boards and serves as a reviewer for many top scientific and medical journals, including The Journal of the American Medical Association and the New England Journal of Medicine.

“Our article was peer reviewed,” Kirsch said, “and we revised it following the first round of reviews.” The review process did not differ from those he has gone through with more than 250 published peer-reviewed articles on which he was an author or coauthor, he noted.
 

A growing movement

Despite such expert opposition, the movement to suspend ECT continues. Recently, Sarah Price Hancock, MS, CRC, CPMC, who is herself a recipient of more than 100 ECT treatments, authored an international petition to standardize, regulate, and audit the modality. Hancock hopes to present the document, which currently has more than 6600 signatures, to the American Psychiatric Association and similar international societies.

A version of the petition was presented to the UK’s National Health Service on July 2, the 59th anniversary of the death by suicide of Ernest Hemingway, who had received some 20 ECT treatments himself.

“Hopefully by his 60th anniversary, America and the world will be taking his death and the thousands living with adverse reactions more seriously by auditing, regulating, and tracking patients with a history of ECT to provide much needed comprehensive brain injury rehabilitation as necessary,” Hancock told Medscape Medical News.

Among the signatories of the petition is Sue Cunliffe, MbChB, who underwent ECT for depression in 2004, with devastating effects. “I was left really badly brain damaged, and so I’ve never been allowed to work again,” she told Medscape Medical News.

Cunliffe said the immediate effects of the treatment were profound. She said her hands shook, her balance and coordination were impaired, and her memories evaporated. However, she found a neuropsychologist who she says was able to help her recover control of her life. “Now at least I’m able to plan my life so that I can live with the brain damage.”

Kirsch acknowledged that sorting through the ECT literature can be daunting. “If you’re a physician, you try to keep up with the literature, but the problem is, the literature is so old and done in ways which would not pass muster right now. The data are really poor, and I guess it’s just that people aren’t aware of it.”

George agreed that the therapy is not without its shortcomings.

“Does ECT have cognitive side effects? Unfortunately, it does. But so do lots of lifesaving therapies in medicine, like cancer chemotherapy,” he said.

“Nobody really gets well with a single ECT session. It’s usually eight to 12 over 3 or 4 weeks. So it’s not particularly durable. That’s why we often combine ECT with other forms of brain stimulation,” George added.

He noted that the recent advent of alternative forms of ECT – including right unilateral ultrabrief pulse ECT and focal electrically administered seizure therapy – are beginning to address some of these shortcomings.

“The holy grail of brain stimulation is to be able to do things less invasively, and we’re moving slowly in that direction,” he said. “But right now, we don’t have anything that is as acutely as effective as ECT. It is our lifesaver at the moment.”

The review authors as well as George, Jauhar, Cunliffe, and Hancock report no relevant financial relationships.

This article first appeared on Medscape.com.

Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression.

A new review by investigators led by John Read, PhD, University of East London, conclude there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective.

However, the review’s conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions.

“We’ve concluded there is no adequate research on which to base an answer to the question, ‘Does ECT work?,’ ” Read told Medscape Medical News. “We’re not actually saying ECT doesn’t work. We’re saying there’s no way to know whether it works or not on the basis of the current research, which, after 80 years of the treatment being used, is pretty amazing.”

On the other hand, Read said there is substantial evidence to suggest ECT causes significant adverse events. “Depending who you ask, the psychiatrists or the patients, somewhere between 12% and 55% of patients get permanent or persistent memory loss,” he said.

“So there is a very serious cost to its use, and if there’s a serious cost, you ... have to know that there’s a very strong efficacy benefit, and we just don’t know that. That’s why we’re calling for suspension until there is adequate research,” Read added.

The study was published in a recent issue of Ethical Human Psychology and Psychiatry.
 

Widespread use

ECT remains a popular treatment modality for resistant depression. Global data show that it is used to treat almost a million patients every year. Although ECT continues to be the subject of comparative research, the investigators say that most of these studies do not adhere to the same standards that govern clinical trials of other psychiatric medications and medical interventions.

The investigators also note that to date, only 11 placebo-controlled studies of the efficacy of ECT have been conducted. They write that the last study to compare ECT with sham or simulated ECT (SECT) – in which a general anesthetic was administered but the electricity was not – was performed in 1985. Nevertheless, this relatively small body of evidence has been the basis of many meta-analyses.

In the current review, the authors evaluated the impartiality and robustness of these previous meta-analyses and the quality of the studies that were included.

“The primary goal is not to assess whether or not ECT is effective,” they write. “The intent, instead, is to determine whether the available evidence is robust enough to answer that question.”

For Read, the decision to analyze the current state of ECT research was both personal and professional.

“As a young nursing attendant in a Bronx hospital, I had the job of sitting with people as they came around from ECT. It was my job to try to explain why they didn’t know who they were, where they were, why their head was throbbing, and why people would do something like that to them,” he said.

“On the research side, this is my sixth review, and in each one we’ve reached the same conclusion,” Read added.

Other research stands in direct opposition to the current review’s findings. Many studies have concluded that ECT is safe and effective for patients with depression.
 

Ongoing debate

A 2018 registry analysis showed no additional risk for cognitive impairment in patients who underwent ECT up to 40 years after therapy. A 2018 study also showed that ECT was efficacious and cost-effective for patients with treatment-resistant depression.

However, the ECT debate continues. As reported early last year, there seems to be little common ground between clinicians who believe in the utility of ECT for depression and those who vehemently do not.

For the current review, Read and colleagues performed a Medline search for meta-analyses of the efficacy of ECT for depression. Meta-analyses were only included if they comprised placebo-controlled trials that compared ECT with SECT.

Once the meta-analyses were identified, investigators assessed their component studies. This assessment was conducted by two independent reviewers who used a 24-point quality scale developed by the authors. This scale, the authors note, combines the “risk of bias” domains of the Cochrane Handbook Risk of Bias Tool with criteria related to quality of study design and reporting, as well as several criteria specific to ECT research.

The two reviewers were blinded to each other’s ratings. Interrater differences were resolved collectively.

The literature search yielded 83 potential articles; after exclusion criteria were applied, 14 remained. Three of these articles were literature reviews, one discussed different types of statistical analyses used in ECT research, one was a meta-analysis in Hungarian, one was a meta-analysis that compared ECT with SECT in a selected population of elderly people, and three focused on transcranial magnetic stimulation.

This left five meta-analyses for the review. These included from 1 to 7 of the 11 studies in question:

• Janicak et al, 1985 
• Kho, van Vreewijk, Simpson, & Zwinderman, 2003 
• Mutz et al, 2019 
• Pagnin, de Queiroz, Pini, & Cassano, 2004 
• UK ECT Review Group, 2003

The review revealed shortcomings with both the meta-analyses and the studies they included. The investigators found that the mean quality scores of the 11 studies (10.27 ± 2.45 and 11.91 ± 2.91) were not statistically different between the two raters (P = .17), whose scores were significantly correlated (P = .001).

Among the 264 total ratings, the investigators found 55 inconsistencies, which were all resolved by discussion. The mean final quality score for the 11 studies included in the review was 12.27 ± 3.20/24; eight scored 13 or less.

The results of these studies do little to support the benefits of ECT relative to SECT, the reviewers note. Indeed, only four concluded that ECT is significantly superior to SECT. Five found no significant difference, and the remaining two had mixed results.

What’s more, only two of what the investigators describe as “higher quality” studies reported follow-up data. Of these, one produced an effect size of 0.065 favoring ECT, the other showed a small benefit in favor of SECT (effect size, 0.299).

The investigators describe the five meta-analyses included in the review as “flawed,” stating that the meta-analyses “pay little or no attention to the multiple limitations of the studies they include.”

These limitations include the number of patients included in the studies (which average 37 patients); lack of a description of randomization and blinding processes; lack of patient ratings; selective reporting of findings; and the absence of assessment of patient quality of life. Furthermore, the authors note that none of the 11 studies “convincingly” demonstrate double-blinding.

Given these shortcomings, the investigators say the meta-analyses of ECT fail to prove the following:

• The short- and long-term efficacy benefits of ECT over SECT;
• Whether ECT is effective among patients who have failed other treatments for depression;
• Whether ECT prevents ;
• Whether ECT improves patients’ quality of life;
• Whether ECT is more effective in women than men;
• Whether ECT is effective in children or adolescents.

“Shoddy” research

The authors conclude that the review’s findings demonstrate the weakness of evidence that currently supports the use of ECT for depression.

“I would never have guessed how shoddy some of this research was,” said review coauthor Irving Kirsch, PhD, a lecturer on medicine at Beth Israel Deaconess Medical Center, Boston. Many of these shortcomings, Kirsch said, involve blinding and placebo effects.

“It’s not clear how you could ever run a truly blinded trial of ECT, given how pronounced the immediate side effects are,” he told Medscape Medical News. “And one of the things that’s underappreciated is the pronounced responses to placebo treatment with depression and severe depression. These can last for a very long time.”

Kirsch noted that more invasive placebo treatments, such as SECT, tend to have more pronounced effects.

“Not all placebos are created equal. We know, for example, that placebo injections are more effective than placebo pills and that placebo surgery can be extremely powerful,” he said.

The authors call for an immediate suspension of ECT until new studies address these research shortcomings.

“The doctors who perform ECT aren’t evil or stupid, they’re just ignorant of the research. What they see is very temporary benefit in some of the patients. The research suggests that about a third – half at most – get a very temporary lift in mood, which seems to be the sort of euphoria you get from mild brain injury,” Read explained.

“I have seen people who haven’t spoken or eaten for several weeks start speaking and eating, but we know that 4 weeks later, they’re going to be just as depressed as they were, or worse. And now they’re going to have brain damage as well,” said Read.

He added that physicians often don’t see long-term patient outcomes, just the immediate effect of ECT.
 

A “lifesaver”

No recent randomized controlled trials regarding ECT have been conducted because “no IRB [institutional review board] on planet earth will allow such a trial because of the overwhelming evidence of efficacy and the risk of anesthesia with no ECT,” noted Mark S. George, MD, the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina, Charleston.

It is a “logical fallacy” to conclude that ECT does not work because the trials were flawed, said George, who was not involved with the current review

“This is not supported by anything they have looked at,” he told Medscape Medical News. “It’s not really a scientific study when you make conclusions that aren’t based on your data, or not what you set out to do. That’s what I find egregious here.”

The way he sees it, the utility of ECT is unquestionable. “It is our most effective acute treatment for depression, and it’s our most effective treatment for suicide,” he said.

“The authors of this review don’t see the patients that I see every day, who are catatonic, who can’t eat, who are suicidal. For those people, ECT is a lifesaver,” George added.
 

FDA’s position

Sameer Jauhar, MBChB, PhD, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, London, was equally unimpressed with the quality of the review.

“I try to approach everything with an open mind,” he said. “But as a doctor, if I’m reading about evidence, I expect a well-conducted meta-analysis and/or very clear systematic review with an adequate level of peer review.”

The current review, said Jauhar, doesn’t meet these criteria. He said the article reads more like a narrative review, one in which the authors dictated their own arbitrary criteria of study quality.

Most important, he said, is the fact that ECT has been the focus of a great deal of research. “The best quality synthesis of the evidence I’ve come across is the UK ECT Review Group’s 2003 meta-analysis, published in The Lancet, which asked this very question. None of the studies has changed since then.”

Jauhar also noted that in 2018, the Food and Drug Administration reclassified ECT from class III (higher risk) to class II (moderate risk). Use of ECT was also limited to treatment of “catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition.”

The FDA also noted that “[t]he safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices.”

As part of the FDA’s 2018 reclassification, ECT manufacturers were required to file a premarket approval application for all uses that were not reclassified. The full text of the order is available in the Federal Register.

“So the FDA has been through it, The Lancet has been through it, and the findings were clear,” said Jauhar. “It’s very easy to poke holes in studies that were conducted 30 or more years ago. But the fact is, the field has moved on.”

Jauhar acknowledged there are patients who have had bad experiences with ECT, and he accepts that such events occasionally occur. Nevertheless, he said, “as a piece of scientific work, I don’t know how anyone can give any credibility to this review at all.”

Jauhar also noted that the journal in which the review was published has a 2019 CiteScore of 0.3 and ranks in the 15th percentile of the Scopus Clinical Psychology category. He further noted that Kirsch is a member of the journal’s editorial board.

“I would say that the level of peer review here was negligible at best,” Jauhar said. “In addition, the ‘findings’ are driven more by ideology than evidence.”

Asked to respond to Jauhar’s comments, Kirsch noted that although he is on the journal’s advisory board, he has not been actively involved. Kirsch added that he serves on about a dozen academic advisory boards and serves as a reviewer for many top scientific and medical journals, including The Journal of the American Medical Association and the New England Journal of Medicine.

“Our article was peer reviewed,” Kirsch said, “and we revised it following the first round of reviews.” The review process did not differ from those he has gone through with more than 250 published peer-reviewed articles on which he was an author or coauthor, he noted.
 

A growing movement

Despite such expert opposition, the movement to suspend ECT continues. Recently, Sarah Price Hancock, MS, CRC, CPMC, who is herself a recipient of more than 100 ECT treatments, authored an international petition to standardize, regulate, and audit the modality. Hancock hopes to present the document, which currently has more than 6600 signatures, to the American Psychiatric Association and similar international societies.

A version of the petition was presented to the UK’s National Health Service on July 2, the 59th anniversary of the death by suicide of Ernest Hemingway, who had received some 20 ECT treatments himself.

“Hopefully by his 60th anniversary, America and the world will be taking his death and the thousands living with adverse reactions more seriously by auditing, regulating, and tracking patients with a history of ECT to provide much needed comprehensive brain injury rehabilitation as necessary,” Hancock told Medscape Medical News.

Among the signatories of the petition is Sue Cunliffe, MbChB, who underwent ECT for depression in 2004, with devastating effects. “I was left really badly brain damaged, and so I’ve never been allowed to work again,” she told Medscape Medical News.

Cunliffe said the immediate effects of the treatment were profound. She said her hands shook, her balance and coordination were impaired, and her memories evaporated. However, she found a neuropsychologist who she says was able to help her recover control of her life. “Now at least I’m able to plan my life so that I can live with the brain damage.”

Kirsch acknowledged that sorting through the ECT literature can be daunting. “If you’re a physician, you try to keep up with the literature, but the problem is, the literature is so old and done in ways which would not pass muster right now. The data are really poor, and I guess it’s just that people aren’t aware of it.”

George agreed that the therapy is not without its shortcomings.

“Does ECT have cognitive side effects? Unfortunately, it does. But so do lots of lifesaving therapies in medicine, like cancer chemotherapy,” he said.

“Nobody really gets well with a single ECT session. It’s usually eight to 12 over 3 or 4 weeks. So it’s not particularly durable. That’s why we often combine ECT with other forms of brain stimulation,” George added.

He noted that the recent advent of alternative forms of ECT – including right unilateral ultrabrief pulse ECT and focal electrically administered seizure therapy – are beginning to address some of these shortcomings.

“The holy grail of brain stimulation is to be able to do things less invasively, and we’re moving slowly in that direction,” he said. “But right now, we don’t have anything that is as acutely as effective as ECT. It is our lifesaver at the moment.”

The review authors as well as George, Jauhar, Cunliffe, and Hancock report no relevant financial relationships.

This article first appeared on Medscape.com.

Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression.

A new review by investigators led by John Read, PhD, University of East London, conclude there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective.

However, the review’s conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions.

“We’ve concluded there is no adequate research on which to base an answer to the question, ‘Does ECT work?,’ ” Read told Medscape Medical News. “We’re not actually saying ECT doesn’t work. We’re saying there’s no way to know whether it works or not on the basis of the current research, which, after 80 years of the treatment being used, is pretty amazing.”

On the other hand, Read said there is substantial evidence to suggest ECT causes significant adverse events. “Depending who you ask, the psychiatrists or the patients, somewhere between 12% and 55% of patients get permanent or persistent memory loss,” he said.

“So there is a very serious cost to its use, and if there’s a serious cost, you ... have to know that there’s a very strong efficacy benefit, and we just don’t know that. That’s why we’re calling for suspension until there is adequate research,” Read added.

The study was published in a recent issue of Ethical Human Psychology and Psychiatry.
 

Widespread use

ECT remains a popular treatment modality for resistant depression. Global data show that it is used to treat almost a million patients every year. Although ECT continues to be the subject of comparative research, the investigators say that most of these studies do not adhere to the same standards that govern clinical trials of other psychiatric medications and medical interventions.

The investigators also note that to date, only 11 placebo-controlled studies of the efficacy of ECT have been conducted. They write that the last study to compare ECT with sham or simulated ECT (SECT) – in which a general anesthetic was administered but the electricity was not – was performed in 1985. Nevertheless, this relatively small body of evidence has been the basis of many meta-analyses.

In the current review, the authors evaluated the impartiality and robustness of these previous meta-analyses and the quality of the studies that were included.

“The primary goal is not to assess whether or not ECT is effective,” they write. “The intent, instead, is to determine whether the available evidence is robust enough to answer that question.”

For Read, the decision to analyze the current state of ECT research was both personal and professional.

“As a young nursing attendant in a Bronx hospital, I had the job of sitting with people as they came around from ECT. It was my job to try to explain why they didn’t know who they were, where they were, why their head was throbbing, and why people would do something like that to them,” he said.

“On the research side, this is my sixth review, and in each one we’ve reached the same conclusion,” Read added.

Other research stands in direct opposition to the current review’s findings. Many studies have concluded that ECT is safe and effective for patients with depression.
 

Ongoing debate

A 2018 registry analysis showed no additional risk for cognitive impairment in patients who underwent ECT up to 40 years after therapy. A 2018 study also showed that ECT was efficacious and cost-effective for patients with treatment-resistant depression.

However, the ECT debate continues. As reported early last year, there seems to be little common ground between clinicians who believe in the utility of ECT for depression and those who vehemently do not.

For the current review, Read and colleagues performed a Medline search for meta-analyses of the efficacy of ECT for depression. Meta-analyses were only included if they comprised placebo-controlled trials that compared ECT with SECT.

Once the meta-analyses were identified, investigators assessed their component studies. This assessment was conducted by two independent reviewers who used a 24-point quality scale developed by the authors. This scale, the authors note, combines the “risk of bias” domains of the Cochrane Handbook Risk of Bias Tool with criteria related to quality of study design and reporting, as well as several criteria specific to ECT research.

The two reviewers were blinded to each other’s ratings. Interrater differences were resolved collectively.

The literature search yielded 83 potential articles; after exclusion criteria were applied, 14 remained. Three of these articles were literature reviews, one discussed different types of statistical analyses used in ECT research, one was a meta-analysis in Hungarian, one was a meta-analysis that compared ECT with SECT in a selected population of elderly people, and three focused on transcranial magnetic stimulation.

This left five meta-analyses for the review. These included from 1 to 7 of the 11 studies in question:

• Janicak et al, 1985 
• Kho, van Vreewijk, Simpson, & Zwinderman, 2003 
• Mutz et al, 2019 
• Pagnin, de Queiroz, Pini, & Cassano, 2004 
• UK ECT Review Group, 2003

The review revealed shortcomings with both the meta-analyses and the studies they included. The investigators found that the mean quality scores of the 11 studies (10.27 ± 2.45 and 11.91 ± 2.91) were not statistically different between the two raters (P = .17), whose scores were significantly correlated (P = .001).

Among the 264 total ratings, the investigators found 55 inconsistencies, which were all resolved by discussion. The mean final quality score for the 11 studies included in the review was 12.27 ± 3.20/24; eight scored 13 or less.

The results of these studies do little to support the benefits of ECT relative to SECT, the reviewers note. Indeed, only four concluded that ECT is significantly superior to SECT. Five found no significant difference, and the remaining two had mixed results.

What’s more, only two of what the investigators describe as “higher quality” studies reported follow-up data. Of these, one produced an effect size of 0.065 favoring ECT, the other showed a small benefit in favor of SECT (effect size, 0.299).

The investigators describe the five meta-analyses included in the review as “flawed,” stating that the meta-analyses “pay little or no attention to the multiple limitations of the studies they include.”

These limitations include the number of patients included in the studies (which average 37 patients); lack of a description of randomization and blinding processes; lack of patient ratings; selective reporting of findings; and the absence of assessment of patient quality of life. Furthermore, the authors note that none of the 11 studies “convincingly” demonstrate double-blinding.

Given these shortcomings, the investigators say the meta-analyses of ECT fail to prove the following:

• The short- and long-term efficacy benefits of ECT over SECT;
• Whether ECT is effective among patients who have failed other treatments for depression;
• Whether ECT prevents ;
• Whether ECT improves patients’ quality of life;
• Whether ECT is more effective in women than men;
• Whether ECT is effective in children or adolescents.

“Shoddy” research

The authors conclude that the review’s findings demonstrate the weakness of evidence that currently supports the use of ECT for depression.

“I would never have guessed how shoddy some of this research was,” said review coauthor Irving Kirsch, PhD, a lecturer on medicine at Beth Israel Deaconess Medical Center, Boston. Many of these shortcomings, Kirsch said, involve blinding and placebo effects.

“It’s not clear how you could ever run a truly blinded trial of ECT, given how pronounced the immediate side effects are,” he told Medscape Medical News. “And one of the things that’s underappreciated is the pronounced responses to placebo treatment with depression and severe depression. These can last for a very long time.”

Kirsch noted that more invasive placebo treatments, such as SECT, tend to have more pronounced effects.

“Not all placebos are created equal. We know, for example, that placebo injections are more effective than placebo pills and that placebo surgery can be extremely powerful,” he said.

The authors call for an immediate suspension of ECT until new studies address these research shortcomings.

“The doctors who perform ECT aren’t evil or stupid, they’re just ignorant of the research. What they see is very temporary benefit in some of the patients. The research suggests that about a third – half at most – get a very temporary lift in mood, which seems to be the sort of euphoria you get from mild brain injury,” Read explained.

“I have seen people who haven’t spoken or eaten for several weeks start speaking and eating, but we know that 4 weeks later, they’re going to be just as depressed as they were, or worse. And now they’re going to have brain damage as well,” said Read.

He added that physicians often don’t see long-term patient outcomes, just the immediate effect of ECT.
 

A “lifesaver”

No recent randomized controlled trials regarding ECT have been conducted because “no IRB [institutional review board] on planet earth will allow such a trial because of the overwhelming evidence of efficacy and the risk of anesthesia with no ECT,” noted Mark S. George, MD, the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina, Charleston.

It is a “logical fallacy” to conclude that ECT does not work because the trials were flawed, said George, who was not involved with the current review

“This is not supported by anything they have looked at,” he told Medscape Medical News. “It’s not really a scientific study when you make conclusions that aren’t based on your data, or not what you set out to do. That’s what I find egregious here.”

The way he sees it, the utility of ECT is unquestionable. “It is our most effective acute treatment for depression, and it’s our most effective treatment for suicide,” he said.

“The authors of this review don’t see the patients that I see every day, who are catatonic, who can’t eat, who are suicidal. For those people, ECT is a lifesaver,” George added.
 

FDA’s position

Sameer Jauhar, MBChB, PhD, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, London, was equally unimpressed with the quality of the review.

“I try to approach everything with an open mind,” he said. “But as a doctor, if I’m reading about evidence, I expect a well-conducted meta-analysis and/or very clear systematic review with an adequate level of peer review.”

The current review, said Jauhar, doesn’t meet these criteria. He said the article reads more like a narrative review, one in which the authors dictated their own arbitrary criteria of study quality.

Most important, he said, is the fact that ECT has been the focus of a great deal of research. “The best quality synthesis of the evidence I’ve come across is the UK ECT Review Group’s 2003 meta-analysis, published in The Lancet, which asked this very question. None of the studies has changed since then.”

Jauhar also noted that in 2018, the Food and Drug Administration reclassified ECT from class III (higher risk) to class II (moderate risk). Use of ECT was also limited to treatment of “catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition.”

The FDA also noted that “[t]he safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices.”

As part of the FDA’s 2018 reclassification, ECT manufacturers were required to file a premarket approval application for all uses that were not reclassified. The full text of the order is available in the Federal Register.

“So the FDA has been through it, The Lancet has been through it, and the findings were clear,” said Jauhar. “It’s very easy to poke holes in studies that were conducted 30 or more years ago. But the fact is, the field has moved on.”

Jauhar acknowledged there are patients who have had bad experiences with ECT, and he accepts that such events occasionally occur. Nevertheless, he said, “as a piece of scientific work, I don’t know how anyone can give any credibility to this review at all.”

Jauhar also noted that the journal in which the review was published has a 2019 CiteScore of 0.3 and ranks in the 15th percentile of the Scopus Clinical Psychology category. He further noted that Kirsch is a member of the journal’s editorial board.

“I would say that the level of peer review here was negligible at best,” Jauhar said. “In addition, the ‘findings’ are driven more by ideology than evidence.”

Asked to respond to Jauhar’s comments, Kirsch noted that although he is on the journal’s advisory board, he has not been actively involved. Kirsch added that he serves on about a dozen academic advisory boards and serves as a reviewer for many top scientific and medical journals, including The Journal of the American Medical Association and the New England Journal of Medicine.

“Our article was peer reviewed,” Kirsch said, “and we revised it following the first round of reviews.” The review process did not differ from those he has gone through with more than 250 published peer-reviewed articles on which he was an author or coauthor, he noted.
 

A growing movement

Despite such expert opposition, the movement to suspend ECT continues. Recently, Sarah Price Hancock, MS, CRC, CPMC, who is herself a recipient of more than 100 ECT treatments, authored an international petition to standardize, regulate, and audit the modality. Hancock hopes to present the document, which currently has more than 6600 signatures, to the American Psychiatric Association and similar international societies.

A version of the petition was presented to the UK’s National Health Service on July 2, the 59th anniversary of the death by suicide of Ernest Hemingway, who had received some 20 ECT treatments himself.

“Hopefully by his 60th anniversary, America and the world will be taking his death and the thousands living with adverse reactions more seriously by auditing, regulating, and tracking patients with a history of ECT to provide much needed comprehensive brain injury rehabilitation as necessary,” Hancock told Medscape Medical News.

Among the signatories of the petition is Sue Cunliffe, MbChB, who underwent ECT for depression in 2004, with devastating effects. “I was left really badly brain damaged, and so I’ve never been allowed to work again,” she told Medscape Medical News.

Cunliffe said the immediate effects of the treatment were profound. She said her hands shook, her balance and coordination were impaired, and her memories evaporated. However, she found a neuropsychologist who she says was able to help her recover control of her life. “Now at least I’m able to plan my life so that I can live with the brain damage.”

Kirsch acknowledged that sorting through the ECT literature can be daunting. “If you’re a physician, you try to keep up with the literature, but the problem is, the literature is so old and done in ways which would not pass muster right now. The data are really poor, and I guess it’s just that people aren’t aware of it.”

George agreed that the therapy is not without its shortcomings.

“Does ECT have cognitive side effects? Unfortunately, it does. But so do lots of lifesaving therapies in medicine, like cancer chemotherapy,” he said.

“Nobody really gets well with a single ECT session. It’s usually eight to 12 over 3 or 4 weeks. So it’s not particularly durable. That’s why we often combine ECT with other forms of brain stimulation,” George added.

He noted that the recent advent of alternative forms of ECT – including right unilateral ultrabrief pulse ECT and focal electrically administered seizure therapy – are beginning to address some of these shortcomings.

“The holy grail of brain stimulation is to be able to do things less invasively, and we’re moving slowly in that direction,” he said. “But right now, we don’t have anything that is as acutely as effective as ECT. It is our lifesaver at the moment.”

The review authors as well as George, Jauhar, Cunliffe, and Hancock report no relevant financial relationships.

This article first appeared on Medscape.com.

Most psychiatrists live at or below their means, and more than half have a net worth of less than $1 million, according to the Medscape Psychiatrist Debt and Net Worth Report 2020.

An important caveat, however, is that the data for this year’s report were collected as part of the Medscape Physician Compensation Report 2020, prior to Feb. 11, 2020 – and before COVID-19 was declared a pandemic.

Although it will be some time before medical practices become accustomed to a new version of normal, the data provide an overall picture of the debt load and net worth of psychiatrists.
 

Among the lowest earners

According to the Medscape Psychiatrist Compensation Report 2020, psychiatrists are among the lowest earners of all physicians, earning $268,000 on average this year. However, that’s up somewhat from last year’s earnings of $260,000.

Among psychiatrists, 57% report a net worth (total assets minus total liabilities) of less than $1 million; 38% have a net worth between $1 million and $5 million, and 5% top $5 million in net worth.

Among specialists, orthopedists are most likely (at 19%) to top the $5 million level, followed by plastic surgeons and gastroenterologists (both at 16%), according to the overall Medscape Physician Debt and Net Worth Report 2020. The report is based on more than 17,000 physicians and spans 30 specialties.

By gender, more female than male psychiatrists have a net worth of less than $1 million (61% vs. 53%). The percentages are closer between female and male psychiatrists who have a net worth between $1 million and $5 million, at 36% and 41%, respectively. In addition, more male than female psychiatrists have a net worth above $5 million (6% vs. 3%).

As expected, the older the physician, the more money they have as earnings increase and early-career debt decreases. This is the case for psychiatrists, whose net worth over $1 million increased with age.

However, psychiatrists are among the most likely of all physicians to have a net worth of less than $500,000 (at 37%), which is on par with public health and preventive medicine physicians (also at 37%) and just below family medicine physicians (at 46%), pediatricians (44%), neurologists (41%), and internal medicine physicians (40%).

For nearly two-thirds of psychiatrists (63%), mortgage payments on their primary residence are the major expense; 39% of psychiatrists have a mortgage of $300,000 or less, and 12% have a mortgage topping $500,000; 31% have no mortgage at all. Six in 10 psychiatrists live in a house that is 3,000 sq ft or smaller.

Mortgage aside, other top ongoing expenses for psychiatrists are car payments (38%), school loan payments (28%), credit card debt (26%), and medical expenses for self or loved one (20%). At 28%, psychiatrists are toward the top of the list of all physicians when it comes to those still paying off loans for education.
 

Spending vs. saving

The average American has four credit cards, according to the credit reporting agency Experian. More than half of psychiatrists said they have four or fewer credit cards (35% have three or four credit cards, 20% have one or two cards, and 1% have none). A quarter of psychiatrists (25%) have five or six credit cards, and 19% have seven or more at their disposal.

Only a small percentage of psychiatrists (7%) say they live above their means; 53% live at their means, and 39% live below their means.

Most psychiatrists (62%) contribute $1,000 or more to a tax-deferred retirement or college savings account each month; 13% do not do this on a regular basis. Nearly two-thirds (65%) of psychiatrists contribute to a taxable savings account, a tool many use when tax-deferred contributions have reached their limit.

Nearly half of psychiatrists (47%) rely on a mental budget for personal expenses; 16% rely on a written budget or use software or an app for budgeting; and 37% don’t have a budget for personal expenses.

Three-quarters of psychiatrists did not experience a financial loss in 2019. Of those who did have a loss, the main causes were bad investments (6%) and practice-related problems (6%). Other factors were job loss (self or spouse/partner), real estate loss (4%), legal fees (3%), and divorce (3%).

Among psychiatrists who have joint finances with a spouse or partner, 51% pool their income to pay household expenses. For 14%, the person who earns more pays more of the bills and/or expenses. Only a small percentage divide bills and expenses equally, regardless of how much each makes (5%).

About 43% of psychiatrists currently work with a financial planner or have done so in the past, 40% never did, and 17% met with a financial planner but did not pursue working with that person.

A version of this article originally appeared on Medscape.com.

Most psychiatrists live at or below their means, and more than half have a net worth of less than $1 million, according to the Medscape Psychiatrist Debt and Net Worth Report 2020.

An important caveat, however, is that the data for this year’s report were collected as part of the Medscape Physician Compensation Report 2020, prior to Feb. 11, 2020 – and before COVID-19 was declared a pandemic.

Although it will be some time before medical practices become accustomed to a new version of normal, the data provide an overall picture of the debt load and net worth of psychiatrists.
 

Among the lowest earners

According to the Medscape Psychiatrist Compensation Report 2020, psychiatrists are among the lowest earners of all physicians, earning $268,000 on average this year. However, that’s up somewhat from last year’s earnings of $260,000.

Among psychiatrists, 57% report a net worth (total assets minus total liabilities) of less than $1 million; 38% have a net worth between $1 million and $5 million, and 5% top $5 million in net worth.

Among specialists, orthopedists are most likely (at 19%) to top the $5 million level, followed by plastic surgeons and gastroenterologists (both at 16%), according to the overall Medscape Physician Debt and Net Worth Report 2020. The report is based on more than 17,000 physicians and spans 30 specialties.

By gender, more female than male psychiatrists have a net worth of less than $1 million (61% vs. 53%). The percentages are closer between female and male psychiatrists who have a net worth between $1 million and $5 million, at 36% and 41%, respectively. In addition, more male than female psychiatrists have a net worth above $5 million (6% vs. 3%).

As expected, the older the physician, the more money they have as earnings increase and early-career debt decreases. This is the case for psychiatrists, whose net worth over $1 million increased with age.

However, psychiatrists are among the most likely of all physicians to have a net worth of less than $500,000 (at 37%), which is on par with public health and preventive medicine physicians (also at 37%) and just below family medicine physicians (at 46%), pediatricians (44%), neurologists (41%), and internal medicine physicians (40%).

For nearly two-thirds of psychiatrists (63%), mortgage payments on their primary residence are the major expense; 39% of psychiatrists have a mortgage of $300,000 or less, and 12% have a mortgage topping $500,000; 31% have no mortgage at all. Six in 10 psychiatrists live in a house that is 3,000 sq ft or smaller.

Mortgage aside, other top ongoing expenses for psychiatrists are car payments (38%), school loan payments (28%), credit card debt (26%), and medical expenses for self or loved one (20%). At 28%, psychiatrists are toward the top of the list of all physicians when it comes to those still paying off loans for education.
 

Spending vs. saving

The average American has four credit cards, according to the credit reporting agency Experian. More than half of psychiatrists said they have four or fewer credit cards (35% have three or four credit cards, 20% have one or two cards, and 1% have none). A quarter of psychiatrists (25%) have five or six credit cards, and 19% have seven or more at their disposal.

Only a small percentage of psychiatrists (7%) say they live above their means; 53% live at their means, and 39% live below their means.

Most psychiatrists (62%) contribute $1,000 or more to a tax-deferred retirement or college savings account each month; 13% do not do this on a regular basis. Nearly two-thirds (65%) of psychiatrists contribute to a taxable savings account, a tool many use when tax-deferred contributions have reached their limit.

Nearly half of psychiatrists (47%) rely on a mental budget for personal expenses; 16% rely on a written budget or use software or an app for budgeting; and 37% don’t have a budget for personal expenses.

Three-quarters of psychiatrists did not experience a financial loss in 2019. Of those who did have a loss, the main causes were bad investments (6%) and practice-related problems (6%). Other factors were job loss (self or spouse/partner), real estate loss (4%), legal fees (3%), and divorce (3%).

Among psychiatrists who have joint finances with a spouse or partner, 51% pool their income to pay household expenses. For 14%, the person who earns more pays more of the bills and/or expenses. Only a small percentage divide bills and expenses equally, regardless of how much each makes (5%).

About 43% of psychiatrists currently work with a financial planner or have done so in the past, 40% never did, and 17% met with a financial planner but did not pursue working with that person.

A version of this article originally appeared on Medscape.com.

Most psychiatrists live at or below their means, and more than half have a net worth of less than $1 million, according to the Medscape Psychiatrist Debt and Net Worth Report 2020.

An important caveat, however, is that the data for this year’s report were collected as part of the Medscape Physician Compensation Report 2020, prior to Feb. 11, 2020 – and before COVID-19 was declared a pandemic.

Although it will be some time before medical practices become accustomed to a new version of normal, the data provide an overall picture of the debt load and net worth of psychiatrists.
 

Among the lowest earners

According to the Medscape Psychiatrist Compensation Report 2020, psychiatrists are among the lowest earners of all physicians, earning $268,000 on average this year. However, that’s up somewhat from last year’s earnings of $260,000.

Among psychiatrists, 57% report a net worth (total assets minus total liabilities) of less than $1 million; 38% have a net worth between $1 million and $5 million, and 5% top $5 million in net worth.

Among specialists, orthopedists are most likely (at 19%) to top the $5 million level, followed by plastic surgeons and gastroenterologists (both at 16%), according to the overall Medscape Physician Debt and Net Worth Report 2020. The report is based on more than 17,000 physicians and spans 30 specialties.

By gender, more female than male psychiatrists have a net worth of less than $1 million (61% vs. 53%). The percentages are closer between female and male psychiatrists who have a net worth between $1 million and $5 million, at 36% and 41%, respectively. In addition, more male than female psychiatrists have a net worth above $5 million (6% vs. 3%).

As expected, the older the physician, the more money they have as earnings increase and early-career debt decreases. This is the case for psychiatrists, whose net worth over $1 million increased with age.

However, psychiatrists are among the most likely of all physicians to have a net worth of less than $500,000 (at 37%), which is on par with public health and preventive medicine physicians (also at 37%) and just below family medicine physicians (at 46%), pediatricians (44%), neurologists (41%), and internal medicine physicians (40%).

For nearly two-thirds of psychiatrists (63%), mortgage payments on their primary residence are the major expense; 39% of psychiatrists have a mortgage of $300,000 or less, and 12% have a mortgage topping $500,000; 31% have no mortgage at all. Six in 10 psychiatrists live in a house that is 3,000 sq ft or smaller.

Mortgage aside, other top ongoing expenses for psychiatrists are car payments (38%), school loan payments (28%), credit card debt (26%), and medical expenses for self or loved one (20%). At 28%, psychiatrists are toward the top of the list of all physicians when it comes to those still paying off loans for education.
 

Spending vs. saving

The average American has four credit cards, according to the credit reporting agency Experian. More than half of psychiatrists said they have four or fewer credit cards (35% have three or four credit cards, 20% have one or two cards, and 1% have none). A quarter of psychiatrists (25%) have five or six credit cards, and 19% have seven or more at their disposal.

Only a small percentage of psychiatrists (7%) say they live above their means; 53% live at their means, and 39% live below their means.

Most psychiatrists (62%) contribute $1,000 or more to a tax-deferred retirement or college savings account each month; 13% do not do this on a regular basis. Nearly two-thirds (65%) of psychiatrists contribute to a taxable savings account, a tool many use when tax-deferred contributions have reached their limit.

Nearly half of psychiatrists (47%) rely on a mental budget for personal expenses; 16% rely on a written budget or use software or an app for budgeting; and 37% don’t have a budget for personal expenses.

Three-quarters of psychiatrists did not experience a financial loss in 2019. Of those who did have a loss, the main causes were bad investments (6%) and practice-related problems (6%). Other factors were job loss (self or spouse/partner), real estate loss (4%), legal fees (3%), and divorce (3%).

Among psychiatrists who have joint finances with a spouse or partner, 51% pool their income to pay household expenses. For 14%, the person who earns more pays more of the bills and/or expenses. Only a small percentage divide bills and expenses equally, regardless of how much each makes (5%).

About 43% of psychiatrists currently work with a financial planner or have done so in the past, 40% never did, and 17% met with a financial planner but did not pursue working with that person.

A version of this article originally appeared on Medscape.com.

An elderly, retired, married African American man sought psychiatric treatment for depression and suicidal thoughts. He had a detailed, lethal suicide plan, but he had not taken any steps to carry it out.

He met DSM-5 criteria for a major depressive episode, and he described a lifelong history of recurrent depressions as well as hypomanic episodes. He was diagnosed with bipolar II disorder, and he began weekly therapy, as well as medication. Despite several static and dynamic suicide risk factors, the psychiatrist also noted that he was help seeking and future oriented. He seemed transparent during his initial appointments. He did not have access to lethal means and welcomed the psychiatrist to communicate openly with his spouse.

The patient had never attempted suicide, there was no family history of suicide, and there was no psychosis or substance use disorder present. He was able to commit to reaching out to the psychiatrist, his spouse, or emergency personnel in the case of worsening suicidal thoughts or imminent suicidal action. He remained in the outpatient setting. His suicidal ideation faded and depression receded as psychotherapy and pharmacotherapy continued.

Discussion

Depression and suicidal ideation are ubiquitous in the practice of psychiatry. Psychiatrists draw from an array of assessment and management tools when this common clinical challenge arises. Among these tools is the no-suicide contract (NSC). The NSC goes by many names, including the no-harm contract and suicide prevention contract.¹ It is a promise, verbal or written, from the patient to not attempt suicide and to tell a loved one or psychiatric provider instead.² The verbal exchange between the patient and therapist described in the case fits the widely accepted clinical definition of an NSC. The contents and implementation of NSCs vary greatly; no standard approach is taught in psychiatric training.³ The American Psychiatric Association has warned against over-reliance on them, emphasizing that they have not been proven effective. It advises that NSCs should not be used independently of other tools or outside well-established patient-provider relationships.⁴ A 2007 review of the literature on NSCs concluded that there were no data to support their effectiveness and some data that they might even cause harm.⁵

The origin of the NSC

The NSC is fairly young and its foundation arguably weak. Its evolution has been traced back to a study published in 1973 by Robert C. Drye, MD, and associates on the effectiveness of a questionnaire for the assessment of suicide risk.⁶ The questionnaire centered on the patient’s reaction to the statement, “No matter what happens, I will not kill myself, accidently or on purpose, at any time.” The authors placed special emphasis on the words “I will,” which they felt to be a stronger indicator of commitment to safety than “I promise.” The authors thought the latter statement sounded like a child’s empty reply to a demanding parent. The authors reported a 100% success rate with “approximately 600 patients” across geographic regions and clinical settings.⁷ The study group is not further described, and that the authors contend that the intervention had “complete effectiveness in evaluating suicide risk” should give pause to anyone aiming to practice evidence-based psychiatry.

The theoretical basis of the NSC has been presumed by others to be based, in part, on the principles of transactional analysis. Specifically, the suicidal patient is seen as occupying the child ego state, and the NSC is seen as a means of moving the patient into the less problematic adult ego state. It has been argued, however, that an NSC can achieve exactly the opposite. The contract can pit the patient against the clinician, entrenching the patient deeper into the child ego and, therefore, suicidal state.⁸

Michael Craig Miller, MD, and associates proposed other psychological reasons why NSCs may be counterproductive. They write, “Psychological pitfalls abound, and any of them may contribute to a contract being thoughtless, unrealistic, irrelevant, cynical, punitive, or coercive.”⁹ They postulated that the NSC grew out of and assumes the same shared decision-making inherent in any therapeutic contract – and they argue that this assumption is flawed given the legal power clinicians have over suicidal patients. While acknowledging this problematic power differential, the authors go on to urge clinicians to aim for shared decision-making and a shared burden of risk when discussing treatment with suicidal patients.

Possible NSC common factors

Psychiatry, like the rest of medicine, is increasingly practiced in an evidence-based manner. The NSC should not be excluded from this movement. To this end, a recently published, randomized study of 97 active duty Army personnel seeking emergency behavioral health evaluation compared the effectiveness of NSCs and with an alternative intervention, the crisis response plan (CRP). The CRP was chosen because it had been suggested by the Joint Commision as an alternative to the NSC, although it also has little evidence supporting its use.¹⁰

The NSC and CRP interventions of the Army study were very similar. Both included suicide risk assessment, supportive listening, provision of crisis resources, and referral to treatment. In addition, the NSC intervention included asking whether the patients could keep themselves safe at home. The CRP intervention included collaboration with the patient to identify warning signs of crisis, self-management skills, and support persons. A seemingly small but interesting difference between the two interventions was which member of the dyad, patient or clinician, created a written record of the discussion. In the NSC group, the assessor did the writing, while in the CRP group, the patient controlled the pen.

The results of the study were intriguing. Suicidal ideation declined faster in the CRP arm. Participants in the CRP arm were 76% less likely to attempt suicide over 6 months, although this effect decreased and lost statistical significance when controlling for baseline severity of suicidal ideation. Despite those promising data, the only completed suicide was in the CRP arm.

The authors compared the makeup of the CRP intervention with key components of dialectical behavior therapy (DBT). They pointed to a 2015 study by Marsha Linehan, PhD, and associates that sought to identify the active ingredients of DBT. The Linehan study indicated that attending to warning signs and using self-management tools and social supports contributed more to the success of DBT than the individual therapy component. Interestingly, these were the same features that set the CRP intervention apart from the NSC in the Army study. Perhaps these are the common factors of effective counseling of suicidal patients.

Indeed, these factors seem to harken back to the NSC as originally envisioned by the late Dr. Drye – a patient-driven collaboration. Dr. Drye and associates wrote: “This approach developed out of our belief that the only therapeutic contracts likely to lead to change are those developed by the patient himself, for which he will assume responsibility.” While the data presented by Dr. Drye and associates were weak, the theory behind their NSC – patient commitment – seems solid. Commitment strategies, which grew out of social psychology, are effective and heavily used in DBT, including to decrease suicidal behaviors.¹¹

Conclusion

Suicidologist Shawn Christopher Shea, MD, argues that the answer to whether or not NSCs can work is conditional on the unique combination of patient, clinician, and therapeutic relationship at play. He considers the limited data available and has warned against resolutely assuming either a pro- or anti-NSC stance. He postulates that NSCs might have the best chance at saving a life in the context of ongoing therapy with a patient with mature defenses, while in other contexts, such as with a patient with borderline personality disorder, it might prove counterproductive. Importantly, he wrote, “there is not a shred of empirical evidence that safety contracting has not been a deterrent with specific clients in the hands of specific clinicians.”

Dr. Shea describes various ways of maximizing the utility of the NSC. First, he describes that NSCs may be more effective as safety assessment tools (paying attention to both verbal and nonverbal cues) than tools to directly deter attempts. Second, NSCs may have increased utility when repeated across time to provide an understanding for how the patient typically engages in contracting. Soliciting a patient’s reasons for living also can enhance a contract’s usefulness because patients with suicidal ideation weigh reasons for living against reasons for dying in their decision-making. Finally, the sound documentation of the process of contracting not only protects against subsequent legal action but also improves the quality of the clinical care, in part by entraining the psychiatrist to incorporate key elements into the contracting process.

Returning to the clinical case, the strengths and weakness of that NSC can now be evaluated. Looking at the NSC through the eyes of Dr. Shea, the young therapeutic relationship diminishes the value of the NSC, while the relationship’s ongoing basis and the patient’s mature defenses bolster it. Dr. Shea would encourage the psychiatrist to use the NSC as an assessment tool, including assessment of ambivalence. In this case, the patient’s ambivalence about suicide comes through, but it could have been explored and expanded through explicit discussion of reasons for living. Applying the lens of Dr. Linehan, the contract is strengthened by the attention paid to social supports, while it would have been improved by specific discussion about warning signs and self-management tools.

In line with Dr. Drye’s original vision of the NSC, the degree to which the patient owns the NSC seems to be particularly crucial. In this case, the patient’s ownership of the no-suicide decision was suggested by his transparency during interview and full engagement in contracting, including identification of crisis resources. Still, the patient could have been encouraged to take additional responsibility for the NSC. One means of transferring responsibility to the patient could have been giving the patient a pen to create a written record of the contract, mobilizing and symbolizing the patient’s greater control of the process and outcome. Finally, and of utmost importance, it should be reiterated that the NSC should be only part of the assessment and planning that a psychiatrist does with a suicidal patient. While there are circumstances and strategies that augment its utility, it should not be overly relied on.
 

References

1. Weiss A. Am J Psychother. 2001;55(3):414-9.

2. Kroll J. Am J Psychiatry. 2000;157(10):1684-6.

3. Shea SC. The Practical Art of Suicide Assessment: A Guide for Mental Health Professionals and Substance Abuse Counselors. Hoboken, N.J.: John Wiley & Sons, 2011.

4. Jacobs DG et al. Practice guideline for the assessment and treatment of patients with suicidal behavior. American Psychiatric Association, 2003 Nov.

5. Lewis LM. Suicide Life Threat Behav. 2007;37(1):50-7.

6. Goin M. Psychiatr News. 2003 Jul 18;38(14):3-38.

7. Drye RC et al. Am J Psychiatry. 1973;130(2):171-4.

8. Farrow TL. J Psychiatr Ment Health Nurs. 2003 Apr;10(2):199-202.

9. Miller MC et al. Harv Rev Psychiatry. 1998;6(2):78-87.

10. Bryan CJ et al. J Affect Disord. 2017 Apr;212:64-72.

11. Pederson LD. Dialectical Behavior Therapy: A Contemporary Guide for Practitioners. Hoboken, N.J.: John Wiley & Sons, 2015.
 

Dr. Roberts is a board-certified psychiatrist in Northern Virginia, working in both the partial hospital and outpatient settings. She has a special interest in working with patients with serious mental illness and believes in the recovery model of care, in which each patient’s life goals become the focal point of their treatment. Dr. Roberts completed her psychiatry residency at George Washington University, in Washington, where she also served as the 2018-2019 chief outpatient resident. She is a native of Minnesota and earned her medical degree from the University of Minnesota, Minneapolis, in 2015. Dr. Roberts has no disclosures.




 

An elderly, retired, married African American man sought psychiatric treatment for depression and suicidal thoughts. He had a detailed, lethal suicide plan, but he had not taken any steps to carry it out.

He met DSM-5 criteria for a major depressive episode, and he described a lifelong history of recurrent depressions as well as hypomanic episodes. He was diagnosed with bipolar II disorder, and he began weekly therapy, as well as medication. Despite several static and dynamic suicide risk factors, the psychiatrist also noted that he was help seeking and future oriented. He seemed transparent during his initial appointments. He did not have access to lethal means and welcomed the psychiatrist to communicate openly with his spouse.

The patient had never attempted suicide, there was no family history of suicide, and there was no psychosis or substance use disorder present. He was able to commit to reaching out to the psychiatrist, his spouse, or emergency personnel in the case of worsening suicidal thoughts or imminent suicidal action. He remained in the outpatient setting. His suicidal ideation faded and depression receded as psychotherapy and pharmacotherapy continued.

Discussion

Depression and suicidal ideation are ubiquitous in the practice of psychiatry. Psychiatrists draw from an array of assessment and management tools when this common clinical challenge arises. Among these tools is the no-suicide contract (NSC). The NSC goes by many names, including the no-harm contract and suicide prevention contract.¹ It is a promise, verbal or written, from the patient to not attempt suicide and to tell a loved one or psychiatric provider instead.² The verbal exchange between the patient and therapist described in the case fits the widely accepted clinical definition of an NSC. The contents and implementation of NSCs vary greatly; no standard approach is taught in psychiatric training.³ The American Psychiatric Association has warned against over-reliance on them, emphasizing that they have not been proven effective. It advises that NSCs should not be used independently of other tools or outside well-established patient-provider relationships.⁴ A 2007 review of the literature on NSCs concluded that there were no data to support their effectiveness and some data that they might even cause harm.⁵

The origin of the NSC

The NSC is fairly young and its foundation arguably weak. Its evolution has been traced back to a study published in 1973 by Robert C. Drye, MD, and associates on the effectiveness of a questionnaire for the assessment of suicide risk.⁶ The questionnaire centered on the patient’s reaction to the statement, “No matter what happens, I will not kill myself, accidently or on purpose, at any time.” The authors placed special emphasis on the words “I will,” which they felt to be a stronger indicator of commitment to safety than “I promise.” The authors thought the latter statement sounded like a child’s empty reply to a demanding parent. The authors reported a 100% success rate with “approximately 600 patients” across geographic regions and clinical settings.⁷ The study group is not further described, and that the authors contend that the intervention had “complete effectiveness in evaluating suicide risk” should give pause to anyone aiming to practice evidence-based psychiatry.

The theoretical basis of the NSC has been presumed by others to be based, in part, on the principles of transactional analysis. Specifically, the suicidal patient is seen as occupying the child ego state, and the NSC is seen as a means of moving the patient into the less problematic adult ego state. It has been argued, however, that an NSC can achieve exactly the opposite. The contract can pit the patient against the clinician, entrenching the patient deeper into the child ego and, therefore, suicidal state.⁸

Michael Craig Miller, MD, and associates proposed other psychological reasons why NSCs may be counterproductive. They write, “Psychological pitfalls abound, and any of them may contribute to a contract being thoughtless, unrealistic, irrelevant, cynical, punitive, or coercive.”⁹ They postulated that the NSC grew out of and assumes the same shared decision-making inherent in any therapeutic contract – and they argue that this assumption is flawed given the legal power clinicians have over suicidal patients. While acknowledging this problematic power differential, the authors go on to urge clinicians to aim for shared decision-making and a shared burden of risk when discussing treatment with suicidal patients.

Possible NSC common factors

Psychiatry, like the rest of medicine, is increasingly practiced in an evidence-based manner. The NSC should not be excluded from this movement. To this end, a recently published, randomized study of 97 active duty Army personnel seeking emergency behavioral health evaluation compared the effectiveness of NSCs and with an alternative intervention, the crisis response plan (CRP). The CRP was chosen because it had been suggested by the Joint Commision as an alternative to the NSC, although it also has little evidence supporting its use.¹⁰

The NSC and CRP interventions of the Army study were very similar. Both included suicide risk assessment, supportive listening, provision of crisis resources, and referral to treatment. In addition, the NSC intervention included asking whether the patients could keep themselves safe at home. The CRP intervention included collaboration with the patient to identify warning signs of crisis, self-management skills, and support persons. A seemingly small but interesting difference between the two interventions was which member of the dyad, patient or clinician, created a written record of the discussion. In the NSC group, the assessor did the writing, while in the CRP group, the patient controlled the pen.

The results of the study were intriguing. Suicidal ideation declined faster in the CRP arm. Participants in the CRP arm were 76% less likely to attempt suicide over 6 months, although this effect decreased and lost statistical significance when controlling for baseline severity of suicidal ideation. Despite those promising data, the only completed suicide was in the CRP arm.

The authors compared the makeup of the CRP intervention with key components of dialectical behavior therapy (DBT). They pointed to a 2015 study by Marsha Linehan, PhD, and associates that sought to identify the active ingredients of DBT. The Linehan study indicated that attending to warning signs and using self-management tools and social supports contributed more to the success of DBT than the individual therapy component. Interestingly, these were the same features that set the CRP intervention apart from the NSC in the Army study. Perhaps these are the common factors of effective counseling of suicidal patients.

Indeed, these factors seem to harken back to the NSC as originally envisioned by the late Dr. Drye – a patient-driven collaboration. Dr. Drye and associates wrote: “This approach developed out of our belief that the only therapeutic contracts likely to lead to change are those developed by the patient himself, for which he will assume responsibility.” While the data presented by Dr. Drye and associates were weak, the theory behind their NSC – patient commitment – seems solid. Commitment strategies, which grew out of social psychology, are effective and heavily used in DBT, including to decrease suicidal behaviors.¹¹

Conclusion

Suicidologist Shawn Christopher Shea, MD, argues that the answer to whether or not NSCs can work is conditional on the unique combination of patient, clinician, and therapeutic relationship at play. He considers the limited data available and has warned against resolutely assuming either a pro- or anti-NSC stance. He postulates that NSCs might have the best chance at saving a life in the context of ongoing therapy with a patient with mature defenses, while in other contexts, such as with a patient with borderline personality disorder, it might prove counterproductive. Importantly, he wrote, “there is not a shred of empirical evidence that safety contracting has not been a deterrent with specific clients in the hands of specific clinicians.”

Dr. Shea describes various ways of maximizing the utility of the NSC. First, he describes that NSCs may be more effective as safety assessment tools (paying attention to both verbal and nonverbal cues) than tools to directly deter attempts. Second, NSCs may have increased utility when repeated across time to provide an understanding for how the patient typically engages in contracting. Soliciting a patient’s reasons for living also can enhance a contract’s usefulness because patients with suicidal ideation weigh reasons for living against reasons for dying in their decision-making. Finally, the sound documentation of the process of contracting not only protects against subsequent legal action but also improves the quality of the clinical care, in part by entraining the psychiatrist to incorporate key elements into the contracting process.

Returning to the clinical case, the strengths and weakness of that NSC can now be evaluated. Looking at the NSC through the eyes of Dr. Shea, the young therapeutic relationship diminishes the value of the NSC, while the relationship’s ongoing basis and the patient’s mature defenses bolster it. Dr. Shea would encourage the psychiatrist to use the NSC as an assessment tool, including assessment of ambivalence. In this case, the patient’s ambivalence about suicide comes through, but it could have been explored and expanded through explicit discussion of reasons for living. Applying the lens of Dr. Linehan, the contract is strengthened by the attention paid to social supports, while it would have been improved by specific discussion about warning signs and self-management tools.

In line with Dr. Drye’s original vision of the NSC, the degree to which the patient owns the NSC seems to be particularly crucial. In this case, the patient’s ownership of the no-suicide decision was suggested by his transparency during interview and full engagement in contracting, including identification of crisis resources. Still, the patient could have been encouraged to take additional responsibility for the NSC. One means of transferring responsibility to the patient could have been giving the patient a pen to create a written record of the contract, mobilizing and symbolizing the patient’s greater control of the process and outcome. Finally, and of utmost importance, it should be reiterated that the NSC should be only part of the assessment and planning that a psychiatrist does with a suicidal patient. While there are circumstances and strategies that augment its utility, it should not be overly relied on.
 

References

1. Weiss A. Am J Psychother. 2001;55(3):414-9.

2. Kroll J. Am J Psychiatry. 2000;157(10):1684-6.

3. Shea SC. The Practical Art of Suicide Assessment: A Guide for Mental Health Professionals and Substance Abuse Counselors. Hoboken, N.J.: John Wiley & Sons, 2011.

4. Jacobs DG et al. Practice guideline for the assessment and treatment of patients with suicidal behavior. American Psychiatric Association, 2003 Nov.

5. Lewis LM. Suicide Life Threat Behav. 2007;37(1):50-7.

6. Goin M. Psychiatr News. 2003 Jul 18;38(14):3-38.

7. Drye RC et al. Am J Psychiatry. 1973;130(2):171-4.

8. Farrow TL. J Psychiatr Ment Health Nurs. 2003 Apr;10(2):199-202.

9. Miller MC et al. Harv Rev Psychiatry. 1998;6(2):78-87.

10. Bryan CJ et al. J Affect Disord. 2017 Apr;212:64-72.

11. Pederson LD. Dialectical Behavior Therapy: A Contemporary Guide for Practitioners. Hoboken, N.J.: John Wiley & Sons, 2015.
 

Dr. Roberts is a board-certified psychiatrist in Northern Virginia, working in both the partial hospital and outpatient settings. She has a special interest in working with patients with serious mental illness and believes in the recovery model of care, in which each patient’s life goals become the focal point of their treatment. Dr. Roberts completed her psychiatry residency at George Washington University, in Washington, where she also served as the 2018-2019 chief outpatient resident. She is a native of Minnesota and earned her medical degree from the University of Minnesota, Minneapolis, in 2015. Dr. Roberts has no disclosures.




 

An elderly, retired, married African American man sought psychiatric treatment for depression and suicidal thoughts. He had a detailed, lethal suicide plan, but he had not taken any steps to carry it out.

He met DSM-5 criteria for a major depressive episode, and he described a lifelong history of recurrent depressions as well as hypomanic episodes. He was diagnosed with bipolar II disorder, and he began weekly therapy, as well as medication. Despite several static and dynamic suicide risk factors, the psychiatrist also noted that he was help seeking and future oriented. He seemed transparent during his initial appointments. He did not have access to lethal means and welcomed the psychiatrist to communicate openly with his spouse.

The patient had never attempted suicide, there was no family history of suicide, and there was no psychosis or substance use disorder present. He was able to commit to reaching out to the psychiatrist, his spouse, or emergency personnel in the case of worsening suicidal thoughts or imminent suicidal action. He remained in the outpatient setting. His suicidal ideation faded and depression receded as psychotherapy and pharmacotherapy continued.

Discussion

Depression and suicidal ideation are ubiquitous in the practice of psychiatry. Psychiatrists draw from an array of assessment and management tools when this common clinical challenge arises. Among these tools is the no-suicide contract (NSC). The NSC goes by many names, including the no-harm contract and suicide prevention contract.¹ It is a promise, verbal or written, from the patient to not attempt suicide and to tell a loved one or psychiatric provider instead.² The verbal exchange between the patient and therapist described in the case fits the widely accepted clinical definition of an NSC. The contents and implementation of NSCs vary greatly; no standard approach is taught in psychiatric training.³ The American Psychiatric Association has warned against over-reliance on them, emphasizing that they have not been proven effective. It advises that NSCs should not be used independently of other tools or outside well-established patient-provider relationships.⁴ A 2007 review of the literature on NSCs concluded that there were no data to support their effectiveness and some data that they might even cause harm.⁵

The origin of the NSC

The NSC is fairly young and its foundation arguably weak. Its evolution has been traced back to a study published in 1973 by Robert C. Drye, MD, and associates on the effectiveness of a questionnaire for the assessment of suicide risk.⁶ The questionnaire centered on the patient’s reaction to the statement, “No matter what happens, I will not kill myself, accidently or on purpose, at any time.” The authors placed special emphasis on the words “I will,” which they felt to be a stronger indicator of commitment to safety than “I promise.” The authors thought the latter statement sounded like a child’s empty reply to a demanding parent. The authors reported a 100% success rate with “approximately 600 patients” across geographic regions and clinical settings.⁷ The study group is not further described, and that the authors contend that the intervention had “complete effectiveness in evaluating suicide risk” should give pause to anyone aiming to practice evidence-based psychiatry.

The theoretical basis of the NSC has been presumed by others to be based, in part, on the principles of transactional analysis. Specifically, the suicidal patient is seen as occupying the child ego state, and the NSC is seen as a means of moving the patient into the less problematic adult ego state. It has been argued, however, that an NSC can achieve exactly the opposite. The contract can pit the patient against the clinician, entrenching the patient deeper into the child ego and, therefore, suicidal state.⁸

Michael Craig Miller, MD, and associates proposed other psychological reasons why NSCs may be counterproductive. They write, “Psychological pitfalls abound, and any of them may contribute to a contract being thoughtless, unrealistic, irrelevant, cynical, punitive, or coercive.”⁹ They postulated that the NSC grew out of and assumes the same shared decision-making inherent in any therapeutic contract – and they argue that this assumption is flawed given the legal power clinicians have over suicidal patients. While acknowledging this problematic power differential, the authors go on to urge clinicians to aim for shared decision-making and a shared burden of risk when discussing treatment with suicidal patients.

Possible NSC common factors

Psychiatry, like the rest of medicine, is increasingly practiced in an evidence-based manner. The NSC should not be excluded from this movement. To this end, a recently published, randomized study of 97 active duty Army personnel seeking emergency behavioral health evaluation compared the effectiveness of NSCs and with an alternative intervention, the crisis response plan (CRP). The CRP was chosen because it had been suggested by the Joint Commision as an alternative to the NSC, although it also has little evidence supporting its use.¹⁰

The NSC and CRP interventions of the Army study were very similar. Both included suicide risk assessment, supportive listening, provision of crisis resources, and referral to treatment. In addition, the NSC intervention included asking whether the patients could keep themselves safe at home. The CRP intervention included collaboration with the patient to identify warning signs of crisis, self-management skills, and support persons. A seemingly small but interesting difference between the two interventions was which member of the dyad, patient or clinician, created a written record of the discussion. In the NSC group, the assessor did the writing, while in the CRP group, the patient controlled the pen.

The results of the study were intriguing. Suicidal ideation declined faster in the CRP arm. Participants in the CRP arm were 76% less likely to attempt suicide over 6 months, although this effect decreased and lost statistical significance when controlling for baseline severity of suicidal ideation. Despite those promising data, the only completed suicide was in the CRP arm.

The authors compared the makeup of the CRP intervention with key components of dialectical behavior therapy (DBT). They pointed to a 2015 study by Marsha Linehan, PhD, and associates that sought to identify the active ingredients of DBT. The Linehan study indicated that attending to warning signs and using self-management tools and social supports contributed more to the success of DBT than the individual therapy component. Interestingly, these were the same features that set the CRP intervention apart from the NSC in the Army study. Perhaps these are the common factors of effective counseling of suicidal patients.

Indeed, these factors seem to harken back to the NSC as originally envisioned by the late Dr. Drye – a patient-driven collaboration. Dr. Drye and associates wrote: “This approach developed out of our belief that the only therapeutic contracts likely to lead to change are those developed by the patient himself, for which he will assume responsibility.” While the data presented by Dr. Drye and associates were weak, the theory behind their NSC – patient commitment – seems solid. Commitment strategies, which grew out of social psychology, are effective and heavily used in DBT, including to decrease suicidal behaviors.¹¹

Conclusion

Suicidologist Shawn Christopher Shea, MD, argues that the answer to whether or not NSCs can work is conditional on the unique combination of patient, clinician, and therapeutic relationship at play. He considers the limited data available and has warned against resolutely assuming either a pro- or anti-NSC stance. He postulates that NSCs might have the best chance at saving a life in the context of ongoing therapy with a patient with mature defenses, while in other contexts, such as with a patient with borderline personality disorder, it might prove counterproductive. Importantly, he wrote, “there is not a shred of empirical evidence that safety contracting has not been a deterrent with specific clients in the hands of specific clinicians.”

Dr. Shea describes various ways of maximizing the utility of the NSC. First, he describes that NSCs may be more effective as safety assessment tools (paying attention to both verbal and nonverbal cues) than tools to directly deter attempts. Second, NSCs may have increased utility when repeated across time to provide an understanding for how the patient typically engages in contracting. Soliciting a patient’s reasons for living also can enhance a contract’s usefulness because patients with suicidal ideation weigh reasons for living against reasons for dying in their decision-making. Finally, the sound documentation of the process of contracting not only protects against subsequent legal action but also improves the quality of the clinical care, in part by entraining the psychiatrist to incorporate key elements into the contracting process.

Returning to the clinical case, the strengths and weakness of that NSC can now be evaluated. Looking at the NSC through the eyes of Dr. Shea, the young therapeutic relationship diminishes the value of the NSC, while the relationship’s ongoing basis and the patient’s mature defenses bolster it. Dr. Shea would encourage the psychiatrist to use the NSC as an assessment tool, including assessment of ambivalence. In this case, the patient’s ambivalence about suicide comes through, but it could have been explored and expanded through explicit discussion of reasons for living. Applying the lens of Dr. Linehan, the contract is strengthened by the attention paid to social supports, while it would have been improved by specific discussion about warning signs and self-management tools.

In line with Dr. Drye’s original vision of the NSC, the degree to which the patient owns the NSC seems to be particularly crucial. In this case, the patient’s ownership of the no-suicide decision was suggested by his transparency during interview and full engagement in contracting, including identification of crisis resources. Still, the patient could have been encouraged to take additional responsibility for the NSC. One means of transferring responsibility to the patient could have been giving the patient a pen to create a written record of the contract, mobilizing and symbolizing the patient’s greater control of the process and outcome. Finally, and of utmost importance, it should be reiterated that the NSC should be only part of the assessment and planning that a psychiatrist does with a suicidal patient. While there are circumstances and strategies that augment its utility, it should not be overly relied on.
 

References

1. Weiss A. Am J Psychother. 2001;55(3):414-9.

2. Kroll J. Am J Psychiatry. 2000;157(10):1684-6.

3. Shea SC. The Practical Art of Suicide Assessment: A Guide for Mental Health Professionals and Substance Abuse Counselors. Hoboken, N.J.: John Wiley & Sons, 2011.

4. Jacobs DG et al. Practice guideline for the assessment and treatment of patients with suicidal behavior. American Psychiatric Association, 2003 Nov.

5. Lewis LM. Suicide Life Threat Behav. 2007;37(1):50-7.

6. Goin M. Psychiatr News. 2003 Jul 18;38(14):3-38.

7. Drye RC et al. Am J Psychiatry. 1973;130(2):171-4.

8. Farrow TL. J Psychiatr Ment Health Nurs. 2003 Apr;10(2):199-202.

9. Miller MC et al. Harv Rev Psychiatry. 1998;6(2):78-87.

10. Bryan CJ et al. J Affect Disord. 2017 Apr;212:64-72.

11. Pederson LD. Dialectical Behavior Therapy: A Contemporary Guide for Practitioners. Hoboken, N.J.: John Wiley & Sons, 2015.
 

Dr. Roberts is a board-certified psychiatrist in Northern Virginia, working in both the partial hospital and outpatient settings. She has a special interest in working with patients with serious mental illness and believes in the recovery model of care, in which each patient’s life goals become the focal point of their treatment. Dr. Roberts completed her psychiatry residency at George Washington University, in Washington, where she also served as the 2018-2019 chief outpatient resident. She is a native of Minnesota and earned her medical degree from the University of Minnesota, Minneapolis, in 2015. Dr. Roberts has no disclosures.




 

The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.

EHStock/iStock/Getty Images

In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.

After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.

The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.

The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.

“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.

“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.

“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.

Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.

“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”

Dr. Bohon had no relevant financial conflicts to disclose.

The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.

EHStock/iStock/Getty Images

In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.

After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.

The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.

The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.

“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.

“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.

“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.

Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.

“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”

Dr. Bohon had no relevant financial conflicts to disclose.

The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.

EHStock/iStock/Getty Images

In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.

After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.

The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.

The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.

“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.

“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.

“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.

Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.

“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”

Dr. Bohon had no relevant financial conflicts to disclose.

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

A version of this article originally appeared on Medscape.com.

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

A version of this article originally appeared on Medscape.com.

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

A version of this article originally appeared on Medscape.com.