Kehinde Eniola, MD, MPH

PRACTICE CHANGER
Consider treatment with bright light therapy, alone or in combination with fluoxetine, for patients with nonseasonal major depressive disorder.¹

Strength of Recommendation
B: Based on a single moderate-quality randomized controlled trial.¹

A 38-year-old woman recently diagnosed with major depressive disorder (MDD) without a seasonal pattern presents to discuss treatment options. Her Hamilton Depression Rating Scale (HAM-D) score is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in five adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective firstline pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with firstline or secondline drugs.² In addition, pharmaco­logic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N = 620) demonstrated the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD but found no benefit to light used as monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted less than four weeks.

In a five-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline (50 mg/d) or sham light treatment (using a dim red light) plus sertraline (50 mg/d). The investigators found a statistically significant reduction in depression score in the active treatment group compared to the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the seven atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Continue for the study summary >>

STUDY SUMMARY
Light therapy improves nonseasonal depression
This latest study was an eight-week, randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19 to 60) from outpatient psychiatry clinics who had a diagnosis of MDD (diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least two weeks prior to the first visit; they were subsequently monitored for one week to identify spontaneous responders and give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10 PM and 8 AM daily).

The investigators randomly assigned patients to one of four treatment groups:
• Active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill
• Fluoxetine (20 mg/d) plus sham light therapy
• Placebo pills with sham light therapy; or
• Combined active light therapy with fluoxetine (20 mg/d).

Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat. Adherence was assessed through review of patients’ daily logs of device treatment times and through pill counts.

The primary outcome at eight weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥ 50% reduction in MADRS score) and remission (MADRS score ≤ 10) at the final eighth-week visit. MADRS scoring was used because of its sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

At the end of eight weeks, the mean changes in MADRS scores from baseline were: light monotherapy, 13.4; fluoxetine monotherapy, 8.8; combination therapy, 16.9; and placebo, 6.5. The improvement was significant in the light monotherapy treatment group and in the combination therapy group, compared with the placebo group, and in the combination group, compared with the fluoxetine treatment group; improvement was not significant for the fluoxetine treatment group compared with the placebo group, however.

The treatment response (≥ 50% MADRS improvement) rate was highest in the combination treatment group (75.9%), followed by light monotherapy (50%), placebo (33.3%), and fluoxetine monotherapy (29%). There was a significant response effect for the combination versus placebo treatment group.

Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively). Combination therapy was superior to placebo in treatment response (≥ 50% reduction in the MADRS score) and remission (MADRS ≤ 10), with numbers needed to treat of 2.4 and 3.5, respectively.

By the end of the eight-week study period, 16 of 122 patients had dropped out. Two reported lack of efficacy, five reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew ­consent.

WHAT’S NEW
New evidence on a not-so-new treatment
We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious for increasing the remission rate of nonseasonal MDD.

Continue for caveats >>

CAVEATS
Variables may have affected results
Among the study’s limitations: use of a single SSRI (other, more potent SSRIs might work better); location (southern Canada; benefits may differ in regions farther south); and exclusion of pregnant and breastfeeding women from the study population.

Furthermore, the trial duration was relatively short, and the investigators did not attain their preplanned sample size for the study. This limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

CHALLENGES TO IMPLEMENTATION
Commercial insurance doesn’t usually cover light therapy
Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹⁰ Since few studies have tested light therapy for nonseasonal MDD, uncertainty remains about patient selection, as well as optimal dose, timing, and duration in the management of nonseasonal MDD.¹¹ Although the associated risks are minimal, bright light therapy can lead to mania or hypomania; clinicians need to monitor for such effects when initiating therapy.³

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which are available in medical supply stores and online, ranges from $118 to $237.^4,11 However, such de­vices are reusable, making the amortized cost almost negligible and perhaps negating this concern.¹²

REFERENCES
1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63.
2. Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci. 2011;342:324-330.
3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed July 5, 2016.
4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. New York, NY: Cambridge University Press; 2009. www.ubcmood.ca/sad/SAD%20resources%20package%202009.pdf. Accessed July 5, 2016.
5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;2:CD004050.
6. Martiny K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatr Scand Suppl. 2004;425:7-28.
7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005;112:117-125.
8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
10. Oldham MA, Ciraulo DA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord. 2014;16(3). Epub 2014 Jun 26.
11. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disorders and depression in older adults. Clin Geriatr. 2008;16:25-31.
12. Kripke DF. A breakthrough treatment for major depression. J Clin Psychiatry. 2015;76:e660-e661.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(7):486-488.

PRACTICE CHANGER
Consider treatment with bright light therapy, alone or in combination with fluoxetine, for patients with nonseasonal major depressive disorder.¹

Strength of Recommendation
B: Based on a single moderate-quality randomized controlled trial.¹

A 38-year-old woman recently diagnosed with major depressive disorder (MDD) without a seasonal pattern presents to discuss treatment options. Her Hamilton Depression Rating Scale (HAM-D) score is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in five adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective firstline pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with firstline or secondline drugs.² In addition, pharmaco­logic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N = 620) demonstrated the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD but found no benefit to light used as monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted less than four weeks.

In a five-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline (50 mg/d) or sham light treatment (using a dim red light) plus sertraline (50 mg/d). The investigators found a statistically significant reduction in depression score in the active treatment group compared to the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the seven atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Continue for the study summary >>

STUDY SUMMARY
Light therapy improves nonseasonal depression
This latest study was an eight-week, randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19 to 60) from outpatient psychiatry clinics who had a diagnosis of MDD (diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least two weeks prior to the first visit; they were subsequently monitored for one week to identify spontaneous responders and give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10 PM and 8 AM daily).

The investigators randomly assigned patients to one of four treatment groups:
• Active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill
• Fluoxetine (20 mg/d) plus sham light therapy
• Placebo pills with sham light therapy; or
• Combined active light therapy with fluoxetine (20 mg/d).

Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat. Adherence was assessed through review of patients’ daily logs of device treatment times and through pill counts.

The primary outcome at eight weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥ 50% reduction in MADRS score) and remission (MADRS score ≤ 10) at the final eighth-week visit. MADRS scoring was used because of its sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

At the end of eight weeks, the mean changes in MADRS scores from baseline were: light monotherapy, 13.4; fluoxetine monotherapy, 8.8; combination therapy, 16.9; and placebo, 6.5. The improvement was significant in the light monotherapy treatment group and in the combination therapy group, compared with the placebo group, and in the combination group, compared with the fluoxetine treatment group; improvement was not significant for the fluoxetine treatment group compared with the placebo group, however.

The treatment response (≥ 50% MADRS improvement) rate was highest in the combination treatment group (75.9%), followed by light monotherapy (50%), placebo (33.3%), and fluoxetine monotherapy (29%). There was a significant response effect for the combination versus placebo treatment group.

Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively). Combination therapy was superior to placebo in treatment response (≥ 50% reduction in the MADRS score) and remission (MADRS ≤ 10), with numbers needed to treat of 2.4 and 3.5, respectively.

By the end of the eight-week study period, 16 of 122 patients had dropped out. Two reported lack of efficacy, five reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew ­consent.

WHAT’S NEW
New evidence on a not-so-new treatment
We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious for increasing the remission rate of nonseasonal MDD.

Continue for caveats >>

CAVEATS
Variables may have affected results
Among the study’s limitations: use of a single SSRI (other, more potent SSRIs might work better); location (southern Canada; benefits may differ in regions farther south); and exclusion of pregnant and breastfeeding women from the study population.

Furthermore, the trial duration was relatively short, and the investigators did not attain their preplanned sample size for the study. This limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

CHALLENGES TO IMPLEMENTATION
Commercial insurance doesn’t usually cover light therapy
Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹⁰ Since few studies have tested light therapy for nonseasonal MDD, uncertainty remains about patient selection, as well as optimal dose, timing, and duration in the management of nonseasonal MDD.¹¹ Although the associated risks are minimal, bright light therapy can lead to mania or hypomania; clinicians need to monitor for such effects when initiating therapy.³

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which are available in medical supply stores and online, ranges from $118 to $237.^4,11 However, such de­vices are reusable, making the amortized cost almost negligible and perhaps negating this concern.¹²

REFERENCES
1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63.
2. Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci. 2011;342:324-330.
3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed July 5, 2016.
4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. New York, NY: Cambridge University Press; 2009. www.ubcmood.ca/sad/SAD%20resources%20package%202009.pdf. Accessed July 5, 2016.
5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;2:CD004050.
6. Martiny K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatr Scand Suppl. 2004;425:7-28.
7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005;112:117-125.
8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
10. Oldham MA, Ciraulo DA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord. 2014;16(3). Epub 2014 Jun 26.
11. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disorders and depression in older adults. Clin Geriatr. 2008;16:25-31.
12. Kripke DF. A breakthrough treatment for major depression. J Clin Psychiatry. 2015;76:e660-e661.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(7):486-488.

PRACTICE CHANGER
Consider treatment with bright light therapy, alone or in combination with fluoxetine, for patients with nonseasonal major depressive disorder.¹

Strength of Recommendation
B: Based on a single moderate-quality randomized controlled trial.¹

A 38-year-old woman recently diagnosed with major depressive disorder (MDD) without a seasonal pattern presents to discuss treatment options. Her Hamilton Depression Rating Scale (HAM-D) score is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in five adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective firstline pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with firstline or secondline drugs.² In addition, pharmaco­logic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N = 620) demonstrated the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD but found no benefit to light used as monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted less than four weeks.

In a five-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline (50 mg/d) or sham light treatment (using a dim red light) plus sertraline (50 mg/d). The investigators found a statistically significant reduction in depression score in the active treatment group compared to the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the seven atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Continue for the study summary >>

STUDY SUMMARY
Light therapy improves nonseasonal depression
This latest study was an eight-week, randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19 to 60) from outpatient psychiatry clinics who had a diagnosis of MDD (diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least two weeks prior to the first visit; they were subsequently monitored for one week to identify spontaneous responders and give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10 PM and 8 AM daily).

The investigators randomly assigned patients to one of four treatment groups:
• Active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill
• Fluoxetine (20 mg/d) plus sham light therapy
• Placebo pills with sham light therapy; or
• Combined active light therapy with fluoxetine (20 mg/d).

Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat. Adherence was assessed through review of patients’ daily logs of device treatment times and through pill counts.

The primary outcome at eight weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥ 50% reduction in MADRS score) and remission (MADRS score ≤ 10) at the final eighth-week visit. MADRS scoring was used because of its sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

At the end of eight weeks, the mean changes in MADRS scores from baseline were: light monotherapy, 13.4; fluoxetine monotherapy, 8.8; combination therapy, 16.9; and placebo, 6.5. The improvement was significant in the light monotherapy treatment group and in the combination therapy group, compared with the placebo group, and in the combination group, compared with the fluoxetine treatment group; improvement was not significant for the fluoxetine treatment group compared with the placebo group, however.

The treatment response (≥ 50% MADRS improvement) rate was highest in the combination treatment group (75.9%), followed by light monotherapy (50%), placebo (33.3%), and fluoxetine monotherapy (29%). There was a significant response effect for the combination versus placebo treatment group.

Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively). Combination therapy was superior to placebo in treatment response (≥ 50% reduction in the MADRS score) and remission (MADRS ≤ 10), with numbers needed to treat of 2.4 and 3.5, respectively.

By the end of the eight-week study period, 16 of 122 patients had dropped out. Two reported lack of efficacy, five reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew ­consent.

WHAT’S NEW
New evidence on a not-so-new treatment
We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious for increasing the remission rate of nonseasonal MDD.

Continue for caveats >>

CAVEATS
Variables may have affected results
Among the study’s limitations: use of a single SSRI (other, more potent SSRIs might work better); location (southern Canada; benefits may differ in regions farther south); and exclusion of pregnant and breastfeeding women from the study population.

Furthermore, the trial duration was relatively short, and the investigators did not attain their preplanned sample size for the study. This limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

CHALLENGES TO IMPLEMENTATION
Commercial insurance doesn’t usually cover light therapy
Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹⁰ Since few studies have tested light therapy for nonseasonal MDD, uncertainty remains about patient selection, as well as optimal dose, timing, and duration in the management of nonseasonal MDD.¹¹ Although the associated risks are minimal, bright light therapy can lead to mania or hypomania; clinicians need to monitor for such effects when initiating therapy.³

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which are available in medical supply stores and online, ranges from $118 to $237.^4,11 However, such de­vices are reusable, making the amortized cost almost negligible and perhaps negating this concern.¹²

REFERENCES
1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63.
2. Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci. 2011;342:324-330.
3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed July 5, 2016.
4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. New York, NY: Cambridge University Press; 2009. www.ubcmood.ca/sad/SAD%20resources%20package%202009.pdf. Accessed July 5, 2016.
5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;2:CD004050.
6. Martiny K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatr Scand Suppl. 2004;425:7-28.
7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005;112:117-125.
8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
10. Oldham MA, Ciraulo DA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord. 2014;16(3). Epub 2014 Jun 26.
11. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disorders and depression in older adults. Clin Geriatr. 2008;16:25-31.
12. Kripke DF. A breakthrough treatment for major depression. J Clin Psychiatry. 2015;76:e660-e661.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(7):486-488.

Illustrative Case

A 38-year-old woman recently diagnosed with MDD without a seasonal pattern comes to see you for her treatment options. Her Hamilton Depression Rating Scale (HAM-D) is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in 5 adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective first-line pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with first- or second-line drugs.² In addition, pharmacologic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N=620) showed the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD, but found no benefit to light used as a monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted fewer than 4 weeks.

In a 5-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline 50 mg daily or sham light treatment (using a dim red light) plus sertraline 50 mg daily. The investigators found a statistically significant larger reduction in depression score in the active treatment group than in the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the 7 atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Study Summary 

Light therapy improves depression without a seasonal component

This latest study was an 8-week randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19-60 years) from outpatient psychiatry clinics with a diagnosis of MDD (as diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least 2 weeks prior to the first visit and were subsequently monitored for one week to identify spontaneous responders and to give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10:00 pm and 8:00 am daily).

The investigators randomly assigned patients to one of 4 treatment groups: active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill; fluoxetine 20 mg/d plus sham light therapy; placebo pills with sham light therapy; and combined active light therapy with fluoxetine 20 mg daily. Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat.

The investigators monitored patients for adherence to active and sham treatment by review of their daily logs of device treatment times. Pill counts were used to assess medication adherence. The primary outcome at 8 weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥50% MADRS score reduction) and remission (≤10 MADRS score) at the final 8th-week visit. MADRS scoring was used because of its higher sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

Seventy-six percent of patients treated with fluoxetine and light therapy saw at least a 50% improvement in their depression scores.

At the end of 8 weeks, the mean (standard deviation [SD]) changes in MADRS scores from baseline were: light monotherapy 13.4 (7.5), fluoxetine monotherapy 8.8 (9.9), combination therapy 16.9 (9.2), and placebo 6.5 (9.6). The improvement was significant in the light monotherapy treatment group vs the placebo group (P=.006), in the combination treatment group vs the vs placebo group (P<.001), and in the combination group vs the fluoxetine treatment group (P=.02), but not for the fluoxetine treatment group vs the placebo group (P=.32). The effect sizes vs placebo were: fluoxetine, d=0.24 (95% confidence interval [CI], −0.27 to 0.74); light monotherapy, 0.80 (95% CI, 0.28 to 1.31); and combination therapy, 1.11 (95% CI, 0.54 to 1.64). Effect sizes of more than 0.8 are often considered large.¹⁰

The treatment response (≥50% MADRS improvement) rate was highest in the combination treatment group (75.9%) with response rates to light monotherapy, placebo, and fluoxetine monotherapy of 50%, 33.3%, and 29%, respectively. There was a significant response effect for the combination vs placebo treatment group (P=.005). Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively) with a significant effect for the combination vs placebo treatment group (P=.02).

Combination therapy was superior to placebo in treatment response (≥50% reduction in the MADRS score) and remission (MADRS ≤10) with numbers needed to treat of 2.4 (95% CI, 1.6-5.8) and 3.5 (95% CI, 2.0-29.9), respectively.

By the end of the 8-week study period, 16 of 122 patients had dropped out; 2 reported lack of efficacy, 5 reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew consent.

What’s New? 

New evidence on a not-so-new treatment

We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious in increasing the remission rate of nonseasonal MDD.

Caveats 

Choice of SSRI, geography, and trial duration may have affected results

A single SSRI (fluoxetine) was used in this study; other more potent SSRIs might work better. This study was conducted in southern Canada, and light therapy may not demonstrate as large a benefit in regions located farther south. The study excluded pregnant and breastfeeding women.

The trial duration was relatively short, and the investigators did not attain their pre-planned sample size for the study, which limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

Also, it’s worth noting that there were trends for some adverse events (nausea, heartburn, weight gain, agitation, sexual dysfunction, and skin rash) to occur less frequently in the combination group than in the fluoxetine monotherapy group. Possible explanations are that the study had inadequate power, that the sham treatment did not adequately blind patients, or that light therapy can ameliorate some of the adverse effects of fluoxetine.

We now have evidence that bright light therapy, alone or in combination with fluoxetine, is efficacious in increasing the remission rate of nonseasonal major depressive disorder.

Challenges to Implementation

Commercial insurance doesn’t usually cover light therapy

Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹¹ Since only a few studies have tested light therapy for nonseasonal MDD, significant uncertainty remains about patient selection, as well as optimal dose, timing, and duration of light therapy in the management of nonseasonal MDD.¹² Although the risks associated with bright light therapy are minimal, the therapy can lead to mania or hypomania,³ so clinicians need to monitor for such effects when initiating therapy.

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which can be found in medical supply stores and online outlets, ranges between $118 and $237.^4,12 However, such devices are reusable, making the amortized cost almost negligible.¹³

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative Case

A 38-year-old woman recently diagnosed with MDD without a seasonal pattern comes to see you for her treatment options. Her Hamilton Depression Rating Scale (HAM-D) is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in 5 adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective first-line pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with first- or second-line drugs.² In addition, pharmacologic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N=620) showed the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD, but found no benefit to light used as a monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted fewer than 4 weeks.

In a 5-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline 50 mg daily or sham light treatment (using a dim red light) plus sertraline 50 mg daily. The investigators found a statistically significant larger reduction in depression score in the active treatment group than in the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the 7 atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Study Summary 

Light therapy improves depression without a seasonal component

This latest study was an 8-week randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19-60 years) from outpatient psychiatry clinics with a diagnosis of MDD (as diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least 2 weeks prior to the first visit and were subsequently monitored for one week to identify spontaneous responders and to give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10:00 pm and 8:00 am daily).

The investigators randomly assigned patients to one of 4 treatment groups: active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill; fluoxetine 20 mg/d plus sham light therapy; placebo pills with sham light therapy; and combined active light therapy with fluoxetine 20 mg daily. Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat.

The investigators monitored patients for adherence to active and sham treatment by review of their daily logs of device treatment times. Pill counts were used to assess medication adherence. The primary outcome at 8 weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥50% MADRS score reduction) and remission (≤10 MADRS score) at the final 8th-week visit. MADRS scoring was used because of its higher sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

Seventy-six percent of patients treated with fluoxetine and light therapy saw at least a 50% improvement in their depression scores.

At the end of 8 weeks, the mean (standard deviation [SD]) changes in MADRS scores from baseline were: light monotherapy 13.4 (7.5), fluoxetine monotherapy 8.8 (9.9), combination therapy 16.9 (9.2), and placebo 6.5 (9.6). The improvement was significant in the light monotherapy treatment group vs the placebo group (P=.006), in the combination treatment group vs the vs placebo group (P<.001), and in the combination group vs the fluoxetine treatment group (P=.02), but not for the fluoxetine treatment group vs the placebo group (P=.32). The effect sizes vs placebo were: fluoxetine, d=0.24 (95% confidence interval [CI], −0.27 to 0.74); light monotherapy, 0.80 (95% CI, 0.28 to 1.31); and combination therapy, 1.11 (95% CI, 0.54 to 1.64). Effect sizes of more than 0.8 are often considered large.¹⁰

The treatment response (≥50% MADRS improvement) rate was highest in the combination treatment group (75.9%) with response rates to light monotherapy, placebo, and fluoxetine monotherapy of 50%, 33.3%, and 29%, respectively. There was a significant response effect for the combination vs placebo treatment group (P=.005). Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively) with a significant effect for the combination vs placebo treatment group (P=.02).

Combination therapy was superior to placebo in treatment response (≥50% reduction in the MADRS score) and remission (MADRS ≤10) with numbers needed to treat of 2.4 (95% CI, 1.6-5.8) and 3.5 (95% CI, 2.0-29.9), respectively.

By the end of the 8-week study period, 16 of 122 patients had dropped out; 2 reported lack of efficacy, 5 reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew consent.

What’s New? 

New evidence on a not-so-new treatment

We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious in increasing the remission rate of nonseasonal MDD.

Caveats 

Choice of SSRI, geography, and trial duration may have affected results

A single SSRI (fluoxetine) was used in this study; other more potent SSRIs might work better. This study was conducted in southern Canada, and light therapy may not demonstrate as large a benefit in regions located farther south. The study excluded pregnant and breastfeeding women.

The trial duration was relatively short, and the investigators did not attain their pre-planned sample size for the study, which limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

Also, it’s worth noting that there were trends for some adverse events (nausea, heartburn, weight gain, agitation, sexual dysfunction, and skin rash) to occur less frequently in the combination group than in the fluoxetine monotherapy group. Possible explanations are that the study had inadequate power, that the sham treatment did not adequately blind patients, or that light therapy can ameliorate some of the adverse effects of fluoxetine.

We now have evidence that bright light therapy, alone or in combination with fluoxetine, is efficacious in increasing the remission rate of nonseasonal major depressive disorder.

Challenges to Implementation

Commercial insurance doesn’t usually cover light therapy

Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹¹ Since only a few studies have tested light therapy for nonseasonal MDD, significant uncertainty remains about patient selection, as well as optimal dose, timing, and duration of light therapy in the management of nonseasonal MDD.¹² Although the risks associated with bright light therapy are minimal, the therapy can lead to mania or hypomania,³ so clinicians need to monitor for such effects when initiating therapy.

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which can be found in medical supply stores and online outlets, ranges between $118 and $237.^4,12 However, such devices are reusable, making the amortized cost almost negligible.¹³

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative Case

A 38-year-old woman recently diagnosed with MDD without a seasonal pattern comes to see you for her treatment options. Her Hamilton Depression Rating Scale (HAM-D) is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in 5 adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective first-line pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with first- or second-line drugs.² In addition, pharmacologic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N=620) showed the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD, but found no benefit to light used as a monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted fewer than 4 weeks.

In a 5-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline 50 mg daily or sham light treatment (using a dim red light) plus sertraline 50 mg daily. The investigators found a statistically significant larger reduction in depression score in the active treatment group than in the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the 7 atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Study Summary 

Light therapy improves depression without a seasonal component

This latest study was an 8-week randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19-60 years) from outpatient psychiatry clinics with a diagnosis of MDD (as diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least 2 weeks prior to the first visit and were subsequently monitored for one week to identify spontaneous responders and to give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10:00 pm and 8:00 am daily).

The investigators randomly assigned patients to one of 4 treatment groups: active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill; fluoxetine 20 mg/d plus sham light therapy; placebo pills with sham light therapy; and combined active light therapy with fluoxetine 20 mg daily. Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat.

The investigators monitored patients for adherence to active and sham treatment by review of their daily logs of device treatment times. Pill counts were used to assess medication adherence. The primary outcome at 8 weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥50% MADRS score reduction) and remission (≤10 MADRS score) at the final 8th-week visit. MADRS scoring was used because of its higher sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

Seventy-six percent of patients treated with fluoxetine and light therapy saw at least a 50% improvement in their depression scores.

At the end of 8 weeks, the mean (standard deviation [SD]) changes in MADRS scores from baseline were: light monotherapy 13.4 (7.5), fluoxetine monotherapy 8.8 (9.9), combination therapy 16.9 (9.2), and placebo 6.5 (9.6). The improvement was significant in the light monotherapy treatment group vs the placebo group (P=.006), in the combination treatment group vs the vs placebo group (P<.001), and in the combination group vs the fluoxetine treatment group (P=.02), but not for the fluoxetine treatment group vs the placebo group (P=.32). The effect sizes vs placebo were: fluoxetine, d=0.24 (95% confidence interval [CI], −0.27 to 0.74); light monotherapy, 0.80 (95% CI, 0.28 to 1.31); and combination therapy, 1.11 (95% CI, 0.54 to 1.64). Effect sizes of more than 0.8 are often considered large.¹⁰

The treatment response (≥50% MADRS improvement) rate was highest in the combination treatment group (75.9%) with response rates to light monotherapy, placebo, and fluoxetine monotherapy of 50%, 33.3%, and 29%, respectively. There was a significant response effect for the combination vs placebo treatment group (P=.005). Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively) with a significant effect for the combination vs placebo treatment group (P=.02).

Combination therapy was superior to placebo in treatment response (≥50% reduction in the MADRS score) and remission (MADRS ≤10) with numbers needed to treat of 2.4 (95% CI, 1.6-5.8) and 3.5 (95% CI, 2.0-29.9), respectively.

By the end of the 8-week study period, 16 of 122 patients had dropped out; 2 reported lack of efficacy, 5 reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew consent.

What’s New? 

New evidence on a not-so-new treatment

We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious in increasing the remission rate of nonseasonal MDD.

Caveats 

Choice of SSRI, geography, and trial duration may have affected results

A single SSRI (fluoxetine) was used in this study; other more potent SSRIs might work better. This study was conducted in southern Canada, and light therapy may not demonstrate as large a benefit in regions located farther south. The study excluded pregnant and breastfeeding women.

The trial duration was relatively short, and the investigators did not attain their pre-planned sample size for the study, which limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

Also, it’s worth noting that there were trends for some adverse events (nausea, heartburn, weight gain, agitation, sexual dysfunction, and skin rash) to occur less frequently in the combination group than in the fluoxetine monotherapy group. Possible explanations are that the study had inadequate power, that the sham treatment did not adequately blind patients, or that light therapy can ameliorate some of the adverse effects of fluoxetine.

We now have evidence that bright light therapy, alone or in combination with fluoxetine, is efficacious in increasing the remission rate of nonseasonal major depressive disorder.

Challenges to Implementation

Commercial insurance doesn’t usually cover light therapy

Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹¹ Since only a few studies have tested light therapy for nonseasonal MDD, significant uncertainty remains about patient selection, as well as optimal dose, timing, and duration of light therapy in the management of nonseasonal MDD.¹² Although the risks associated with bright light therapy are minimal, the therapy can lead to mania or hypomania,³ so clinicians need to monitor for such effects when initiating therapy.

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which can be found in medical supply stores and online outlets, ranges between $118 and $237.^4,12 However, such devices are reusable, making the amortized cost almost negligible.¹³

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.