Susan London

MINNEAPOLIS – People with chronic insomnia don’t have to take the sedative-hypnotic agent zolpidem every night for it to remain efficacious, a randomized trial found.

Investigators enrolled in the trial 56 patients who had had a response to a priming phase of 4 weeks of nightly zolpidem (Ambien) 10 mg and assigned them to three maintenance strategies: nightly dosing, intermittent dosing (whereby the drug was taken 3-5 nights per week of the patient’s choice), and partial reinforcement dosing (whereby a capsule was taken every night, but half were placebos).

Use of partial reinforcement after a priming phase, during which the drug is repeatedly paired with sleep, taps into the phenomenon of conditioning, explained lead author Michael Perlis, Ph.D., director of the behavioral sleep medicine program, University of Pennsylvania, Philadelphia. "In this kind of paradigm, on the nights when there is no medication, they are getting a conditioned response; on the nights when there is medication, you are reinforcing the capsule as the conditioned stimulus for that physiologic response."

Analyses based on the 41 compliant patients showed that after 1 month, the three maintenance regimens were statistically indistinguishable in terms of measures such as time to relapse, sleep latency, and waking after sleep onset.

Total sleep time was longer with nightly dosing (463 minutes) and partial reinforcement dosing (459 minutes) than with intermittent dosing (429 minutes) (P = .002 across groups). Also, sleep efficiency was better with nightly dosing (90%) and partial reinforcement (91%) than with intermittent dosing (88%) (P = .002 across groups).

The frequency of medical symptoms, possibly adverse effects, was statistically indistinguishable across groups, although they tended to be least frequent with the partial reinforcement strategy and most with the intermittent dosing strategy.

"The present findings suggest that in compliant subjects, any of the three 10-mg strategies evaluated may be used to maintain treatment response over time. If a trend is evident, it’s that subjects in the intermittent dosing group condition do not do as well as nightly dosing and as in partial reinforcement, and that’s especially and significantly true for total sleep time and sleep efficiency," Dr. Perlis commented. "The take-home message is interspersing placebos between active doses appears to be a reasonable approach for maintaining clinical gains following priming, in other words, obtention of treatment response with a full-dose strategy."

In upcoming research, the investigators plan to see how low they can go with the partial reinforcement strategy as far as nights of zolpidem – even down to zero capsules of active drug – and still maintain the benefit of nightly dosing. If this proves successful, "then it may be possible to one, maintain treatment response for long periods of time with fractional amounts of medication. Second, we have a potential to reduce tolerance and side effect risks. Third, we would massively be able to reduce the cost of maintenance therapy considering placebos are basically free," he said.

"Finally and most important..., if this approach works as applied to insomnia, it may be a powerful tool for the management of medications with narrow therapeutic indices. Put differently, the partial reinforcement approach may be a strategy for managing medications that have nearly as much risk as they do benefit. That’s where the money is," said Dr. Perlis, who disclosed no relevant conflicts of interest.

In an interview, Brandy Roane, Ph.D., one of the session cochairs and a psychologist at the University of North Texas Health Science Center in Fort Worth, noted that the study is interesting in that it sheds light on why patients on intermittent dosing might become increasingly dependent on the medication.

"You have the patient who becomes more likely to increase their use even if it’s not effective, because they end up taking that dose on the night when they do sleep better because it would be a typical what we call crash night, where their body is already so physically fatigued and their homeostatic sleep pressure is so increased that they take it and it pairs it with that [sleep], and it’s a learned response: ‘I took medication and I slept so much better.’ Whereas if you hadn’t paired it with that, they would have slept better anyway," she explained.

"So I think it does look more at that real world type of setting and starts to speak to some of that possible use actually increasing the likelihood that they are going to take the medication, whether it’s effective or not, and then not use behavioral interventions that might be more effective."

Colin A. Espie, Ph.D., the other session cochair and a professor of sleep medicine in the Nuffield Department of Clinical Neuroscience at the University of Oxford (England), commented: "This is theoretically quite an interesting study. I think there might be some ethical problems in devising a practice whereby you systematically give people placebo without their knowledge, so I’m not sure it’s a very usable clinical strategy. But I think it’s an interesting paradigm to understand more about the placebo effect."

Dr. Perlis disclosed no relevant conflicts of interest.

MINNEAPOLIS – People with chronic insomnia don’t have to take the sedative-hypnotic agent zolpidem every night for it to remain efficacious, a randomized trial found.

Investigators enrolled in the trial 56 patients who had had a response to a priming phase of 4 weeks of nightly zolpidem (Ambien) 10 mg and assigned them to three maintenance strategies: nightly dosing, intermittent dosing (whereby the drug was taken 3-5 nights per week of the patient’s choice), and partial reinforcement dosing (whereby a capsule was taken every night, but half were placebos).

Use of partial reinforcement after a priming phase, during which the drug is repeatedly paired with sleep, taps into the phenomenon of conditioning, explained lead author Michael Perlis, Ph.D., director of the behavioral sleep medicine program, University of Pennsylvania, Philadelphia. "In this kind of paradigm, on the nights when there is no medication, they are getting a conditioned response; on the nights when there is medication, you are reinforcing the capsule as the conditioned stimulus for that physiologic response."

Analyses based on the 41 compliant patients showed that after 1 month, the three maintenance regimens were statistically indistinguishable in terms of measures such as time to relapse, sleep latency, and waking after sleep onset.

Total sleep time was longer with nightly dosing (463 minutes) and partial reinforcement dosing (459 minutes) than with intermittent dosing (429 minutes) (P = .002 across groups). Also, sleep efficiency was better with nightly dosing (90%) and partial reinforcement (91%) than with intermittent dosing (88%) (P = .002 across groups).

The frequency of medical symptoms, possibly adverse effects, was statistically indistinguishable across groups, although they tended to be least frequent with the partial reinforcement strategy and most with the intermittent dosing strategy.

"The present findings suggest that in compliant subjects, any of the three 10-mg strategies evaluated may be used to maintain treatment response over time. If a trend is evident, it’s that subjects in the intermittent dosing group condition do not do as well as nightly dosing and as in partial reinforcement, and that’s especially and significantly true for total sleep time and sleep efficiency," Dr. Perlis commented. "The take-home message is interspersing placebos between active doses appears to be a reasonable approach for maintaining clinical gains following priming, in other words, obtention of treatment response with a full-dose strategy."

In upcoming research, the investigators plan to see how low they can go with the partial reinforcement strategy as far as nights of zolpidem – even down to zero capsules of active drug – and still maintain the benefit of nightly dosing. If this proves successful, "then it may be possible to one, maintain treatment response for long periods of time with fractional amounts of medication. Second, we have a potential to reduce tolerance and side effect risks. Third, we would massively be able to reduce the cost of maintenance therapy considering placebos are basically free," he said.

"Finally and most important..., if this approach works as applied to insomnia, it may be a powerful tool for the management of medications with narrow therapeutic indices. Put differently, the partial reinforcement approach may be a strategy for managing medications that have nearly as much risk as they do benefit. That’s where the money is," said Dr. Perlis, who disclosed no relevant conflicts of interest.

In an interview, Brandy Roane, Ph.D., one of the session cochairs and a psychologist at the University of North Texas Health Science Center in Fort Worth, noted that the study is interesting in that it sheds light on why patients on intermittent dosing might become increasingly dependent on the medication.

"You have the patient who becomes more likely to increase their use even if it’s not effective, because they end up taking that dose on the night when they do sleep better because it would be a typical what we call crash night, where their body is already so physically fatigued and their homeostatic sleep pressure is so increased that they take it and it pairs it with that [sleep], and it’s a learned response: ‘I took medication and I slept so much better.’ Whereas if you hadn’t paired it with that, they would have slept better anyway," she explained.

"So I think it does look more at that real world type of setting and starts to speak to some of that possible use actually increasing the likelihood that they are going to take the medication, whether it’s effective or not, and then not use behavioral interventions that might be more effective."

Colin A. Espie, Ph.D., the other session cochair and a professor of sleep medicine in the Nuffield Department of Clinical Neuroscience at the University of Oxford (England), commented: "This is theoretically quite an interesting study. I think there might be some ethical problems in devising a practice whereby you systematically give people placebo without their knowledge, so I’m not sure it’s a very usable clinical strategy. But I think it’s an interesting paradigm to understand more about the placebo effect."

Dr. Perlis disclosed no relevant conflicts of interest.

MINNEAPOLIS – People with chronic insomnia don’t have to take the sedative-hypnotic agent zolpidem every night for it to remain efficacious, a randomized trial found.

Investigators enrolled in the trial 56 patients who had had a response to a priming phase of 4 weeks of nightly zolpidem (Ambien) 10 mg and assigned them to three maintenance strategies: nightly dosing, intermittent dosing (whereby the drug was taken 3-5 nights per week of the patient’s choice), and partial reinforcement dosing (whereby a capsule was taken every night, but half were placebos).

Use of partial reinforcement after a priming phase, during which the drug is repeatedly paired with sleep, taps into the phenomenon of conditioning, explained lead author Michael Perlis, Ph.D., director of the behavioral sleep medicine program, University of Pennsylvania, Philadelphia. "In this kind of paradigm, on the nights when there is no medication, they are getting a conditioned response; on the nights when there is medication, you are reinforcing the capsule as the conditioned stimulus for that physiologic response."

Analyses based on the 41 compliant patients showed that after 1 month, the three maintenance regimens were statistically indistinguishable in terms of measures such as time to relapse, sleep latency, and waking after sleep onset.

Total sleep time was longer with nightly dosing (463 minutes) and partial reinforcement dosing (459 minutes) than with intermittent dosing (429 minutes) (P = .002 across groups). Also, sleep efficiency was better with nightly dosing (90%) and partial reinforcement (91%) than with intermittent dosing (88%) (P = .002 across groups).

The frequency of medical symptoms, possibly adverse effects, was statistically indistinguishable across groups, although they tended to be least frequent with the partial reinforcement strategy and most with the intermittent dosing strategy.

"The present findings suggest that in compliant subjects, any of the three 10-mg strategies evaluated may be used to maintain treatment response over time. If a trend is evident, it’s that subjects in the intermittent dosing group condition do not do as well as nightly dosing and as in partial reinforcement, and that’s especially and significantly true for total sleep time and sleep efficiency," Dr. Perlis commented. "The take-home message is interspersing placebos between active doses appears to be a reasonable approach for maintaining clinical gains following priming, in other words, obtention of treatment response with a full-dose strategy."

In upcoming research, the investigators plan to see how low they can go with the partial reinforcement strategy as far as nights of zolpidem – even down to zero capsules of active drug – and still maintain the benefit of nightly dosing. If this proves successful, "then it may be possible to one, maintain treatment response for long periods of time with fractional amounts of medication. Second, we have a potential to reduce tolerance and side effect risks. Third, we would massively be able to reduce the cost of maintenance therapy considering placebos are basically free," he said.

"Finally and most important..., if this approach works as applied to insomnia, it may be a powerful tool for the management of medications with narrow therapeutic indices. Put differently, the partial reinforcement approach may be a strategy for managing medications that have nearly as much risk as they do benefit. That’s where the money is," said Dr. Perlis, who disclosed no relevant conflicts of interest.

In an interview, Brandy Roane, Ph.D., one of the session cochairs and a psychologist at the University of North Texas Health Science Center in Fort Worth, noted that the study is interesting in that it sheds light on why patients on intermittent dosing might become increasingly dependent on the medication.

"You have the patient who becomes more likely to increase their use even if it’s not effective, because they end up taking that dose on the night when they do sleep better because it would be a typical what we call crash night, where their body is already so physically fatigued and their homeostatic sleep pressure is so increased that they take it and it pairs it with that [sleep], and it’s a learned response: ‘I took medication and I slept so much better.’ Whereas if you hadn’t paired it with that, they would have slept better anyway," she explained.

"So I think it does look more at that real world type of setting and starts to speak to some of that possible use actually increasing the likelihood that they are going to take the medication, whether it’s effective or not, and then not use behavioral interventions that might be more effective."

Colin A. Espie, Ph.D., the other session cochair and a professor of sleep medicine in the Nuffield Department of Clinical Neuroscience at the University of Oxford (England), commented: "This is theoretically quite an interesting study. I think there might be some ethical problems in devising a practice whereby you systematically give people placebo without their knowledge, so I’m not sure it’s a very usable clinical strategy. But I think it’s an interesting paradigm to understand more about the placebo effect."

Dr. Perlis disclosed no relevant conflicts of interest.

MINNEAPOLIS – Continuous positive airway pressure works similarly well at lowering blood pressure in real-world clinical practice as in clinical trials, according to a cohort study of 880 patients with sleep-disordered breathing and hypertension.

The patients, 598 with hypertension that responded to therapy and 282 with idiopathic resistant hypertension, were all treated at a tertiary-care sleep disorders center between 2010 and 2013.

On average, a year after starting continuous positive airway pressure (CPAP), they had a reduction of 3.0 mm Hg in systolic blood pressure, 2.2 mm Hg in diastolic blood pressure, and 2.5 mm Hg in mean arterial pressure in analyses adjusted for potential confounders, researchers reported at the annual meeting of the Associated Professional Sleep Societies.

The benefit was similar regardless of whether hypertension was resistant or not, although patients with the resistant form had higher blood pressure – especially systolic blood pressure – at this time point.

"Our real-world experience is consistent with the blood pressure reduction seen with the use of CPAP in the rigorous clinical trials," commented lead researcher Dr. Harneet K. Walia, assistant professor of family medicine with the sleep disorders center at the Cleveland Clinic. "The clinic-based effectiveness data of CPAP on blood pressure in this pragmatic clinical study were similar in the resistant hypertension and non–resistant hypertension groups."

Study findings were essentially the same when neck size was substituted for body mass index as a potential confounder (although the multivariate model had a better fit) and when analyses were restricted to the 82% of patients who were adherent to CPAP, according to self-report.

In an interview, session cochair Dr. Cathy Anne Goldstein, assistant professor of neurology at the University of Michigan, Ann Arbor, said, "This is a promising study that does show the association of treating obstructive sleep apnea with CPAP and reducing blood pressure. This was nice because it showed it wasn’t just the patients who were refractory – it was all comers with hypertension who had a benefit."

"This isn’t new, but it’s confirmatory of what some other studies have shown," she added. "The more information we can get, the better, because there have been some conflicting results."

Dr. Walia disclosed no relevant conflicts of interest.

MINNEAPOLIS – Continuous positive airway pressure works similarly well at lowering blood pressure in real-world clinical practice as in clinical trials, according to a cohort study of 880 patients with sleep-disordered breathing and hypertension.

The patients, 598 with hypertension that responded to therapy and 282 with idiopathic resistant hypertension, were all treated at a tertiary-care sleep disorders center between 2010 and 2013.

On average, a year after starting continuous positive airway pressure (CPAP), they had a reduction of 3.0 mm Hg in systolic blood pressure, 2.2 mm Hg in diastolic blood pressure, and 2.5 mm Hg in mean arterial pressure in analyses adjusted for potential confounders, researchers reported at the annual meeting of the Associated Professional Sleep Societies.

The benefit was similar regardless of whether hypertension was resistant or not, although patients with the resistant form had higher blood pressure – especially systolic blood pressure – at this time point.

"Our real-world experience is consistent with the blood pressure reduction seen with the use of CPAP in the rigorous clinical trials," commented lead researcher Dr. Harneet K. Walia, assistant professor of family medicine with the sleep disorders center at the Cleveland Clinic. "The clinic-based effectiveness data of CPAP on blood pressure in this pragmatic clinical study were similar in the resistant hypertension and non–resistant hypertension groups."

Study findings were essentially the same when neck size was substituted for body mass index as a potential confounder (although the multivariate model had a better fit) and when analyses were restricted to the 82% of patients who were adherent to CPAP, according to self-report.

In an interview, session cochair Dr. Cathy Anne Goldstein, assistant professor of neurology at the University of Michigan, Ann Arbor, said, "This is a promising study that does show the association of treating obstructive sleep apnea with CPAP and reducing blood pressure. This was nice because it showed it wasn’t just the patients who were refractory – it was all comers with hypertension who had a benefit."

"This isn’t new, but it’s confirmatory of what some other studies have shown," she added. "The more information we can get, the better, because there have been some conflicting results."

Dr. Walia disclosed no relevant conflicts of interest.

MINNEAPOLIS – Continuous positive airway pressure works similarly well at lowering blood pressure in real-world clinical practice as in clinical trials, according to a cohort study of 880 patients with sleep-disordered breathing and hypertension.

The patients, 598 with hypertension that responded to therapy and 282 with idiopathic resistant hypertension, were all treated at a tertiary-care sleep disorders center between 2010 and 2013.

On average, a year after starting continuous positive airway pressure (CPAP), they had a reduction of 3.0 mm Hg in systolic blood pressure, 2.2 mm Hg in diastolic blood pressure, and 2.5 mm Hg in mean arterial pressure in analyses adjusted for potential confounders, researchers reported at the annual meeting of the Associated Professional Sleep Societies.

The benefit was similar regardless of whether hypertension was resistant or not, although patients with the resistant form had higher blood pressure – especially systolic blood pressure – at this time point.

"Our real-world experience is consistent with the blood pressure reduction seen with the use of CPAP in the rigorous clinical trials," commented lead researcher Dr. Harneet K. Walia, assistant professor of family medicine with the sleep disorders center at the Cleveland Clinic. "The clinic-based effectiveness data of CPAP on blood pressure in this pragmatic clinical study were similar in the resistant hypertension and non–resistant hypertension groups."

Study findings were essentially the same when neck size was substituted for body mass index as a potential confounder (although the multivariate model had a better fit) and when analyses were restricted to the 82% of patients who were adherent to CPAP, according to self-report.

In an interview, session cochair Dr. Cathy Anne Goldstein, assistant professor of neurology at the University of Michigan, Ann Arbor, said, "This is a promising study that does show the association of treating obstructive sleep apnea with CPAP and reducing blood pressure. This was nice because it showed it wasn’t just the patients who were refractory – it was all comers with hypertension who had a benefit."

"This isn’t new, but it’s confirmatory of what some other studies have shown," she added. "The more information we can get, the better, because there have been some conflicting results."

Dr. Walia disclosed no relevant conflicts of interest.

LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.

Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.

Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.

Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.

The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.

"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.

"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.

The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.

"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.

"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.

In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.

Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.

Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.

Dr. Batra disclosed no relevant conflicts of interest.

LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.

Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.

Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.

Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.

The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.

"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.

"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.

The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.

"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.

"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.

In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.

Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.

Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.

Dr. Batra disclosed no relevant conflicts of interest.

LAS VEGAS – Testosterone improves insulin sensitivity and insulin signaling in diabetic men who are deficient in this hormone, finds a randomized trial reported at the annual meeting of the American Association of Clinical Endocrinologists.

Investigators led by Dr. Manav Batra of the University at Buffalo, State University of New York, assigned 41 men with hypogonadotropic hypogonadism evenly to receive intramuscular testosterone (250 mg) or placebo every 2 weeks for 24 weeks. The testosterone dose was adjusted to achieve free testosterone levels in the mid-normal range for healthy young men.

Main results of the trial showed that men in the testosterone group had a statistically significant 32% improvement in insulin sensitivity from baseline, but their counterparts in the placebo group had essentially no change in this measure.

Testosterone treatment also was associated with increased expression in adipose tissue of genes that mediate insulin signaling and decreased expression in mononuclear cells of genes that mediate insulin resistance. Placebo treatment was not associated with any changes.

The findings are important, as roughly one-third of men with type 2 diabetes have hypogonadotropic hypogonadism and testosterone deficiency is linked to unfavorable metabolic, lipid, and anthropometric changes that may increase cardiovascular risk, according to Dr. Batra.

"Testosterone replacement reverses these changes, and there is decline in fat mass, increase in lean mass, decline in inflammatory markers, and improved insulin signaling and hence insulin sensitivity, which may potentially reduce cardiovascular risk," he said in an interview.

"As these changes may have a bearing on future cardiovascular outcomes in people with hypogonadotropic hypogonadism in type 2 diabetes, the results of this study will lay the foundations for future longer-term studies investigating the effects of testosterone replacement on atherosclerosis and cardiovascular disease in hypogonadal type 2 diabetic and obese subjects," he added.

The study is consistent with earlier research linking both low and high testosterone levels with insulin resistance, Dr. Edward S. Horton, comoderator of the session in which the data were reported, said in an interview.

"The idea that testosterone deficiency is associated with insulin resistance has been around for 30 years. I look at this study as basically showing by modern methods that some of these old ideas are really holding up – that that’s true," he said.

"The data are very interesting and good data showing that, for people who are hypogonadal, we should be treating them to improve insulin sensitivity and getting the beneficial effects of testosterone beyond just the androgenic effects," maintained Dr. Horton, director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, both in Boston.

In the study, the investigators first compared the 41 hypogonadal diabetic men participating in the trial with 50 eugonadal diabetic men, showing that the former did indeed have a host of adverse cardiometabolic measures when compared with the latter.

Among other favorable changes seen with testosterone treatment, men in that group had improvements from baseline in levels of insulin, homeostatic model assessment of insulin resistance (HOMA-IR), leptin, and C-reactive protein, Dr. Batra reported. Meanwhile, these measures remained unchanged in the placebo group.

Testosterone therapy was not associated with any significant improvements in levels of glucose or glycated hemoglobin, or in lipid profiles.

Dr. Batra disclosed no relevant conflicts of interest.

MINNEAPOLIS – Midlife insomnia increases the likelihood of retiring because of poor health or disability, a longitudinal cohort study among 1,590 Wisconsin state employees showed.

Previous research has established that insomniacs retire earlier than peers without this sleep disorder, according to lead researcher Lauren Hale, Ph.D., of the public health program, Stony Brook (N.Y.) University. But the reasons for retiring are unclear.

She and her colleagues analyzed data from the REST (Retirement and Sleep Trajectories Study) cohort, a mixed group of blue- and white-collar Wisconsin state employees who were followed from midlife onward and completed questionnaires probing their reasons for retiring.

Overall, 41% of the participants had insomnia at approximately 50 years of age based on their report of often or almost always experiencing at least one of four symptoms of the disorder, Dr. Hale reported at the annual meeting of the Associated Professional Sleep Societies.

As of 2013, two-thirds of the entire cohort had retired, most commonly citing reasons of wanting to do other things, being financially secure, and wanting more time to spend with family and friends.

But after the data were adjusted for covariates, insomnia was most strongly and significantly associated with retiring because of poor health or disability (P less than .001). And the more insomnia symptoms a participant reported, the higher his or her risk of retiring for this reason; those reporting three or four symptoms had approximately twice the risk of peers without insomnia.

Surprisingly, insomnia did not increase the risk of retirement because of being laid off (as might be expected if employees were frequently late to work because of sleep loss) or retirement because of needing to care for a family member (a stressor that might be expected to lead to insomnia), according to Dr. Hale.

"We confirmed our hypothesis that the leading reason that people who have insomnia symptoms in early life are retiring earlier is due to poor health or disability as they are getting older," she commented.

"Now, there is still work to be done; the temporal sequencing is not 100% clear," said Dr. Hale.

Although it appears that the insomnia is preceding poor health, which then triggers early retirement, it is also possible that the poor health comes first and gives rise to insomnia, ultimately leading to the decision to retire, she explained. And there is a third possibility. "There are of course many unmeasured health variables that we didn’t include in the models that might be preceding the insomnia at age 50 and then leading to early retirement. And of course there are a range of unmeasured factors – social, psychosocial, cultural – that could be leading to both concurrent insomnia and poor health, that lead to early retirement," she explained. "So we hope to probe into that in the future."

In an interview, session chair Dr. Nalaka S. Gooneratne of the department of medicine atthe Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Philadelphia, said: "I think these findings have very important public health ramifications. It’s very important for the field of sleep to not just look at the effects of sleep on immediate disease outcomes, but also on public health factors such as retirement and quality of life for retirees, and maximizing functional status and independence for older adults.

"Some of this data is really quite intriguing, suggesting there are hitherto unappreciated links between sleep and the decisions people make later on in their life about how they want to manage their retirement and finances," he added. "I think it’s very important to fund and explore research on the links between aging and sleep, especially with the growing numbers of older adults in the population."

Dr. Hale disclosed no relevant conflicts of interest.

MINNEAPOLIS – Midlife insomnia increases the likelihood of retiring because of poor health or disability, a longitudinal cohort study among 1,590 Wisconsin state employees showed.

Previous research has established that insomniacs retire earlier than peers without this sleep disorder, according to lead researcher Lauren Hale, Ph.D., of the public health program, Stony Brook (N.Y.) University. But the reasons for retiring are unclear.

She and her colleagues analyzed data from the REST (Retirement and Sleep Trajectories Study) cohort, a mixed group of blue- and white-collar Wisconsin state employees who were followed from midlife onward and completed questionnaires probing their reasons for retiring.

Overall, 41% of the participants had insomnia at approximately 50 years of age based on their report of often or almost always experiencing at least one of four symptoms of the disorder, Dr. Hale reported at the annual meeting of the Associated Professional Sleep Societies.

As of 2013, two-thirds of the entire cohort had retired, most commonly citing reasons of wanting to do other things, being financially secure, and wanting more time to spend with family and friends.

But after the data were adjusted for covariates, insomnia was most strongly and significantly associated with retiring because of poor health or disability (P less than .001). And the more insomnia symptoms a participant reported, the higher his or her risk of retiring for this reason; those reporting three or four symptoms had approximately twice the risk of peers without insomnia.

Surprisingly, insomnia did not increase the risk of retirement because of being laid off (as might be expected if employees were frequently late to work because of sleep loss) or retirement because of needing to care for a family member (a stressor that might be expected to lead to insomnia), according to Dr. Hale.

"We confirmed our hypothesis that the leading reason that people who have insomnia symptoms in early life are retiring earlier is due to poor health or disability as they are getting older," she commented.

"Now, there is still work to be done; the temporal sequencing is not 100% clear," said Dr. Hale.

Although it appears that the insomnia is preceding poor health, which then triggers early retirement, it is also possible that the poor health comes first and gives rise to insomnia, ultimately leading to the decision to retire, she explained. And there is a third possibility. "There are of course many unmeasured health variables that we didn’t include in the models that might be preceding the insomnia at age 50 and then leading to early retirement. And of course there are a range of unmeasured factors – social, psychosocial, cultural – that could be leading to both concurrent insomnia and poor health, that lead to early retirement," she explained. "So we hope to probe into that in the future."

In an interview, session chair Dr. Nalaka S. Gooneratne of the department of medicine atthe Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Philadelphia, said: "I think these findings have very important public health ramifications. It’s very important for the field of sleep to not just look at the effects of sleep on immediate disease outcomes, but also on public health factors such as retirement and quality of life for retirees, and maximizing functional status and independence for older adults.

"Some of this data is really quite intriguing, suggesting there are hitherto unappreciated links between sleep and the decisions people make later on in their life about how they want to manage their retirement and finances," he added. "I think it’s very important to fund and explore research on the links between aging and sleep, especially with the growing numbers of older adults in the population."

Dr. Hale disclosed no relevant conflicts of interest.

MINNEAPOLIS – Midlife insomnia increases the likelihood of retiring because of poor health or disability, a longitudinal cohort study among 1,590 Wisconsin state employees showed.

Previous research has established that insomniacs retire earlier than peers without this sleep disorder, according to lead researcher Lauren Hale, Ph.D., of the public health program, Stony Brook (N.Y.) University. But the reasons for retiring are unclear.

She and her colleagues analyzed data from the REST (Retirement and Sleep Trajectories Study) cohort, a mixed group of blue- and white-collar Wisconsin state employees who were followed from midlife onward and completed questionnaires probing their reasons for retiring.

Overall, 41% of the participants had insomnia at approximately 50 years of age based on their report of often or almost always experiencing at least one of four symptoms of the disorder, Dr. Hale reported at the annual meeting of the Associated Professional Sleep Societies.

As of 2013, two-thirds of the entire cohort had retired, most commonly citing reasons of wanting to do other things, being financially secure, and wanting more time to spend with family and friends.

But after the data were adjusted for covariates, insomnia was most strongly and significantly associated with retiring because of poor health or disability (P less than .001). And the more insomnia symptoms a participant reported, the higher his or her risk of retiring for this reason; those reporting three or four symptoms had approximately twice the risk of peers without insomnia.

Surprisingly, insomnia did not increase the risk of retirement because of being laid off (as might be expected if employees were frequently late to work because of sleep loss) or retirement because of needing to care for a family member (a stressor that might be expected to lead to insomnia), according to Dr. Hale.

"We confirmed our hypothesis that the leading reason that people who have insomnia symptoms in early life are retiring earlier is due to poor health or disability as they are getting older," she commented.

"Now, there is still work to be done; the temporal sequencing is not 100% clear," said Dr. Hale.

Although it appears that the insomnia is preceding poor health, which then triggers early retirement, it is also possible that the poor health comes first and gives rise to insomnia, ultimately leading to the decision to retire, she explained. And there is a third possibility. "There are of course many unmeasured health variables that we didn’t include in the models that might be preceding the insomnia at age 50 and then leading to early retirement. And of course there are a range of unmeasured factors – social, psychosocial, cultural – that could be leading to both concurrent insomnia and poor health, that lead to early retirement," she explained. "So we hope to probe into that in the future."

In an interview, session chair Dr. Nalaka S. Gooneratne of the department of medicine atthe Hospital of the University of Pennsylvania and the Presbyterian Medical Center of Philadelphia, said: "I think these findings have very important public health ramifications. It’s very important for the field of sleep to not just look at the effects of sleep on immediate disease outcomes, but also on public health factors such as retirement and quality of life for retirees, and maximizing functional status and independence for older adults.

"Some of this data is really quite intriguing, suggesting there are hitherto unappreciated links between sleep and the decisions people make later on in their life about how they want to manage their retirement and finances," he added. "I think it’s very important to fund and explore research on the links between aging and sleep, especially with the growing numbers of older adults in the population."

Dr. Hale disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, finds a cohort study reported at the annual meeting of the Associated Professional Sleep Societies.

Researchers studied 98 asymptomatic, cognitively healthy late-middle-age adults from the WRAP (Wisconsin Registry for Alzheimer’s Prevention) program, the majority of whom were at elevated risk for the disease because of family history.

Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease (P less than .05).

"It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young in terms of amyloid pathology," commented first author Kate Sprecher, a PhD candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk.

"In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep," she added. "Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early."

The investigators plan to further investigate the observed association using objective measures of sleep and obstructive sleep apnea (OSA), according to Ms. Sprecher. "And we’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease," she said.

Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by positron emission tomography performed with Pittsburgh Compound B.

The participants were 63 years old, on average, and two-thirds were female, reported Ms. Sprecher, who disclosed no conflicts of interest relevant to the research. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele, which is associated with risk of this disease.

Analyses adjusted for these and other potential confounders showed a correlation (P less than or equal to .05) between somnolence on the MOS Sleep Scale – the average of scores for drowsiness, trouble staying awake, and napping – and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).

Poorer quality of sleep was correlated (P less than or equal to .05) with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25).

Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas.

Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.

"This could be because the two questionnaires probe slightly different aspects of sleepiness," Ms. Sprecher proposed in an interview. "The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day."

Ms. Sprecher disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.

In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.

"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.

Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."

In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."

The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."

In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.

After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.

In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.

However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.

Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.

The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.

Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.

Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.

In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.

"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.

Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."

In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."

The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."

In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.

After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.

In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.

However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.

Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.

The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.

Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.

Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.

MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.

In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.

"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.

Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."

In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."

The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."

In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.

After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.

In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.

However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.

Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.

The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.

Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.

Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.

MINNEAPOLIS – Both cognitive behavioral therapy for insomnia and mindfulness-based stress reduction training lessened insomnia in a group of cancer survivors, although the former works faster, new data show.

Investigators compared the two therapies head to head in I-CAN SLEEP (A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer), a randomized, partially blinded noninferiority trial among 111 adult patients from a tertiary care center in Calgary, Alta., who had nonmetastatic cancer and were at least 1 month out from completion of treatment. The behavioral therapies lasted 8 weeks.

At the end of the behavioral therapy, mindfulness-based stress reduction (MBSR) was inferior to cognitive behavioral therapy for insomnia (CBT-I) in terms of the difference in Insomnia Severity Index. But at 3 months, MBSR met the noninferiority criterion, with the 3.47-point upper bound of the confidence interval for the difference between groups falling within the predefined 4-point threshold (P = .01), Sheila N. Garland, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies. The data were recently published (J. Clin. Oncol. 2014;32:449-57).

Also at 3 months, diary data showed that sleep-onset latency had fallen from baseline by 14 minutes with MBSR and 22 minutes with CBT-I. The groups had a similar reduction in wake after sleep onset of about 35 minutes. Total sleep time increased by 0.73 hours with MBSR and 0.60 hours with CBT-I. Sleep efficiency improved by approximately 8% and 12%. And both therapies achieved a significant reduction in stress and mood disturbance.

"We confirmed that CBT-I produces faster effects and durable effects [when compared with] MBSR, but at 3 months, the two treatments are somewhat comparable and MBSR was not inferior according to our definition," said Dr. Garland of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

"Both treatments were demonstrated to be effective for reducing symptoms of stress and mood disturbance, but I do believe that longer-term follow-up and comparisons are necessary because where CBT-I might be easy to grasp within, say, a 4-week period, mindfulness-based techniques are going to maybe take a little bit longer to incorporate into someone’s life and maybe apply to their sleep. So perhaps more practice is needed before we actually see longer effects."

Importantly, the rate of loss to follow-up at 3 months was 15% with CBT-I but a dramatic 50% with MBSR, with most of this dropout occurring within the first three sessions, noted Dr. Garland. She attributed the latter to the fact that patients were not aware of the specific treatments that were being compared when they agreed to participate in the study, which might have prevented dropout if they did not receive their preferred treatment.

"I actually believe that the blinding may underestimate clinical effectiveness, and this is because these people wouldn’t have normally chosen to practice mindfulness meditation, and that’s an important thing to note in terms of delivering behavioral interventions: people have to be willing, they have to buy into the intervention. So that’s what I think actually contributed to the large dropout," she elaborated. "You would see probably better improvement if they actually chose to go to that intervention. So my intention to blind participants to prevent that preferential dropout ... Well, these results say they are going to drop out anyway.

"This suggests that we should not apply a ‘one-size-fits-all model’ to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences," she added in an interview.

Session cochair Colin Espie, Ph.D., D.Sc., a professor of sleep medicine in the Nuffield department of clinical neuroscience at the University of Oxford (England), commented, "I think it’s really good to see other treatments being used, particularly in comorbid populations because clearly for people with cancer, sleep is occurring in a particular context and there may be advantages of a mindful approach to your situation in general, of which sleep is a part."

"But I thought there were maybe some design flaws there in that [the patients] maybe didn’t get what they thought was [being offered]. So maybe they thought they’d be getting treatment for insomnia, and it might not be obvious to people that mindfulness was focused on that," he added in an interview.

Dr. Espie also expressed reservations about the small sample size. "I think that to do a noninferiority trial, you need very, very large numbers because you really need to be able to demonstrate that you’ve properly tested the hypothesis and found no difference between those groups. And it was probably quite underpowered from that point of view," he said.

Dr. Garland disclosed no relevant conflicts of interest.

MINNEAPOLIS – Both cognitive behavioral therapy for insomnia and mindfulness-based stress reduction training lessened insomnia in a group of cancer survivors, although the former works faster, new data show.

Investigators compared the two therapies head to head in I-CAN SLEEP (A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer), a randomized, partially blinded noninferiority trial among 111 adult patients from a tertiary care center in Calgary, Alta., who had nonmetastatic cancer and were at least 1 month out from completion of treatment. The behavioral therapies lasted 8 weeks.

At the end of the behavioral therapy, mindfulness-based stress reduction (MBSR) was inferior to cognitive behavioral therapy for insomnia (CBT-I) in terms of the difference in Insomnia Severity Index. But at 3 months, MBSR met the noninferiority criterion, with the 3.47-point upper bound of the confidence interval for the difference between groups falling within the predefined 4-point threshold (P = .01), Sheila N. Garland, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies. The data were recently published (J. Clin. Oncol. 2014;32:449-57).

Also at 3 months, diary data showed that sleep-onset latency had fallen from baseline by 14 minutes with MBSR and 22 minutes with CBT-I. The groups had a similar reduction in wake after sleep onset of about 35 minutes. Total sleep time increased by 0.73 hours with MBSR and 0.60 hours with CBT-I. Sleep efficiency improved by approximately 8% and 12%. And both therapies achieved a significant reduction in stress and mood disturbance.

"We confirmed that CBT-I produces faster effects and durable effects [when compared with] MBSR, but at 3 months, the two treatments are somewhat comparable and MBSR was not inferior according to our definition," said Dr. Garland of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

"Both treatments were demonstrated to be effective for reducing symptoms of stress and mood disturbance, but I do believe that longer-term follow-up and comparisons are necessary because where CBT-I might be easy to grasp within, say, a 4-week period, mindfulness-based techniques are going to maybe take a little bit longer to incorporate into someone’s life and maybe apply to their sleep. So perhaps more practice is needed before we actually see longer effects."

Importantly, the rate of loss to follow-up at 3 months was 15% with CBT-I but a dramatic 50% with MBSR, with most of this dropout occurring within the first three sessions, noted Dr. Garland. She attributed the latter to the fact that patients were not aware of the specific treatments that were being compared when they agreed to participate in the study, which might have prevented dropout if they did not receive their preferred treatment.

"I actually believe that the blinding may underestimate clinical effectiveness, and this is because these people wouldn’t have normally chosen to practice mindfulness meditation, and that’s an important thing to note in terms of delivering behavioral interventions: people have to be willing, they have to buy into the intervention. So that’s what I think actually contributed to the large dropout," she elaborated. "You would see probably better improvement if they actually chose to go to that intervention. So my intention to blind participants to prevent that preferential dropout ... Well, these results say they are going to drop out anyway.

"This suggests that we should not apply a ‘one-size-fits-all model’ to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences," she added in an interview.

Session cochair Colin Espie, Ph.D., D.Sc., a professor of sleep medicine in the Nuffield department of clinical neuroscience at the University of Oxford (England), commented, "I think it’s really good to see other treatments being used, particularly in comorbid populations because clearly for people with cancer, sleep is occurring in a particular context and there may be advantages of a mindful approach to your situation in general, of which sleep is a part."

"But I thought there were maybe some design flaws there in that [the patients] maybe didn’t get what they thought was [being offered]. So maybe they thought they’d be getting treatment for insomnia, and it might not be obvious to people that mindfulness was focused on that," he added in an interview.

Dr. Espie also expressed reservations about the small sample size. "I think that to do a noninferiority trial, you need very, very large numbers because you really need to be able to demonstrate that you’ve properly tested the hypothesis and found no difference between those groups. And it was probably quite underpowered from that point of view," he said.

Dr. Garland disclosed no relevant conflicts of interest.

MINNEAPOLIS – Both cognitive behavioral therapy for insomnia and mindfulness-based stress reduction training lessened insomnia in a group of cancer survivors, although the former works faster, new data show.

Investigators compared the two therapies head to head in I-CAN SLEEP (A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer), a randomized, partially blinded noninferiority trial among 111 adult patients from a tertiary care center in Calgary, Alta., who had nonmetastatic cancer and were at least 1 month out from completion of treatment. The behavioral therapies lasted 8 weeks.

At the end of the behavioral therapy, mindfulness-based stress reduction (MBSR) was inferior to cognitive behavioral therapy for insomnia (CBT-I) in terms of the difference in Insomnia Severity Index. But at 3 months, MBSR met the noninferiority criterion, with the 3.47-point upper bound of the confidence interval for the difference between groups falling within the predefined 4-point threshold (P = .01), Sheila N. Garland, Ph.D., reported at the annual meeting of the Associated Professional Sleep Societies. The data were recently published (J. Clin. Oncol. 2014;32:449-57).

Also at 3 months, diary data showed that sleep-onset latency had fallen from baseline by 14 minutes with MBSR and 22 minutes with CBT-I. The groups had a similar reduction in wake after sleep onset of about 35 minutes. Total sleep time increased by 0.73 hours with MBSR and 0.60 hours with CBT-I. Sleep efficiency improved by approximately 8% and 12%. And both therapies achieved a significant reduction in stress and mood disturbance.

"We confirmed that CBT-I produces faster effects and durable effects [when compared with] MBSR, but at 3 months, the two treatments are somewhat comparable and MBSR was not inferior according to our definition," said Dr. Garland of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

"Both treatments were demonstrated to be effective for reducing symptoms of stress and mood disturbance, but I do believe that longer-term follow-up and comparisons are necessary because where CBT-I might be easy to grasp within, say, a 4-week period, mindfulness-based techniques are going to maybe take a little bit longer to incorporate into someone’s life and maybe apply to their sleep. So perhaps more practice is needed before we actually see longer effects."

Importantly, the rate of loss to follow-up at 3 months was 15% with CBT-I but a dramatic 50% with MBSR, with most of this dropout occurring within the first three sessions, noted Dr. Garland. She attributed the latter to the fact that patients were not aware of the specific treatments that were being compared when they agreed to participate in the study, which might have prevented dropout if they did not receive their preferred treatment.

"I actually believe that the blinding may underestimate clinical effectiveness, and this is because these people wouldn’t have normally chosen to practice mindfulness meditation, and that’s an important thing to note in terms of delivering behavioral interventions: people have to be willing, they have to buy into the intervention. So that’s what I think actually contributed to the large dropout," she elaborated. "You would see probably better improvement if they actually chose to go to that intervention. So my intention to blind participants to prevent that preferential dropout ... Well, these results say they are going to drop out anyway.

"This suggests that we should not apply a ‘one-size-fits-all model’ to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences," she added in an interview.

Session cochair Colin Espie, Ph.D., D.Sc., a professor of sleep medicine in the Nuffield department of clinical neuroscience at the University of Oxford (England), commented, "I think it’s really good to see other treatments being used, particularly in comorbid populations because clearly for people with cancer, sleep is occurring in a particular context and there may be advantages of a mindful approach to your situation in general, of which sleep is a part."

"But I thought there were maybe some design flaws there in that [the patients] maybe didn’t get what they thought was [being offered]. So maybe they thought they’d be getting treatment for insomnia, and it might not be obvious to people that mindfulness was focused on that," he added in an interview.

Dr. Espie also expressed reservations about the small sample size. "I think that to do a noninferiority trial, you need very, very large numbers because you really need to be able to demonstrate that you’ve properly tested the hypothesis and found no difference between those groups. And it was probably quite underpowered from that point of view," he said.

Dr. Garland disclosed no relevant conflicts of interest.

MINNEAPOLIS – Cognitive behavioral therapy tailored for insomnia management and delivered by health educators eased sleep impairment in older adults in a randomized trial of 159 community-dwelling veterans aged 60 years or older with chronic insomnia.

Researchers assigned the veterans to individual cognitive behavioral therapy for insomnia (CBT-I), group CBT-I, or general sleep education and hygiene as a control. The CBT-I combined sleep restriction, stimulus control, and cognitive therapy and was provided by health educators – primarily masters-level professionals – who had weekly telephone access to behavioral sleep medicine specialists. All study groups had five sessions of their assigned treatment over 6 weeks.

CBT-I was associated with better self-reported sleep quality and reduced insomnia symptoms compared with controls 6 months after therapy, according to data presented at the annual meeting of the Associated Professional Sleep Societies. And it worked similarly well whether provided one-on-one or in groups.

"We believe future work is needed to disseminate and implement this and other innovative models of CBT-I ... So it’s very important that there is continued, ongoing work to fine-tune the CBT-I interventions," but particularly in older adults, in whom the risks of episodic or chronic use of sleeping pills may be particularly problematic, said Dr. Cathy A. Alessi, a geriatrician with the VA Greater Los Angeles Healthcare System in North Hills, Calif., and professor of medicine at the David Geffen School of Medicine at UCLA. "We feel strongly that it’s time to get these out into routine practice."

Some parts of the country have few or no sleep medicine specialists, she noted. Thus, the ability to use allied health professionals to deliver this safe and effective treatment should make it available to more patients.

Session cochair Brandy Roane, Ph.D., of the University of North Texas Health Science Center at Fort Worth, noted that the study is helpful in that it provides insight on the feasibility and efficacy of CBT-I in this patient population.

"As our population is aging and we are trying to use more behavioral-based interventions, it is important for us to look at the efficacy. Are they even going to engage in the intervention? Are they going to get lost in it?" asked Dr. Roane.

Do they have age-related inability to understand some of the concepts and do the required cognitive work? And if they are cognitively impaired, will CBT-I be effective? she asked. "Also, are they going to be able to change their behavior in general?"

Importantly, Dr. Roane noted, in addition to its sleep benefits, CBT-I could have a general health and cognitive benefit during the daytime.

The mean age of the veterans in the study was 72 years. They were cognitively healthy, and had no or only mild sleep apnea. But on average, they had six other health conditions in addition to insomnia.

At 6 months, the trial’s primary endpoint, the Pittsburgh Sleep Quality Index score was 7.7 for the control condition, but lower at 5.8 for individual CBT-I (P = .005) and 5.6 for group CBT-I (P = .002). Relative to the control condition, both CBT-I strategies yielded significantly better sleep-onset latency, total wake time, and sleep efficiency as assessed from sleep diaries. Differences in these measures were still significant at 12 months.

The groups were statistically indistinguishable, however, with respect to changes in sleep efficiency as assessed from wrist actigraphy, depressive symptoms, and health-related quality of life.

In related qualitative research, also presented at the meeting (Josephson et al., abstract 0544), the investigators conducted focus groups among the study veterans to get their impressions of the CBT-I model of care, Dr. Alessi noted in an interview.

"Many participants we spoke with preferred behavioral treatment for insomnia over sleeping medications, and were also very receptive to the idea of behavioral treatment being provided by health educators [and others] outside of the mental health setting [as was the case in our study]," she reported. "We also heard compelling anecdotes from participants who described dramatic improvements in their sleep problems, which, for many, had been present for years."

Dr. Alessi disclosed no relevant conflicts of interest.

MINNEAPOLIS – Cognitive behavioral therapy tailored for insomnia management and delivered by health educators eased sleep impairment in older adults in a randomized trial of 159 community-dwelling veterans aged 60 years or older with chronic insomnia.

Researchers assigned the veterans to individual cognitive behavioral therapy for insomnia (CBT-I), group CBT-I, or general sleep education and hygiene as a control. The CBT-I combined sleep restriction, stimulus control, and cognitive therapy and was provided by health educators – primarily masters-level professionals – who had weekly telephone access to behavioral sleep medicine specialists. All study groups had five sessions of their assigned treatment over 6 weeks.

CBT-I was associated with better self-reported sleep quality and reduced insomnia symptoms compared with controls 6 months after therapy, according to data presented at the annual meeting of the Associated Professional Sleep Societies. And it worked similarly well whether provided one-on-one or in groups.

"We believe future work is needed to disseminate and implement this and other innovative models of CBT-I ... So it’s very important that there is continued, ongoing work to fine-tune the CBT-I interventions," but particularly in older adults, in whom the risks of episodic or chronic use of sleeping pills may be particularly problematic, said Dr. Cathy A. Alessi, a geriatrician with the VA Greater Los Angeles Healthcare System in North Hills, Calif., and professor of medicine at the David Geffen School of Medicine at UCLA. "We feel strongly that it’s time to get these out into routine practice."

Some parts of the country have few or no sleep medicine specialists, she noted. Thus, the ability to use allied health professionals to deliver this safe and effective treatment should make it available to more patients.

Session cochair Brandy Roane, Ph.D., of the University of North Texas Health Science Center at Fort Worth, noted that the study is helpful in that it provides insight on the feasibility and efficacy of CBT-I in this patient population.

"As our population is aging and we are trying to use more behavioral-based interventions, it is important for us to look at the efficacy. Are they even going to engage in the intervention? Are they going to get lost in it?" asked Dr. Roane.

Do they have age-related inability to understand some of the concepts and do the required cognitive work? And if they are cognitively impaired, will CBT-I be effective? she asked. "Also, are they going to be able to change their behavior in general?"

Importantly, Dr. Roane noted, in addition to its sleep benefits, CBT-I could have a general health and cognitive benefit during the daytime.

The mean age of the veterans in the study was 72 years. They were cognitively healthy, and had no or only mild sleep apnea. But on average, they had six other health conditions in addition to insomnia.

At 6 months, the trial’s primary endpoint, the Pittsburgh Sleep Quality Index score was 7.7 for the control condition, but lower at 5.8 for individual CBT-I (P = .005) and 5.6 for group CBT-I (P = .002). Relative to the control condition, both CBT-I strategies yielded significantly better sleep-onset latency, total wake time, and sleep efficiency as assessed from sleep diaries. Differences in these measures were still significant at 12 months.

The groups were statistically indistinguishable, however, with respect to changes in sleep efficiency as assessed from wrist actigraphy, depressive symptoms, and health-related quality of life.

In related qualitative research, also presented at the meeting (Josephson et al., abstract 0544), the investigators conducted focus groups among the study veterans to get their impressions of the CBT-I model of care, Dr. Alessi noted in an interview.

"Many participants we spoke with preferred behavioral treatment for insomnia over sleeping medications, and were also very receptive to the idea of behavioral treatment being provided by health educators [and others] outside of the mental health setting [as was the case in our study]," she reported. "We also heard compelling anecdotes from participants who described dramatic improvements in their sleep problems, which, for many, had been present for years."

Dr. Alessi disclosed no relevant conflicts of interest.

MINNEAPOLIS – Cognitive behavioral therapy tailored for insomnia management and delivered by health educators eased sleep impairment in older adults in a randomized trial of 159 community-dwelling veterans aged 60 years or older with chronic insomnia.

Researchers assigned the veterans to individual cognitive behavioral therapy for insomnia (CBT-I), group CBT-I, or general sleep education and hygiene as a control. The CBT-I combined sleep restriction, stimulus control, and cognitive therapy and was provided by health educators – primarily masters-level professionals – who had weekly telephone access to behavioral sleep medicine specialists. All study groups had five sessions of their assigned treatment over 6 weeks.

CBT-I was associated with better self-reported sleep quality and reduced insomnia symptoms compared with controls 6 months after therapy, according to data presented at the annual meeting of the Associated Professional Sleep Societies. And it worked similarly well whether provided one-on-one or in groups.

"We believe future work is needed to disseminate and implement this and other innovative models of CBT-I ... So it’s very important that there is continued, ongoing work to fine-tune the CBT-I interventions," but particularly in older adults, in whom the risks of episodic or chronic use of sleeping pills may be particularly problematic, said Dr. Cathy A. Alessi, a geriatrician with the VA Greater Los Angeles Healthcare System in North Hills, Calif., and professor of medicine at the David Geffen School of Medicine at UCLA. "We feel strongly that it’s time to get these out into routine practice."

Some parts of the country have few or no sleep medicine specialists, she noted. Thus, the ability to use allied health professionals to deliver this safe and effective treatment should make it available to more patients.

Session cochair Brandy Roane, Ph.D., of the University of North Texas Health Science Center at Fort Worth, noted that the study is helpful in that it provides insight on the feasibility and efficacy of CBT-I in this patient population.

"As our population is aging and we are trying to use more behavioral-based interventions, it is important for us to look at the efficacy. Are they even going to engage in the intervention? Are they going to get lost in it?" asked Dr. Roane.

Do they have age-related inability to understand some of the concepts and do the required cognitive work? And if they are cognitively impaired, will CBT-I be effective? she asked. "Also, are they going to be able to change their behavior in general?"

Importantly, Dr. Roane noted, in addition to its sleep benefits, CBT-I could have a general health and cognitive benefit during the daytime.

The mean age of the veterans in the study was 72 years. They were cognitively healthy, and had no or only mild sleep apnea. But on average, they had six other health conditions in addition to insomnia.

At 6 months, the trial’s primary endpoint, the Pittsburgh Sleep Quality Index score was 7.7 for the control condition, but lower at 5.8 for individual CBT-I (P = .005) and 5.6 for group CBT-I (P = .002). Relative to the control condition, both CBT-I strategies yielded significantly better sleep-onset latency, total wake time, and sleep efficiency as assessed from sleep diaries. Differences in these measures were still significant at 12 months.

The groups were statistically indistinguishable, however, with respect to changes in sleep efficiency as assessed from wrist actigraphy, depressive symptoms, and health-related quality of life.

In related qualitative research, also presented at the meeting (Josephson et al., abstract 0544), the investigators conducted focus groups among the study veterans to get their impressions of the CBT-I model of care, Dr. Alessi noted in an interview.

"Many participants we spoke with preferred behavioral treatment for insomnia over sleeping medications, and were also very receptive to the idea of behavioral treatment being provided by health educators [and others] outside of the mental health setting [as was the case in our study]," she reported. "We also heard compelling anecdotes from participants who described dramatic improvements in their sleep problems, which, for many, had been present for years."

Dr. Alessi disclosed no relevant conflicts of interest.

MINNEAPOLIS – After 12 weeks of treatment with a novel agent, narcolepsy patients showed an 86% improvement from baseline in scores on the Clinical Global Impression-Change scale, compared with 38% of placebo patients. The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

JZP-110 (formerly ADX-N05), a wake-promoting agent with dopaminergic and noradrenergic activity, reduced symptoms in a phase IIb randomized, double-blind, placebo-controlled trial of 93 patients with narcolepsy, according to Dr. Jed Black of the Stanford (Calif.) Center for Sleep Sciences and Medicine in Redwood City, and a part-time employee of Jazz Pharmaceuticals in Palo Alto.

"This is a wake-promoting agent with a mechanism of action that is somewhat distinct from those that are currently available for treating excessive daytime sleepiness in narcolepsy, with what appears to be a robust and fairly consistent effect across studies to improve alertness ... and also to impact narcolepsy globally," he said.

At week 4, the average change in sleep-onset latency on the Maintenance of Wakefulness Test (MWT) was 9.5 minutes in the active drug group and 1.4 minutes in the placebo group (P less than .0001). The proportion of treatment patients vs. placebo patients with improved Clinical Global Impression – Change scale (CGI-C) scores was 80% vs. 51%, respectively (P = .0066), and Epworth Sleepiness Scale (ESS) scores decreased in the two groups by 5.6 points vs. 2.4 points, respectively (P = .0038).

Additional improvements were noted at 12 weeks, with an average change in sleep-onset latency on the MWT of 12.8 minutes vs. 2.1 minutes (P less than .0001), likely representing a dose response instead of a time-on-treatment response, Dr. Black said.

The researchers randomized 49 patients to placebo and 44 to the active drug. The active drug was initiated at 150 mg/day for 4 weeks, and increased to 300 mg/day for weeks 5-12.

The two primary efficacy endpoints were improvements from baseline in average sleep-onset latency on the MWT and improvements from baseline on the CGI-C; change on the ESS was a secondary endpoint.

The drug might fill an unmet need in narcolepsy patients who do not improve on or cannot tolerate existing treatment options for excessive sleepiness, Dr. Black noted. Additionally, it is not associated with rebound hypersomnia, and limited preclinical data suggest that it may have lower potential for abuse than traditional stimulants, he said.

The study "was exciting in that it presented expanded research on a new wake-promoting compound which likely works differently than currently available wake-promoting agents," session chair Dr. Douglas Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston, said in an interview.

ESS scores fell by 8.5 points in the treatment group vs. 2.5 points in the placebo group (P less than .0001) – putting all of the patients in the active drug group within the normal range

Prolongation of sleep-onset latency with the drug was not affected by whether patients had cataplexy (about a third of cases), said Dr. Black.

Adverse events were more common in the treatment group, and included headache, insomnia, diarrhea, nausea, decreased appetite, anxiety, and irritability. "There was sort of a dose-response on the GI symptoms and...insomnia and also anxiety and irritability," he noted.

Three patients discontinued the drug because of adverse events, compared with two who stopped placebo. Two serious events – acute cholecystitis and conversion disorder (the latter in a patient who had previously experienced this disorder) – occurred in the treatment group, but were deemed unrelated to the drug.

The study was supported by Aerial BioPharma. Dr. Black is a part-time employee of Jazz Pharmaceuticals, which has licensed ADX-N05 from Aerial BioPharma, and other study authors reported associations with the company.

MINNEAPOLIS – After 12 weeks of treatment with a novel agent, narcolepsy patients showed an 86% improvement from baseline in scores on the Clinical Global Impression-Change scale, compared with 38% of placebo patients. The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

JZP-110 (formerly ADX-N05), a wake-promoting agent with dopaminergic and noradrenergic activity, reduced symptoms in a phase IIb randomized, double-blind, placebo-controlled trial of 93 patients with narcolepsy, according to Dr. Jed Black of the Stanford (Calif.) Center for Sleep Sciences and Medicine in Redwood City, and a part-time employee of Jazz Pharmaceuticals in Palo Alto.

"This is a wake-promoting agent with a mechanism of action that is somewhat distinct from those that are currently available for treating excessive daytime sleepiness in narcolepsy, with what appears to be a robust and fairly consistent effect across studies to improve alertness ... and also to impact narcolepsy globally," he said.

At week 4, the average change in sleep-onset latency on the Maintenance of Wakefulness Test (MWT) was 9.5 minutes in the active drug group and 1.4 minutes in the placebo group (P less than .0001). The proportion of treatment patients vs. placebo patients with improved Clinical Global Impression – Change scale (CGI-C) scores was 80% vs. 51%, respectively (P = .0066), and Epworth Sleepiness Scale (ESS) scores decreased in the two groups by 5.6 points vs. 2.4 points, respectively (P = .0038).

Additional improvements were noted at 12 weeks, with an average change in sleep-onset latency on the MWT of 12.8 minutes vs. 2.1 minutes (P less than .0001), likely representing a dose response instead of a time-on-treatment response, Dr. Black said.

The researchers randomized 49 patients to placebo and 44 to the active drug. The active drug was initiated at 150 mg/day for 4 weeks, and increased to 300 mg/day for weeks 5-12.

The two primary efficacy endpoints were improvements from baseline in average sleep-onset latency on the MWT and improvements from baseline on the CGI-C; change on the ESS was a secondary endpoint.

The drug might fill an unmet need in narcolepsy patients who do not improve on or cannot tolerate existing treatment options for excessive sleepiness, Dr. Black noted. Additionally, it is not associated with rebound hypersomnia, and limited preclinical data suggest that it may have lower potential for abuse than traditional stimulants, he said.

The study "was exciting in that it presented expanded research on a new wake-promoting compound which likely works differently than currently available wake-promoting agents," session chair Dr. Douglas Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston, said in an interview.

ESS scores fell by 8.5 points in the treatment group vs. 2.5 points in the placebo group (P less than .0001) – putting all of the patients in the active drug group within the normal range

Prolongation of sleep-onset latency with the drug was not affected by whether patients had cataplexy (about a third of cases), said Dr. Black.

Adverse events were more common in the treatment group, and included headache, insomnia, diarrhea, nausea, decreased appetite, anxiety, and irritability. "There was sort of a dose-response on the GI symptoms and...insomnia and also anxiety and irritability," he noted.

Three patients discontinued the drug because of adverse events, compared with two who stopped placebo. Two serious events – acute cholecystitis and conversion disorder (the latter in a patient who had previously experienced this disorder) – occurred in the treatment group, but were deemed unrelated to the drug.

The study was supported by Aerial BioPharma. Dr. Black is a part-time employee of Jazz Pharmaceuticals, which has licensed ADX-N05 from Aerial BioPharma, and other study authors reported associations with the company.

MINNEAPOLIS – After 12 weeks of treatment with a novel agent, narcolepsy patients showed an 86% improvement from baseline in scores on the Clinical Global Impression-Change scale, compared with 38% of placebo patients. The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

JZP-110 (formerly ADX-N05), a wake-promoting agent with dopaminergic and noradrenergic activity, reduced symptoms in a phase IIb randomized, double-blind, placebo-controlled trial of 93 patients with narcolepsy, according to Dr. Jed Black of the Stanford (Calif.) Center for Sleep Sciences and Medicine in Redwood City, and a part-time employee of Jazz Pharmaceuticals in Palo Alto.

"This is a wake-promoting agent with a mechanism of action that is somewhat distinct from those that are currently available for treating excessive daytime sleepiness in narcolepsy, with what appears to be a robust and fairly consistent effect across studies to improve alertness ... and also to impact narcolepsy globally," he said.

At week 4, the average change in sleep-onset latency on the Maintenance of Wakefulness Test (MWT) was 9.5 minutes in the active drug group and 1.4 minutes in the placebo group (P less than .0001). The proportion of treatment patients vs. placebo patients with improved Clinical Global Impression – Change scale (CGI-C) scores was 80% vs. 51%, respectively (P = .0066), and Epworth Sleepiness Scale (ESS) scores decreased in the two groups by 5.6 points vs. 2.4 points, respectively (P = .0038).

Additional improvements were noted at 12 weeks, with an average change in sleep-onset latency on the MWT of 12.8 minutes vs. 2.1 minutes (P less than .0001), likely representing a dose response instead of a time-on-treatment response, Dr. Black said.

The researchers randomized 49 patients to placebo and 44 to the active drug. The active drug was initiated at 150 mg/day for 4 weeks, and increased to 300 mg/day for weeks 5-12.

The two primary efficacy endpoints were improvements from baseline in average sleep-onset latency on the MWT and improvements from baseline on the CGI-C; change on the ESS was a secondary endpoint.

The drug might fill an unmet need in narcolepsy patients who do not improve on or cannot tolerate existing treatment options for excessive sleepiness, Dr. Black noted. Additionally, it is not associated with rebound hypersomnia, and limited preclinical data suggest that it may have lower potential for abuse than traditional stimulants, he said.

The study "was exciting in that it presented expanded research on a new wake-promoting compound which likely works differently than currently available wake-promoting agents," session chair Dr. Douglas Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston, said in an interview.

ESS scores fell by 8.5 points in the treatment group vs. 2.5 points in the placebo group (P less than .0001) – putting all of the patients in the active drug group within the normal range

Prolongation of sleep-onset latency with the drug was not affected by whether patients had cataplexy (about a third of cases), said Dr. Black.

Adverse events were more common in the treatment group, and included headache, insomnia, diarrhea, nausea, decreased appetite, anxiety, and irritability. "There was sort of a dose-response on the GI symptoms and...insomnia and also anxiety and irritability," he noted.

Three patients discontinued the drug because of adverse events, compared with two who stopped placebo. Two serious events – acute cholecystitis and conversion disorder (the latter in a patient who had previously experienced this disorder) – occurred in the treatment group, but were deemed unrelated to the drug.

The study was supported by Aerial BioPharma. Dr. Black is a part-time employee of Jazz Pharmaceuticals, which has licensed ADX-N05 from Aerial BioPharma, and other study authors reported associations with the company.

MINNEAPOLIS – People with seasonal affective disorder (SAD) have reduced retinal sensitivity to light all year long, suggests a study reported at the annual meeting of the Associated Professional Sleep Societies. And such lower sensitivity predicts the night-owl behavioral pattern that is one feature of this disorder.

Individuals with SAD, compared with healthy controls, have impaired cellular responses in a specific neural pathway, Kathryn A. Roecklein, Ph.D., of the University of Pittsburgh, said in an interview. "This neural pathway starts in the retina," with ganglion cells containing the protein melanopsin, "and goes to the central circadian clock in the brain and allows our bodies to synchronize with the environmental light/dark cycle."

"Surprisingly, melanopsin cell responses were lower in SAD year-round, in summer and winter, compared with controls. This means that impaired melanopsin cell responses are likely to make individuals vulnerable to SAD when light levels are lower on dark, winter days," she added.

In the study, the investigators measured the sensitivity of melanopsin cells to light with the postillumination pupil response (PIPR) test, and they plan to assess whether this test predicts treatment response, according to Dr. Roecklein.

"We are hoping that the PIPR test, which is similar to going to the ophthalmologist, will offer patients and their doctors a quick and easy way to choose from the multiple treatment options for depression: light therapy, antidepressant medication, and psychotherapy," she explained. Such prediction "could improve treatment fidelity, motivation to engage in treatment, and response rates."

The study "was an interesting look at the possible underpinnings of SAD, based on testing on the physiological responses from light coming into the eye," session chair Dr. Douglas B. Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston commented in an interview.

"This novel research may eventually help identify people at risk for SAD and, looking forward, may phenotype the SAD patients most likely to respond to different treatments such as light or antidepressant medication," he agreed.

Previous research has shown that relative to unaffected peers, people with SAD have a reduced melanopsin cell response in winter (Psychiatry Res. 2013;210:150-158), but it is unclear whether this is a season-specific phenomenon.

In their study, the investigators measured postillumination pupil response during summer and winter in 33 individuals with SAD and 17 healthy individuals, using 1-second light exposures to red light and to blue light for testing.

Relative to healthy peers, individuals with SAD had a smaller postillumination pupil response year-round (P = .004). But in addition, going from summer to winter, the response decreased in the SAD group whereas it increased in the healthy group, suggesting that SAD is also due to failure of a normal upregulation that kicks in as light dwindles later in the year, according to Dr. Roecklein.

Additional results showed that individuals with a smaller postillumination pupil response were more likely to be night owls vs. early risers (P less than .00001).

After adjusting for age and sex, the SAD group had more of a night-owl pattern than did the healthy group year round (P less than .001), although within the former group, this pattern was somewhat more pronounced in the winter.

The study was funded by a grant from the National Institutes of Health and supported by the University of Pittsburgh Sleep Medicine Institute, and the Center for the Neural Basis of Cognition, a joint venture between the University of Pittsburgh and Carnegie Mellon University. The authors reported having no financial disclosures.

MINNEAPOLIS – People with seasonal affective disorder (SAD) have reduced retinal sensitivity to light all year long, suggests a study reported at the annual meeting of the Associated Professional Sleep Societies. And such lower sensitivity predicts the night-owl behavioral pattern that is one feature of this disorder.

Individuals with SAD, compared with healthy controls, have impaired cellular responses in a specific neural pathway, Kathryn A. Roecklein, Ph.D., of the University of Pittsburgh, said in an interview. "This neural pathway starts in the retina," with ganglion cells containing the protein melanopsin, "and goes to the central circadian clock in the brain and allows our bodies to synchronize with the environmental light/dark cycle."

"Surprisingly, melanopsin cell responses were lower in SAD year-round, in summer and winter, compared with controls. This means that impaired melanopsin cell responses are likely to make individuals vulnerable to SAD when light levels are lower on dark, winter days," she added.

In the study, the investigators measured the sensitivity of melanopsin cells to light with the postillumination pupil response (PIPR) test, and they plan to assess whether this test predicts treatment response, according to Dr. Roecklein.

"We are hoping that the PIPR test, which is similar to going to the ophthalmologist, will offer patients and their doctors a quick and easy way to choose from the multiple treatment options for depression: light therapy, antidepressant medication, and psychotherapy," she explained. Such prediction "could improve treatment fidelity, motivation to engage in treatment, and response rates."

The study "was an interesting look at the possible underpinnings of SAD, based on testing on the physiological responses from light coming into the eye," session chair Dr. Douglas B. Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston commented in an interview.

"This novel research may eventually help identify people at risk for SAD and, looking forward, may phenotype the SAD patients most likely to respond to different treatments such as light or antidepressant medication," he agreed.

Previous research has shown that relative to unaffected peers, people with SAD have a reduced melanopsin cell response in winter (Psychiatry Res. 2013;210:150-158), but it is unclear whether this is a season-specific phenomenon.

In their study, the investigators measured postillumination pupil response during summer and winter in 33 individuals with SAD and 17 healthy individuals, using 1-second light exposures to red light and to blue light for testing.

Relative to healthy peers, individuals with SAD had a smaller postillumination pupil response year-round (P = .004). But in addition, going from summer to winter, the response decreased in the SAD group whereas it increased in the healthy group, suggesting that SAD is also due to failure of a normal upregulation that kicks in as light dwindles later in the year, according to Dr. Roecklein.

Additional results showed that individuals with a smaller postillumination pupil response were more likely to be night owls vs. early risers (P less than .00001).

After adjusting for age and sex, the SAD group had more of a night-owl pattern than did the healthy group year round (P less than .001), although within the former group, this pattern was somewhat more pronounced in the winter.

The study was funded by a grant from the National Institutes of Health and supported by the University of Pittsburgh Sleep Medicine Institute, and the Center for the Neural Basis of Cognition, a joint venture between the University of Pittsburgh and Carnegie Mellon University. The authors reported having no financial disclosures.

MINNEAPOLIS – People with seasonal affective disorder (SAD) have reduced retinal sensitivity to light all year long, suggests a study reported at the annual meeting of the Associated Professional Sleep Societies. And such lower sensitivity predicts the night-owl behavioral pattern that is one feature of this disorder.

Individuals with SAD, compared with healthy controls, have impaired cellular responses in a specific neural pathway, Kathryn A. Roecklein, Ph.D., of the University of Pittsburgh, said in an interview. "This neural pathway starts in the retina," with ganglion cells containing the protein melanopsin, "and goes to the central circadian clock in the brain and allows our bodies to synchronize with the environmental light/dark cycle."

"Surprisingly, melanopsin cell responses were lower in SAD year-round, in summer and winter, compared with controls. This means that impaired melanopsin cell responses are likely to make individuals vulnerable to SAD when light levels are lower on dark, winter days," she added.

In the study, the investigators measured the sensitivity of melanopsin cells to light with the postillumination pupil response (PIPR) test, and they plan to assess whether this test predicts treatment response, according to Dr. Roecklein.

"We are hoping that the PIPR test, which is similar to going to the ophthalmologist, will offer patients and their doctors a quick and easy way to choose from the multiple treatment options for depression: light therapy, antidepressant medication, and psychotherapy," she explained. Such prediction "could improve treatment fidelity, motivation to engage in treatment, and response rates."

The study "was an interesting look at the possible underpinnings of SAD, based on testing on the physiological responses from light coming into the eye," session chair Dr. Douglas B. Kirsch of the Sleep Disorders Service at the Brigham & Women’s Hospital in Boston commented in an interview.

"This novel research may eventually help identify people at risk for SAD and, looking forward, may phenotype the SAD patients most likely to respond to different treatments such as light or antidepressant medication," he agreed.

Previous research has shown that relative to unaffected peers, people with SAD have a reduced melanopsin cell response in winter (Psychiatry Res. 2013;210:150-158), but it is unclear whether this is a season-specific phenomenon.

In their study, the investigators measured postillumination pupil response during summer and winter in 33 individuals with SAD and 17 healthy individuals, using 1-second light exposures to red light and to blue light for testing.

Relative to healthy peers, individuals with SAD had a smaller postillumination pupil response year-round (P = .004). But in addition, going from summer to winter, the response decreased in the SAD group whereas it increased in the healthy group, suggesting that SAD is also due to failure of a normal upregulation that kicks in as light dwindles later in the year, according to Dr. Roecklein.

Additional results showed that individuals with a smaller postillumination pupil response were more likely to be night owls vs. early risers (P less than .00001).

After adjusting for age and sex, the SAD group had more of a night-owl pattern than did the healthy group year round (P less than .001), although within the former group, this pattern was somewhat more pronounced in the winter.

The study was funded by a grant from the National Institutes of Health and supported by the University of Pittsburgh Sleep Medicine Institute, and the Center for the Neural Basis of Cognition, a joint venture between the University of Pittsburgh and Carnegie Mellon University. The authors reported having no financial disclosures.