Chris Aiken, MD

The average patient with bipolar disorder (BD) spends half their life struggling with mood symptoms and the other half struggling with sleep.

 Insomnia persists in 70% of patients even when their mood is stable, and these sleep problems put them at risk for more episodes of mania and depression (

 Some clinicians are liberal with hypnotics, while others prefer the lower abuse potential of sedating antidepressants like trazodone. Both these approaches have problems. Fortunately, there are also new therapies that improve mood and sleep by entraining the circadian rhythm (

 or z-hypnotic (eg, eszopiclone, zaleplon, zolpidem) could halt the progression of insomnia into mania, but the idea has never been adequately tested. These GABAergic hypnotics lack controlled trials in BD, and the few observational studies paint a mixed picture. A chart review of 278 z-hypnotic trials in adolescents with BD concluded that the drugs improved 

 in 40% to 60% of patients and did not lead to abuse with long-term use.

 On the other hand, reports document 30 cases of high doses of zolpidem and regular doses of alprazolam and triazolam inducing mania.

In contrast, clonazepam and lorazepam appear safer, with small controlled trials suggesting that these agents do not worsen, and may improve, manic symptoms (the 

 were not used as hypnotics in these trials).

 However, over the long term, benzodiazepines carry risks of tolerance and dependence, and long-term use may worsen cognition and mood in BD, according to nonrandomized studies that attempted to control for the confounding tendency to prescribe benzodiazepines in more severe cases.

 in BD is to choose mood stabilizers with sedative effects. Many antipsychotics are sedating, but some have more meaningful benefits in sleep quality; these include quetiapine in particular, and possibly lumateperone, olanzapine, 

Lithium is rarely sedating, but it does have positive effects on the circadian system, such as dampening the phase-advance (“night owl”) tendency that is associated with poorer health and greater risk of depression.

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Daniel C. McFarland, DO; Luigi Grassi, MD; Michelle Riba, MD, MS, DFAPA, FAPM

Helping Patients With Attentional Difficulties and Maladaptive Use of Psychoactive Substances

Sedating antidepressants are more problematic, particularly in bipolar I disorder, in which the risk of manic induction is high. Most, including trazodone and 

, are associated with case reports of triggering mania. In a retrospective study, patients with BD who used sedating antidepressants for sleep were significantly more likely to develop mania and episode acceleration than those who took traditional hypnotics.

Melatonin agonists have captured the interest of investigators because of their potential to realign the circadian system, which is often disrupted in BD. Pure melatonin failed to improve sleep, 

, or rapid cycling in 2 small controlled trials,

 but the melatonin agonist ramelteon has intriguing results from 3 industry-sponsored, randomized, placebo-controlled trials in BD. Although ramelteon failed to improve sleep or mania, it did prevent depression in patients who struggled with insomnia.

The first study tested ramelteon in 21 patients with acute mania and found a reduction in depressive symptoms but no benefit in mania or sleep.

 Next, ramelteon was tested in 83 patients with BD who had active 

 but stable mood. For 6 months, they took either placebo or a nightly dose of ramelteon 8 mg. As in the first trial, ramelteon did little to improve sleep (there was only a nonsignificant trend), but it did lower the risk of depression, more than doubling the time to a new episode from 84 to 188 days (P = .02).

 A larger study attempted to replicate that finding, but the results were negative across all outcomes.

One explanation for these intriguing results is that the positive trials enrolled patients with active insomnia, while the negative trial did not, suggesting that ramelteon might have preferential effects in patients with disturbed circadian rhythms. But then why didn’t the drug improve their sleep? These studies relied on subjective measures of sleep, and ramelteon has a poor track record on subjective outcomes. In primary insomnia, it improved subjective sleep onset by only 4 minutes over placebo and objective sleep onset by 9 minutes. 

 showed the reverse pattern, improving subjective onset by 14 minutes but objective onset by only 4 minutes (placebo, by the way, is no dud, and improved sleep onset by 8 to 20 minutes).

One thing to take away from this is the importance of setting realistic expectations when starting patients on ramelteon. This hypnotic is not like the others: It is relatively nonsedating and has no anxiolytic, amnestic, or rewarding effects. On the one hand, those qualities improve on its safety, but they are unlikely to endear it to patients with BD, who often want a hypnotic to quiet the anxious, racing thoughts that rev up as they try to fall asleep. Ramelteon will do none of that, but nor will it cause patients to fall, overuse their medication, or engage in complex sleep behaviors like cooking or driving in the middle of the night. One positive aspect that most patients appreciate is the lack of tolerance and withdrawal with ramelteon. Rather than wearing off, ramelteon’s sleep benefits built up over weeks to months in some studies.

While ramelteon is a melatonin agonist, dark therapy is a behavioral treatment that enhances endogenous melatonin by keeping patients in a pitch-dark room overnight. Dark therapy was developed by Thomas Wehr, MD, who speculated that evening darkness might improve sleep and mania in the same way that morning light improves 

 and circadian rhythms. In the 1990s, he recruited normal participants with mild sleep problems to the National Institute of Mental Health, where they stayed in a pitch-dark room overnight from 6:00 pm to 8:00 am. After a few weeks of this dark therapy, their sleep improved.

 Next, he turned his attention to BD, and found that the same protocol stabilized refractory rapid cycling.

Further studies supported Wehr’s observation, but it was not until the discovery of blue light–blocking glasses that dark therapy became practical for everyday use. In theory, the physiologic changes associated with total darkness might be achieved by 

, because the receptor that regulates melatonin secretion—melanopsin—responds only to the blue spectrum. The hope in that theory is that patients might be able to practice dark therapy while still being able to see in the evening.

Psychiatrist James Phelps, MD, first tested that hope in private practice, and his results were later confirmed in a randomized, placebo-controlled trial in Norway. For the entire evening from 6:00 pm to 8:00 am, patients hospitalized with acute mania wore blue light–blocking glasses or, if sleeping or trying to sleep, stayed in a pitch-dark room without the glasses. Within a week, their 

 improved with a large effect size (1.86) compared with a placebo group that wore gray glasses.

The dark therapy protocol can be gradually relaxed after recovery, allowing patients to put the glasses on a few hours before bed to prevent future episodes. That relaxed protocol also improves the sleep, according to 3 randomized controlled trials in primary insomnia. Wearing blue light–blockers 1.5 to 3 hours before bed helped patients fall asleep earlier and stay asleep longer, and improved sleep quality as well as mood and 

 However, blue light blockers do not have a strong sedative effect. In line with their circadian mechanism, they improve the regularity of sleep more than they improve subjective measures of insomnia.

A critical step in dark therapy is finding glasses that filter close to 100% of blue light. Lenses that were tested in clinical trials include Uvex Skyper S1933X, Uvex Ultra-spec 2000 ($10 to $15) and, for more comfort at a higher price, glasses at lowbluelights.com ($50). More information on the nuts and bolts of dark therapy is available in the Psych Pearls podcasts from August and October 2021.

Cognitive behavioral therapy for insomnia (CBT-i) is thought to work by stabilizing the circadian system, making it a natural fit for mood disorders. In unipolar depression, CBT-i improves mood and sleep, but the therapy is often avoided in BD because it requires patients to limit their time in bed, raising concerns that this sleep deprivation could trigger mania. In 2015, Allison Harvey, PhD, and colleagues at the University of California – Berkeley modified the CBT-i protocol to include a built-in safety valve for BD (CBT-iBD). The newer therapy limits bed restriction to no fewer than 6.5 hours.

CBT-iBD also includes techniques to address common circadian rhythm abnormalities in BD, such sleep inertia (a prolonged sense of grogginess in the morning) and nocturnal hyperactivity. To counter these sleep-disrupting tendencies, patients develop a wake-up routine encompassing bright light and energizing activity, and an evening wind-down routine in which the lights are dimmed and 

To test the therapy, Harvey recruited 58 patients with stable BD but active insomnia and randomized them to CBT-iBD or a psychoeducational therapy. At the end of the 8-week therapy, patients in the CBT-iBD group were sleeping better compared with controls, but more profound changes came later. After 6 months, those who learned CBT-iBD had an 8-fold reduction in mood problems, spending an average of 3.3 days in a mood episode vs 25.5 days for controls.

Later, Bryony Sheaves, DClinPsy, BSc, CPsychol, and colleagues adapted CBT-iBD for patients with schizophrenia, major depression, and BD in an inpatient crisis unit. The 2-week program improved sleep and well-being, and it hastened discharge by 8.5 days compared to treatment as usual.

It can be difficult to find therapists who practice CBT-insomnia, but the core program is available through a prescription app (Somryst) or a free, VA-sponsored app (CBT-i Coach). These programs can be adjusted for BD with the modifications described above.

Dark therapy and CBT-i are safe in the young and old, and a few tips can help adapt these treatments for different ages. Adolescents often have severe night-owl tendencies, which can be corrected by having the patient wake up 15 to 30 minutes earlier each day and wearing blue light–blockers in the early evening (eg, 5:00 pm to 8:00 pm). Napping is common in older adults but is discouraged in the CBT-i protocol. One compromise is to have the patient eliminate naps during the therapy, and then gradually add them back in once regular sleep is restored. Then they can continue the naps as long as they do not cause a relapse into insomnia. Finally, for patients of all ages who are afraid of the dark, there are nightlights that emit zero blue light (at lowbluelights.com and Amazon).

Although no hypnotics are FDA approved in children and adolescents, lithium and several antipsychotics (eg, quetiapine) are approved for them. In the elderly, the risks of falls and cognitive impairment have placed most hypnotics on the “inappropriate” list of the Beers criteria, although ramelteon is well studied in older adults and approved by the Beers.

Treating insomnia in BD is both an art and a science, requiring practitioners to balance the patient’s goal of rapid sedation with the more therapeutic approach of retraining the circadian rhythm. Circadian therapies like ramelteon, dark therapy, and CBT-insomnia have a slow build, but they promise more lasting and substantial benefits for mood and sleep than fast-acting hypnotics.

is the Mood Disorders Section Editor for 

, Editor in Chief of The Carlat Psychiatry Report, and director of the Mood Treatment Center. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for The Depression and Bipolar Workbook and from W.W. Norton & Co for

 Bipolar, Not So Much: Understanding Your Mood Swings and Depression.

1. Judd LL, Schettler PJ, Akiskal HS, et al. 

Long-term symptomatic status of bipolar I vs bipolar II disorders.

2. Harvey AG, Soehner AM, Kaplan KA, et al

. Treating insomnia improves mood state, sleep, and functioning in bipolar disorder: a pilot randomized controlled trial.

3. Schaffer CB, Schaffer LC, Miller AR, et al. 

Efficacy and safety of nonbenzodiazepine hypnotics for chronic insomnia in patients with bipolar disorder.

4. Sabe M, Kashef H, Gironi C, Sentissi O. 

Zolpidem stimulant effect: induced mania case report and systematic review of cases.

Prog Neuropsychopharmacol Biol Psychiatry.

A case of alprazolam, but not lorazepam, inducing manic symptoms.

6. Singh J, Skrzypcak B, Yasaei R, Mangat N. 

Triazolam-induced mania in a patient with bipolar I disorder following a dental procedure.

Clonazepam and lorazepam in acute mania: a Bayesian meta-analysis.

8. Cañada Y, Sabater A, Sierra P, et al. 

The effect of concomitant benzodiazepine use on neurocognition in stable, long-term patients with bipolar disorder.

9. Perlis RH, Ostacher MJ, Miklowitz DJ, et al. 

Benzodiazepine use and risk of recurrence in bipolar disorder: a STEP-BD report.

The effect of second-generation antipsychotic drugs on sleep parameters in patients with unipolar or bipolar disorder

11. Xu N, Shinohara K, Saunders KEA, et al. 

Effect of lithium on circadian rhythm in bipolar disorder: a systematic review and meta-analysis.

12. Saiz-Ruiz J, Cebollada A, Ibañez A. 

Sleep disorders in bipolar depression: hypnotics vs sedative antidepressants.

13. Quested DJ, Gibson JC, Sharpley AL, et al. 

Melatonin in acute mania investigation (MIAMI-UK). A randomized controlled trial of add-on melatonin in bipolar disorder.

14. McElroy SL, Winstanley EL, Martens B, et al. 

A randomized, placebo-controlled study of adjunctive ramelteon in ambulatory bipolar I disorder with manic symptoms and sleep disturbance.

15. Norris ER, Burke K, Correll JR, et al. 

A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder.

16. Mahableshwarkar AR, Calabrese JR, Macek TA, et al. 

Efficacy and safety of sublingual ramelteon as an adjunctive therapy in the maintenance treatment of bipolar I disorder in adults: a phase 3, randomized controlled trial.

A review of ramelteon in the treatment of sleep disorders.

19. Barbato G, Barker C, Bender C, et al. 

Extended sleep in humans in 14 hour nights (LD 10:14): relationship between REM density and spontaneous awakening.

20. Wehr TA, Turner EH, Shimada JM, et al. 

Treatment of rapidly cycling bipolar patient by using extended bed rest and darkness to stabilize the timing and duration of sleep.

21. Henriksen TE, Skrede S, Fasmer OB, et al. 

Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial.

Amber lenses to block blue light and improve sleep: a randomized trial.

23. Shechter A, Kim EW, St-Onge MP, Westwood AJ. 

Blocking nocturnal blue light for insomnia: a randomized controlled trial.

24. Zimmerman ME, Kim MB, Hale C, et al. 

Neuropsychological function response to nocturnal blue light blockage in individuals with symptoms of insomnia: a pilot randomized controlled study.

25. Aiken C, Newsome K. Blue light blockers: a behavior therapy for mania. 

. October 7, 2021. Accessed December 23, 2021. 

https://www.psychiatrictimes.com/view/blue-light-blockers-behavior-therapy-for-mania

26. Janků K, Šmotek M, Fárková E, Kopřivová J. 

Block the light and sleep well: evening blue light filtration as a part of cognitive behavioral therapy for insomnia

Interventions for sleep disturbance in bipolar disorder.

Articles

The average patient with bipolar disorder struggles with sleep disorders. Here's how you can help. 

New Directions for Insomnia and Bipolar Disorder

Stimulant medications have long been the mainstay of treatment for attention-deficit/hyperactivity disorder, but psychopharmacology is no longer the only game in town. Join us for a discussion on new nonpharmacological treatment approaches as Dr Chris Aiken, Psychiatric TimesTM Mood Disorders Section Editor and the Director of the Mood Treatment Center, talks with Dr Stephen Faraone, Distinguished Professor and Vice Chair of Research of Psychiatry and Behavioral Sciences at Upstate Medical University.

Podcasts

Upcoming Podcast on ADHD Treatment Options

Three Myths About Bipolar Disorder

Slideshows

Don't fall into the trap of these 3 myths about mania in bipolar disorder...

Last month we taught you how evening light can worsen mood. Today we teach you how to fix that. 

, "the voice of psychiatry." With thoughtful insights into the world of mental health, this podcast provides timely clinical commentary and practical cutting-edge pearls for you and your practice. We hope you enjoy.

I’m Chris Aiken, the Mood Disorders Section Editor for 

, and I’m Kellie Newsome, a psychiatric NP and the cohost of the 

: Evening light worsens sleep and mood, and 

 we unraveled the biology behind that association. To recap, evening light – particularly the blue wavelength suppresses melatonin, worsening 2 systems that are already fragile in people with mood disorders: sleep and circadian rhythms. In animal studies it even altered the core architecture of the brain – shrinking the dendritic spines that 

But you don’t have to go into the woods and live deliberately to fix this problem. Today, we’ll teach you how to use blue light filters to stabilize the circadian rhythms that regulate mood and sleep, and how to use them in 

: There are 2 well-known photoreceptors in the eye. The rods see black and white, and the cones add color vision. But in the 1990s a new photoreceptor was discovered – melanopsin – which only responds to the blue wavelength of light. This photoreceptor doesn’t help us see, but it does regulate our circadian rhythm. In the past, this system worked well because we didn’t have much blue light in the evening. There were candles, starlight, fireplaces – all yellow light.

: Except once a month when the blue moon was full. And it’s no coincidence the word lunatic arose in the middle ages as a term for mental illness. It was believed that some people went into temporary bouts of insanity that followed the lunar cycle – the moon. Seven hundred years later, 

 linking the full moon to worsening of psychiatric disorders continue to roll in.

: And in today’s world, every night is a full moon, because cell phones, plasma TVs, and energy efficient bulbs emit a lot of blue light. But technology has also come to the rescue in the form of blue light filtering glasses. These are amber colored glasses, and when you wear them they filter out close to 100% of blue light. They’ve gained popularity among sports figures and celebrities, because wearing them at night improves sleep – which then raises cognitive and athletic performance. But most models out there do not filter enough blue light to make a meaningful difference in psychiatric disorders. We recommend the glasses that were used in the clinical research – and there are 2 types. Some studies have used Uvex glasses, eg Uvex Skyper S1933X and Uvex Ultra-spec 2000, which are $10 to 15 dollars on Amazon.

Any pair on that site will work, and these are much better quality for a higher price, around $50.

: I keep a pair of these glasses at my desk for patients to try on. They’re usually surprised to see the world looks quite pleasant through them. They don’t make things dark, but give the world a relaxing, yellow hue. Some patients find them so soothing that I have to warn patients not to wear them during the day, because doing so will flip their circadian rhythm in the wrong direction. When you wear them, your brain will think it’s in pitch darkness, and we only want that effect at night.

: Wearing them has real biological effects. When you put them on, your melatonin starts to rise, the same as it does in a 

 Sometimes patients ask if they can just take melatonin instead, but that doesn’t have the same effect. In a recent randomized controlled trial, taking artificial melatonin did nothing to stabilize mood in bipolar disorder.

 So it’s not enough to have melatonin drizzled on the brain. There are other biological effects involved in pumping out the brain’s indigenous melatonin that are necessary here.

If you want to know more about the biological effects of light and darkness listen to our August 2nd podcast on 

Blue Light, Depression, and Bipolar Disorder

. Now, let’s move on to the clinical research.

: In the 1980s Thomas Wehr, MD, and Norman Rosenthal, MD, made a surprise discovery while working at the National Institute of Mental Health (NIMH). Some patients had worsened depression in the wintertime that improved with light therapy. Their research suggested that circadian rhythms played a strong role in mood disorders, something that was already hinted at by the high rates of insomnia in major depression and the fact that a night without sleep often triggered an episode of mania. So, Wehr turned his attention from morning light to evening darkness. He began with normal subjects and placed them in a pitch-dark room for 14 hours overnight, imitating a dark winter night where the sun goes down at 6 PM and rises at 8 AM. The subjects were a little sleep deprived before the experiment, getting about 7 hours per night, something Wehr thought might be due to the artificial evening light of modern life. After a few weeks in the dark bedroom, their 

 to 8 hours and 15 minutes per night, closer to the recommended amount an adult needs.

: Then in 1994 a man came to the NIMH seeking help for rapid cycling bipolar disorder. Most patients don’t call up the NIMH to get help, so we can imagine this man had a pretty bad case. He was a successful engineer with a hyperthymic temperament, but in his 40s he became depressed and started fluoxetine and nortriptyline. He got better on this combination, but then went into a 4-year bout of rapid cycling moods cycling in and out of depression and hypomania every 1 to 2 months. Mood stabilizers did not help, so he came to the NIMH. Wehr knew that sleep disruption could trigger rapid cycling, and he wondered if his super-dark room could stabilize it. He put the patient through the same protocol he used for sleep, placing him in a pitch dark room for 14 hours each night. With this dark therapy, he improved so rapidly that they eased the schedule from 14 hours of darkness to 10 hours each night (10:00 PM to 8:00 AM). He stayed well with that regimen, and that is how dark therapy was 

: But the treatment didn’t really take off. First, it’s hard to get patients in a pitch-dark room overnight. We’re talking so dark that you can’t see your hands in front of your face. Second, we need more than an intriguing case report to put this into practice. The first problem was resolved in the early 2000s by James Phelps, MD.

Phelps was working in private practice in Oregon when he chanced upon 3 discoveries that would open up new therapeutic doors in bipolar disorder. First, he learned about Wehr’s research on dark therapy. Then he learned about the new photoreceptor, melanopsin, that set the circadian rhythm by responding to blue light. He wondered if dark therapy could be accomplished by blocking only the blue wavelength of light, and that brought him to the third piece of the puzzle: blue light filtering glasses. Other fields of medicine had already raised alarms about the hazards of evening blue light (such as increased risk of cancer and heart disease) and a company was manufacturing these to improve sleep and health. Phelps called this 

 and tried the glasses out on his patients. For some, the glasses did nothing, but about half of his patients reported their sleep was better when they wore the glasses 1 to 2 hours before bed.

He then discovered that welders used the same blue-light filters to protect their eyes at the local welding shop, and this opened the door to more treatments because these factory grade lenses were only $7. Phelps tested them and the fit the bill. 

later ran tests of blue light blockers and also concluded that the Uvex safety lenses he was using were among the strongest filters.

Phelps tested the waters, but the definitive study was a full-scale randomized trial in patients who were hospitalized for mania. In addition to treatment as usual, half wore amber lenses in the evening, and half wore (placebo) gray lenses, until sleeping in a pitch-dark room. The improvements were dramatic over the first week, with a large effect size of 1.9, while the control group barely changed.

You don’t need to be in the hospital to do this therapy. Phelps has had success using it in an outpatient practice, and we have as well. Here’s how you do it.

The original protocol required manic patients to be in either pitch darkness or virtual darkness (that is, with the amber glasses on) for 14 hours, from 6:00 PM to 8:00 AM. It took about a week for the mania to improve, and as it did the protocol was relaxed a bit, from 14 hours per night to 10 hours per night. So instead of putting the glasses on at 6 PM, they’d put them on at 7:00 PM, then 8:00 PM, and for prevention thy would move it to 9 or 10 PM. They don’t wear the glasses while asleep. That’s what the pitch-dark bedroom is for. But they do put them on if they are awake and the lights are on.

And the pitch darkness really does matter. Even light as dim as a nightlight on can interfere with melatonin secretion. In a large epidemiologic study of older adults, sleeping with a night light on doubled the risk of depression over 2 years compared to a pitch-dark bedroom.

But how do they get their bedroom pitch dark in this electric light world? 

, electrical tape over LEDs, towels or draft snakes under doors, or sleeping in the basement. If there is still stray light, patients can also sleep with a good eye mask.

: One problem we run into is patients who feel they can’t sleep without the TV on. Usually the reason is depressive rumination. These patients rely on the TV to distract them from their negative, ruminating thoughts. If that’s the case, we recommend ambient music or boring audiobooks instead. Another problem is patients who are afraid of the dark, such as those with PTSD. Here we have a technological solution. They can use amber colored nightlights that don’t emit any blue light. They are available for around $12.

: One modification we don’t recommend is to rely on blue-light filters on laptops and cell phones. Most devices have a setting that turns down the blue in the evening, and no doubt this is certainly a good thing and we’d recommend it in conjunction with dark therapy, but it doesn’t filter 100% and it isn’t going to take care of the background lights. You can find this feature in your smart phone’s settings, or if you’re using a laptop try downloading f.lux (spell it out) for windows or Candlelight by Oliver Denman for Mac.

But what if your patient can’t put the glasses on at 6 PM? Remember the 14-hour protocol was used for hospitalized mania, and they loosened it up as the patient got better. In practice, you might use dark therapy for hypomania, mild mixed states or as an intervention for early signs of mania. In those cases, putting the glasses on 2 hours before bed might be enough.

: It’s also important to set up expectations. Tell your patient that dark therapy is going to help stabilize their mood, but it may not help them fall asleep. Here’s an interesting pearl from that controlled trial. The patients who got better with the dark therapy didn’t actually sleep more. They slept a little less than the placebo group, but their sleep did get more regular. It went from sleeping and waking at random times to a more steady, stable circadian pattern.

 A lot of times patients will give up on dark therapy because they think it is supposed to help them sleep.

: Dark therapy improves mania, but what does it do to sleep? We found 3 randomized controlled trials that tested them out in insomnia, and they had a large effect, helping patients stay asleep longer, fall asleep earlier, and deepening sleep quality.

 One of them used the blue light blockers as an adjunct to CBT-insomnia, where half the patients had the behavioral therapy with placebo glasses and half used the blue-light blockers. Not only did sleep improve with the blockers, but so did anxiety and depression.10 Another study looked at performance on cognitive tests after wearing the glasses, and that got better as well, probably because the patients were sleeping better.

 In the sleep studies, patients put the glasses on 1.5 to 2 hours before bedtime.

Blue light blockers have been used successfully in jet lag, and they tend to help night owls fall asleep earlier.

: I wear them myself and I can attest to that. I’m more patient and have better attention, a little quicker on my feet, the next day if I wore them before bed.

: Blue light blockers have a big effect in mania and rapid cycling, and for sleep they deepen sleep quality and turn night owls into morning people. But can they help depression? We know from animal studies and epidemiologic studies that blue light causes depression, but when it comes to clinical studies using blue light blockers to treat depression the results are mixed. In that CBT-insomnia study, they did improve depressive symptoms, but those patients had clinical insomnia, not clinical depression.

 Beyond that, we have only 2 controlled trials, 1 positive, 1 negative. The positive one was small (n = 27) and centered on postpartum depression, where nocturnal awakening is the norm. Women who used blue-light blockers and low-blue light bulbs had greater improvements than those who used placebo glasses and bulbs.

 The negative study was also small (n = 20) and included depressed patients with insomnia. The investigators suspected that the glasses might not have worked because the patients found them uncomfortable and did not wear them as much as they should.

: When worn at night, blue light filters have beneficial, biological effects, but can they have side effects? Nothing major showed up in the studies. Possibly headaches, and there are reports of depression in some patients. This usually improves by putting the glasses on later, say, 7 PM or 8 PM instead of 6 PM. Although you can see pretty clearly through the glasses, color vision is distorted so we don’t recommend them while driving.

: We have links to recommended brands of blue-light blockers in the text to this podcast. We hope to see you again on 

, and you can also catch us every Monday on the 

is the Mood Disorders Section Editor for 

 He has written several books on mood disorders, most recently

 with his cohost Kellie Newsome, PMH-NP. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for

and is also a practicing psychiatric mental health nurse practitioner in Winston Salem, NC, at the Mood Treatment Center. Raised in Tasmania, Australia, Kellie moved to the United States in 1998.

1. Bedrosian TA, Vaughn CA, Galan A, et al. 

Nocturnal light exposure impairs affective responses in a wavelength-dependent manner.

2. Henriksen TE, Skrede S, Fasmer OB, et al. 

Lunar cycle and psychiatric hospital admissions for schizophrenia: new findings from Henan province, China.

4. Kayumov L, Casper RF, Hawa RJ, et al. 

Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work.

5. Quested DJ, Gibson JC, Sharpley AL, et al. Melatonin In Acute Mania Investigation (MIAMI-UK). 

A randomized controlled trial of add-on melatonin in bipolar disorder.

6. Barbato G, Barker C, Bender C, et al. 

7. Wehr TA, Turner EH, Shimada JM, et al. 

Dark therapy for bipolar disorder using amber lenses for blue light blockade.

Bedroom light exposure at night and the incidence of depressive symptoms: a longitudinal study of the heijo-kyo cohort.

10. Janků K, Šmotek M, Fárková E, Kopřivová J. 

Block the light and sleep well: Evening blue light filtration as a part of cognitive behavioral therapy for insomnia

11. Zimmerman ME, Kim MB, Hale C, et al. 

Neuropsychological function response to nocturnal blue light blockage in individuals with symptoms of insomnia: A pilot randomized controlled study.

12. Shechter A, Kim EW, St-Onge MP, Westwood AJ. 

Blocking nocturnal blue light for insomnia: A randomized controlled trial.

13. Bennett S, Alpert M, Kubulins V, et al. 

Use of modified spectacles and light bulbs to block blue light at night may prevent postpartum depression.

14. Esaki Y, Kitajima T, Takeuchi I, et al. 

Effect of blue-blocking glasses in major depressive disorder with sleep onset insomnia: A randomized, double-blind, placebo-controlled study.

How to regulate circadian rhythms and regulate mood using dark therapy. 

Blue Light Blockers: A Behavior Therapy for Mania

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Antidepressant augmentation is a common practice, and there are many strategies from which to choose. The 

 recommends a menu approach that encourages patients to collaboratively choose an option that best fits their needs.

 In addition to psychotherapy and lifestyle approaches like aerobic exercise, they recommend augmentation with:

1. Natural treatments: omega-3 fatty acids, L-methylfolate, or light therapy

2. Antipsychotics: aripiprazole, risperidone, or quetiapine

3. Antidepressants: bupropion, imipramine, or mirtazapine

When rapid relief is the priority, an antipsychotic might be the best choice. For favorable tolerability, there is bupropion or a natural therapy, and lithium has strong antisuicide effects, if that is a concern. But what if insomnia is the chief complaint? Mirtazapine is tempting here, but this medication carries a risk of weight gain and did not perform well in several recent, well-designed augmentation trials.

 Instead, a standard hypnotic may be a good option when patients continue to have depression and insomnia on an antidepressant, but not just any hypnotic.

Eszopiclone: The Science Behind Its Potential Effect on Depression

In the early 2000s, a group of sleep researchers set out to investigate whether hypnotics could improve mood in patients with depression and insomnia. The results did not pan out exactly as expected, but they point the way toward a medication with unique potential in depression.

But first, investigators had to overcome a hurdle. At the time, it was thought that hypnotics might cause depression through their sedative effects. That concern was partly put to rest in a 1999 study that tested whether zolpidem could relieve selective serotonin reuptake inhibitor [SSRI]-induced insomnia in patients who had otherwise recovered on the antidepressant. The sleep problems improved with zolpidem and, to the investigators’ relief, the sedating medication did not worsen depression.

Buoyed by this result, the manufacturer of eszopiclone funded a large trial to see if depression might actually improve with their hypnotic. Five hundred and forty-five patients with depression and insomnia were randomized to receive either eszopiclone 3mg or placebo while simultaneously starting a trial of fluoxetine. As expected, the hypnotic improved sleep, but it also improved mood symptoms that were unrelated to sleep. Compared to placebo, those who received eszopiclone experienced a more rapid and complete recovery from depression.

The same group repeated the study with zolpidem ER in a large trial of similar design. Once again, the hypnotic improved sleep, but this time there was no change in mood.

 Replication in China brought the same negative results, and last year zolpidem failed again to lift mood or reduce suicidality when added to an SSRI in a randomized trial of patients with depression, insomnia, and suicidality.

Meanwhile, eszopiclone repeated its success, improving mood and insomnia in 2 additional trials, 1 of which involved peri- and postmenopausal women with insomnia and depressive symptoms.

 Generalized anxiety disorder also improved when eszopiclone was added to an SSRI in a large manufacturer-supported trial that replicated the design of eszopiclone’s pivotal depression trial.

A hypnotic might be a good option for augmenting depression treatment, but which hypnotic has the best evidence for efficacy? 