Sleep Deprivation a Rapid, Effective Depression Treatment

Nancy A. Melville

September 27, 2017

Sleep deprivation therapy consistently shows a rapid, albeit short-lived, reduction in depressive symptoms in up to half of patients with the disorder, a new meta-analysis suggests.

Although these effects are short-lived, they are intriguing enough to continue to generate interest in how to sustain the response, investigators, led by Philip R Gehrman, PhD, University of Pennsylvania, in Philadelphia, note.

"The availability of an antidepressant treatment that has rapid effects in 50% of patients would mark a radical improvement in clinical practice, if we can find ways to maintain the effects over time," they investigators write.

"The short-lived response is one of the reasons sleep deprivation is not routinely used outside of research protocols," Dr Gehrman told Medscape Medical News.

The researchers report that this is the first quantitative analysis of this therapeutic approach in more than a decade.

The findings were published online September 19 in the Journal of Clinical Psychiatry.

Rarely Used in Depression

The potential antidepressant effects of sleep deprivation have long been explored, with reports commonly showing response rates of 40% to 70%. Although sleep restriction is sometimes used as a component of insomnia treatment, its use as a treatment for depression is rare.

The last quantitative review of research into its antidepressant effects dates back to 1990. Since then, up to 75 new studies assessing sleep deprivation have been published, with wide variation in study design and patient populations.

To take a closer look at the evidence since the last analysis, the investigators conducted a quantitative meta-analysis of 66 studies that met inclusion criteria.

Consistent with previous findings, overall results show that approximately 50% of the 1593 participants with depression demonstrated a positive affective response during a 36-hour treatment period. The response rate was 45% among 141 participants in randomized controlled trials.

The consistency remained despite varying definitions of response. The most common was a 30% reduction in depression severity.

Treatment involving a partial night of sleep deprivation was no less effective than with a full night. Consistent with previous findings, use of antidepressant medications was not associated with either added benefit or reduced efficacy.

"Although some qualitative reviews have suggested that sleep deprivation may be slightly more effective in bipolar samples, our results indicated inferior, although not significantly so, results in bipolar patients relative to unipolar patients," the authors write.

However, they caution that these findings were inconclusive.

"It would be conclude that sleep deprivation is not an effective treatment for bipolar depression," the authors note.

Overall, the findings show notable consistency of response despite numerous differences in important variables.

"Thus, no matter how response is quantified, how sleep deprivation is delivered, or whether the patient has bipolar or unipolar depression, sleep deprivation has a nearly equivalent response rate," the authors write.

Potential Mechanism

A "late" partial sleep deprivation approach, involving deprivation of sleep during the latter 4 hours of the night, is generally considered more effective than "early" deprivation during the first four hours.

However, the new analysis was unable to compare the two approaches because 14 of 15 studies using partial sleep deprivation utilized late partial sleep deprivation only.

Although most studies suggest that the severity of depression does not influence response, the investigators were unable to assess this measure.

Despite the consistent response rates, a glaring caveat of sleep deprivation therapy is the very short duration of response. Most improvement is typically lost after the next full night of sleep, with research showing 80% of responders experience relapse.

Nevertheless, the improvements have prompted efforts to somehow prolong the response, mostly with the use of combined therapies.

Dr Gehrman noted that the new analysis excluded 16 studies that examined therapies combined with sleep deprivation in order to focus specifically on the effects of sleep deprivation by itself.

"There are a number of studies that were not included in our meta-analysis that combined sleep deprivation with other techniques called chronotherapeutics ― for instance, bright light exposure or sleep phase advance ― in an effort to prolong the response. And these studies have shown some success in that endeavor," he said.

One recent meta-analysis of light therapy alone and in combination with sleep deprivation suggested efficacy in improved severity of illness, particularly among patients with bipolar disorder. Another strategy that has been examined is the use of repeated sleep deprivation.

Of studies excluded in the current analysis, the majority included patients with bipolar disorder who were often administered repeated sessions of sleep deprivation. Response rates ranged from 45% to 79%, the authors report.

"Thus, taken together, it may be that individuals with bipolar disorder are more likely to benefit from sleep deprivation when it is administered with chronotherapy over a series of administrations, but this cannot be determined based on the currently available literature base," they write.

One theory for the mechanism by which sleep deprivation reduces depressive symptoms is that the effects may be brought about by a "resetting" of the body's circadian rhythms as a result of CLOCK gene transcription, the investigators note.

Other studies suggest effects on specific brain regions, such as the medical prefrontal cortex or ventral anterior cingulate cortex, and neurotransmitter systems. However, wide variance in study biomarkers and neuroimaging methods prevent an accurate assessment.

Ultimately, the authors speculate that the consistent response of 45% to 50% points to specific phenotypes as likely predictors of response.

"Variability among studies notwithstanding, the stability of this [response rate] across decades and laboratories suggests that the response to sleep deprivation in depressed individuals may be phenotypic, which has not been given adequate consideration," they write.

"To determine whether this is the case, one would ideally study sleep deprivation in depressed individuals at least 2 or more times, utilizing intraclass correlations to establish the degree of phenotypic (stable within-subject) variability in response," the researchers write. "To our knowledge, such a study has not yet been reported," they add.

Relapse Rate Curbs Enthusiasm

Commenting on the findings for Medscape Medical News, Daniel F. Kripke, MD, emeritus professor of psychiatry at the University of California, San Diego, described the analysis an "excellent summary" of sleep deprivation research for depression.

"The conclusion that the response rate is about 50% is consistent with previous studies. This is an extremely large response rate as compared with pharmacologic and psychotherapy responses, referenced to control placebo, and much more rapid," he told Medscape Medical News.

"On the other hand, the fact that most patients relapse after the following night's sleep has spoiled any enthusiasm among most US psychiatrists."

As noted by the investigators, Dr Kripke underscored the fact that sleep deprivation therapy is already practiced as a component of cognitive-behavioral treatment of insomnia (CBT-I) and has been shown to benefit patients with depression in that context.

"Sleep restriction is one of the most important elements of CBT-I," he said. "Initially, this induces some reduction in total sleep time ― though after several weeks, total sleep time may recover or even improve."

He added that other combination-therapy studies are crucial in understanding the full potential of sleep deprivation therapy.

"The major limitation of the meta-analysis, like many meta-analyses, is that it excludes some worthwhile studies, particularly the studies of using bright light and chronobiologic methods to sustain the responses," Dr Kripke said.

One recent study, which was the focus of an editorial by Dr Kripke, showed significant improvements in depressive symptoms when light therapy was combined with the antidepressant venlafaxine. The effects of 1 week of light therapy persisted through 8 weeks.

He noted that several of the study's authors have recommended exploring a "triple therapy" approach that also incorporates sleep restriction.

"Certainly, the recent studies of efforts to sustain the response with bright light and chronobiologic interventions are exceptionally encouraging and seem to indicate that the rapid and valuable responses can be maintained with simple additions to the sleep deprivation. This is what is important in current research." However, much more work is needed, he said.

"Missing from the scientific literature are adequate comparative trials showing whether a single half-night or full-night sleep deprivation adds to light treatment after 8-week or 16-week follow-up or longer, whether the circadian phase shift adds to light, and whether the triple combination is better than combinations of two of these treatments," said Dr Kripke.

The study was funded by grants from the National Institutes of Health, the National Aeronautics and Space Administration, the National Heart, Lung, and Brain Institute, the National Institute on Drug Abuse, the Office of Naval Research, the National Space Biomedical Research Institute, Merck; and Philips Healthcare/Respironics. The study authors and Dr Kripke have disclosed no relevant financial relationships.

J Clin Psychiatry. Published online September 19, 2017. Abstract

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