Chronotherapy Offers Promising Results in Depression

Sleep research: series of false-colour traces showing brain & muscle activity during rapid eye movement (REM) sleep. Sleep comprises cycles of 5 stages: 1-4 are stages of increasingly deeper, non-rapid eye movement (NREM) sleep, with REM sleep following as stage 5. Electrical activity is lowest during stage 4. Numbering the traces from top to bottom, 1 & 2 are electroencephalograms (EEG) of brain activity; 3 is an electrooculogram (EOG) of movement in the right eye; 4 an EOG of the left eye; 5 is an electrocardiogram (ECG) trace of heart activity. 6 & 7 are electromyograms (EMG) of activity in the laryngeal (6) and neck (7) muscles.
Compared with other therapies alone, including psychotherapy, antidepressant medication, exercise, or therapy, chronotherapy was more effective at days 5 to 7.

Chronotherapy, a noninvasive, nonpharmacological intervention, appears to be effective for the rapid treatment of depression, according to a study published in the Journal of Affective Disorders. Clara Humpston, PhD, from the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, United Kingdom, and colleagues performed a meta-analysis of treatments involving sleep deprivation, sleep phase shifting, and/or bright light exposure to target depressive symptoms.

The analysis included both randomized controlled and open-label trials taken from the PubMed, EMBASE, PsychINFO, and CINAHL databases. To be eligible, studies had to be in English, published in peer-reviewed journals, available in full-text version, and include patients with a diagnosed depressive episode (unipolar or bipolar) at the time of the study. Inclusion criteria also required that trials involve experimentally induced partial or total sleep deprivation followed by sleep phase advance or delay, with or without light therapy, in an adult population diagnosed with a depressive episode at the time of study. In total, 16 studies were selected for the final analysis.

Compared with other therapies alone, such as psychotherapy, antidepressant medication, exercise, or therapy, chronotherapy was more effective at days 5 to 7 posttreatment, and effect sizes immediately after treatment (day 1-2) were very strong. Results from the randomized controlled trials demonstrated that chronotherapy was superior at day 5 to 7 (g=0.62; 95% CI, 0.23-1.01) compared with control treatments, specifically antidepressants and exercise. Of the patients in the chronotherapy group, 33.0% were responders, whereas 1.5% of patients in the control condition were considered responders.

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Similarly, results from open-label case series demonstrated the effectiveness of chronotherapy (g=1.79; 95% CI, 1.50-2.08), and 61.6% of patients were considered responders. In a secondary analysis comparing unipolar and bipolar patients, both groups demonstrated similar effect sizes.

Longer-term follow-up data from randomized controlled trials suggested a possible diminished effect of chronotherapy over time, although this attenuation was contested by results from open case trials, which demonstrated a sustained effect. Only 1 study reported any adverse effects.

The meta-analysis is limited by the relatively small number of randomized controlled trials, as well as a high level of heterogeneity of patient populations. Nearly all the included studies focused on inpatients; results may not be generalizable to outpatients.

The study authors wrote, “Compared with routine treatments such as medication, talking therapy or exercise, chronotherapy has the added benefit of rapid treatment response in addition to a highly favourable side effect profile.” They also called for future studies to identify circadian rhythm markers of response and to lengthen follow-up periods to determine long-term efficacy.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Humpston C, Benedetti F, Serfaty M, et al. Chronotherapy for the rapid treatment of depression: A meta-analysis. J Affect Disord. 2020;261:91-102.