Efficacy of Triple Chronotherapy in unipolar and bipolar depression: A systematic review of the available evidence

Background: Given the strong relationship between circadian rhythm disruption and mood regulation, combined chronotherapeutic approaches have been proposed for mood disorders. However, a comprehensive review of the available evidence on the efficacy of such interventions for depression is lacking. Aim: To systematically review available literature on Triple Chronotherapy (Sleep Deprivation – Sleep Phase Advance – Bright Light Therapy) for depressive symptoms in Major Depression and Bipolar Depression. Methods: We followed the PRISMA statement for systematic reviews to conduct a web-based search on PubMed, Scopus and Embase using a list of selected keywords relevant to depression and chronotherapy. Results: After title and abstract screening of the 321 records retrieved, 25 potentially eligible studies were assessed at full-text screening. Nineteen studies were excluded for failure to match inclusion criteria. Six records of Triple Chronotherapy in addition to conventional treatment, published between 2009 and 2018, were included in the revision. All studies reported significant improvements on HAM–D scores at the end of treatment, with 50% to 84% response rates. Efficacy of treatment was confirmed on follow-up by three studies, with 58% to 61% response rates. Remission rates varied from 33,3% to 77%. Reported side effects were negligible across studies. Limitations: Available trials are very few and only one included a control group treated with a daily exercise program. Conclusions: The limited literature suggests that Triple chronotherapy might be a safe and effective addition to conventional antidepressant interventions, although well–designed, randomized controlled trials are needed.