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 2019, 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.

[Triple Chronotherapy approach for reducing depressive symptoms and suicidal intent in hospitalized patients: Study protocol of a Randomized Controlled Trial]. / La Triple Chronotherapy come approccio per la riduzione della sintomatologia depressiva e dell'intenzionalità suicidaria in pazienti ospedalizzati: Protocollo di studio di un Trial Clinico randomizzato controllato.

BACKGROUND: Depressive disorders are a relevant burden for public health due to their prevalence and high levels of associated disability and mortality. Recent studies suggest that the combination of multiple chronotherapuetic interventions may reveal effective in the rapid improvement of depressive symptoms. OBJECTIVES: This paper describes the protocol of a study that aims to test the efficacy of a triple chronotherapy intervention (combined total sleep deprivation, light therapy and sleep phase advance) in the improvement of depressive symptoms in individuals diagnosed with unipolar or bipolar depression. METHODS: A randomized controlled trial will be conducted in patients hospitalized with a unipolar or bipolar depression at the Servizio Psichiatrico di Diagnosi e Cura inpatient unit of the San Paolo - ASST Santi Paolo e Carlo Hospital in Milan, Italy. Individuals will be randomly assigned to the intervention (triple chronotherapy add-on to standard pharmacological treatment) or to the "control" group (standard pharmacological treatment). RESULTS: Enrolment began in December 2018 and will end in October 2020, or at any earlier point in which the expected sample size will be reached. The study protocol has already been approved by the local ethics committee and is registered as EudraCT 2019-000892-18. Outcome analyses aim to verify whether triple chronotherapy produces a rapid and stable improvement in depressive symptoms in individuals hospitalized for an acute unipolar or bipolar depressive episode.