Circadian antidepressant treatments in depression: A systematic review and meta-analysis

The purpose of the present study was to explore whether maximum efficacy treatments would be dependent on the time of day at which antidepressants were taken. Databases were searched for randomized experiments or randomized controlled trials involving interventions of any antidepressants taken at a particular time of the day. Out of 10 348 screened articles, 10 studies were included in the meta-analyses. The optimal time of maximum efficacies in 5 out of 15 drugs in the 10 studies was at zeitgeber time (ZT) 2, including fluoxetine, sertraline, citalopram, doxepin, and agomelatine. The best therapeutic effects of mirtazapine, trazodone, and agomelatine were at ZT10, while maximum efficacies of venlafaxine and fluvoxamine were at ZT6 and ZT13, respectively. The optimal time of melatonin administration was the period of treatment dependence. We found antidepressants with different mechanisms might have same or different optimal administration times. These findings may guide evidence-based antidepressant treatment choices with optimal dosing time. More prospective randomized trials or randomized experiments are demanded to establish recommendations for optimal circadian timing of depression based on zeitgeber time. It would be of interest to further evaluate this time-selection as a potential viable novel therapeutic in future research.