https://www.selleckchem.com/products/unc5293.html To determine the relative variability and magnitude of symptomatic improvement in antidepressant-treated individuals compared to placebo-treated individuals, and to investigate moderating factors. Multiple databases and previous publications were searched through February 2019 to identify all randomized controlled trials comparing placebo and antidepressants in acute treatment of depression. Primary outcome was relative variability of change in symptom severity in antidepressant-treated individuals compared to placebo-treated patients quantified using the coefficient of variation ratio (CVR). Of 9389 identified records, 134 were found to be eligible (total n = 46,646). Antidepressant-treated patients showed a significantly greater magnitude (g = 0.28, 95% CI 0.25-0.30, p < .0001) and lower variability (CVR = 0.94, 95% CI 0.93-0.95, p < .0001) of change in symptom severity relative to placebo-treated patients. Compared to placebo antidepressant-related improvement was more uniform in older studies ur results in-stead suggest that antidepressants show a relatively uniform effect. The definitions of treatment-resistant bipolar disorder (TRBD) have varied across studies. Additionally, its management is clinically challenging. An updated synthesis and appraisal of the available evidence is needed. A systematic search of major electronic databases from inception up to May 25th, 2020, was conducted to identify randomized controlled trials (RCTs) of pharmacological and non-pharmacological interventions for the management of TRBD. When sufficient evidence was available, a meta-analysis was conducted. Seventeen studies (n=928 patients) were included in the qualitative synthesis. Fourteen studies (n=803) assessed treatment-resistant acute bipolar depression (TRBD-De), including five neuromodulatory and nine pharmacological trials. Rapid- vs. standard up-titration of clozapine showed promising efficacy for TRBD mania, without si