Sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitor antidepressants: Secondary analyses of the GENPOD trial.

BACKGROUND: Differences in serotonergic neurotransmission could lead to sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitors (SSRIs). AIMS: We investigated whether women have greater reductions in depressive symptoms than men after treatment with an SSRI (citalopram) compared with a noradrenaline reuptake inhibitor (reboxetine) control, and after antidepressant treatment irrespective of class. We also investigated tolerability and the influence of menopausal status. METHODS: Secondary analyses of the GENPOD (GENetic and clinical Predictors Of treatment response in Depression) trial. Six hundred and one people with depression were recruited from UK primary care and randomized to citalopram or reboxetine. Beck Depression Inventory (BDI-II) score at 6 weeks was the primary outcome. Secondary outcomes included BDI-II score at 12 weeks, and physical symptoms and treatment discontinuation. We calculated main effects and interaction terms using linear and logistic regression models. RESULTS: There was no evidence that women experienced greater reductions in depressive symptoms than men when treated with citalopram compared with reboxetine. We also found no evidence of sex differences at six or 12 weeks (irrespective of antidepressant class): men scored -0.31 (95% confidence interval (CI) -2.23 to 1.62) BDI-II points lower than women at six weeks and -0.44 (95% CI -2.62 to 1.74) points lower at 12 weeks. There was no evidence of sex differences in physical symptoms or treatment discontinuation and no evidence for an influence of menopausal status. CONCLUSION: Citalopram was not more effective in women compared with men and there was no difference in tolerability. Women and men had similar prognosis after SSRI treatment and similar prognosis regardless of antidepressant class. Findings were unaltered by menopausal status.

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.