No comprehensive meta-analysis has been performed concerning the efficacy and tolerability of Z-drug adjunctive
therapy in
antidepressant-treated
major depressive disorder (MDD) patients. Randomized, placebo-, or
antidepressant-alone-controlled trials of Z-drugs in MDD patients were included. The primary outcome measures for efficacy and safety were remission rate and all-cause discontinuation, respectively. The secondary outcome measures were response rate, Hamilton Depression Rating Scale (HAMD) total score improvement, discontinuation due to inefficacy and adverse events, and individual adverse effects. Risk ratio (RR), number needed to treat/harm (NNT/NNH), 95 % confidence intervals, and standardized mean difference (SMD) were calculated. We identified six studies [
antidepressants were
selective serotonin reuptake inhibitors and
venlafaxine, mean duration of study was 10.5 weeks, mean age of patients (mean ± standard deviation) was 44.4 ± 11.8 years old, total n = 2089, eszopiclone + antidepressants = 642, placebo + antidepressants = 930,
antidepressants alone = 112, and zolpidem + antidepressants = 405]. Pooled Z-drug + antidepressants was superior to placebo + antidepressants regarding the remission rate (RR = 0.85, NNT = 10). Although pooled Z-drug + antidepressants was also superior to placebo + antidepressants/
antidepressants alone regarding HAMD score improvement (SMD = -0.23), there was not significant difference in response rate and discontinuation due to inefficacy between groups. There was no difference in all-cause discontinuation between groups. Although there was also no difference in discontinuation due to adverse events between groups, pooled Z-drug + antidepressants was associated with a higher incidence of at least one adverse event (RR = 1.09, NNH = 20) and
dizziness (RR = 1.76, NNH = 25) compared with the placebo + antidepressants/
antidepressants alone. In conclusion, Z-drugs + antidepressants improves the treatment efficacy for MDD compared with the placebo + antidepressants/
antidepressants alone. However, the
therapy requires close monitoring of adverse events, particularly
dizziness.