We searched the Cochrane Common
Mental Disorders Controlled Trials Register (CCMDCTR-Studies and CCMDCTR-References) to 17 August 2015. The CCMDCTR contains reports of relevant RCTs from MEDLINE (1950-), Embase (1974-), PsycINFO (1967-) and CENTRAL (all years). We scanned the reference lists of articles for additional studies. We updated the search in August 2017 and placed additional studies in Awaiting Classification, these will be incorporated in the next version of the review, as appropriate.
SELECTION CRITERIA: Two authors (TW and JI) assessed trials for eligibility and inclusion for this review update. We extracted descriptive, methodological and outcome information from each trial, contacting investigators for missing information where necessary. We calculated summary statistics for continuous and dichotomous variables (if provided) and undertook subgroup and sensitivity analyses.
MAIN RESULTS: We included 66 RCTs in the review (> 24 weeks; 11,597 participants; age range 18 to 70 years) and 63 in the meta-analysis. For the primary outcome of treatment response, we found very low-quality evidence of treatment response for
selective serotonin reuptake inhibitors (
SSRIs) compared with placebo (number of studies (k) = 24, risk ratio (RR) 1.65; 95% confidence interval (CI) 1.48 to 1.85, N = 4984). On this outcome there was also evidence of benefit for
monoamine oxidase inhibitors (MAOIs) (
k = 4, RR 2.36; 95% CI 1.48 to 3.75, N = 235),
reversible inhibitors of monoamine oxidase A (RIMAs) (k = 8, RR 1.83; 95% CI 1.32 to 2.55, N = 1270), and the
benzodiazepines (k = 2, RR 4.03; 95% CI 2.45 to 6.65, N = 132), although the evidence was low quality. We also found clinical response for the
anticonvulsants with gamma-amino
butyric acid (
GABA) analogues (k = 3, RR 1.60; 95% CI 1.16 to 2.20, N = 532; moderate-quality evidence). The
SSRIs were the only medication proving effective in reducing relapse based on moderate-quality evidence. We assessed tolerability of
SSRIs and the
serotonin and
norepinephrine reuptake inhibitor (
SNRI)
venlafaxine on the basis of treatment withdrawal; this was higher for medication than placebo (
SSRIs: k = 24, RR 2.59; 95% CI 1.97 to 3.39, N = 5131, low-quality evidence;
venlafaxine:
k = 4, RR 3.23; 95% CI 2.15 to 4.86, N = 1213, moderate-quality evidence), but there were low absolute rates of withdrawal for both these medications classes compared to placebo. We did not find evidence of a benefit for the rest of the medications compared to placebo.For the secondary outcome of
SAnD symptom severity, there was benefit for the
SSRIs, the
SNRI venlafaxine, MAOIs, RIMAs,
benzodiazepines, the
antipsychotic olanzapine, and the noradrenergic and specific serotonergic
antidepressant (NaSSA)
atomoxetine in the reduction of
SAnD symptoms, but most of the evidence was of very low quality. Treatment with
SSRIs and RIMAs was also associated with a reduction in depression symptoms. The
SSRIs were the only medication class that demonstrated evidence of reduction in disability across a number of domains.We observed a response to long-term treatment with medication for the
SSRIs (low-quality evidence), for the MAOIs (very low-quality evidence) and for the RIMAs (moderate-quality evidence).
AUTHORS' CONCLUSIONS: We found evidence of treatment efficacy for the
SSRIs, but it is based on very low- to moderate-quality evidence. Tolerability of
SSRIs was lower than placebo, but absolute withdrawal rates were low.While a small number of trials did report treatment efficacy for
benzodiazepines,
anticonvulsants, MAOIs, and RIMAs, readers should consider this finding in the context of potential for abuse or unfavourable side effects.