J Affect Disord. 2022 Jan 2:S0165-0327(21)01451-8. doi: 10.1016/j.jad.2021.12.134. Online ahead of print.
ABSTRACT
OBJECTIVE: To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents.
METHODS: We included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Twenty-one agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, mood stabilizers and olanzapine-fluoxetine combination. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model.
RESULTS: A total of 63 studies (N=12108) with 21 augmentation agents were included. Our findings from the NMA for response rates, compared to placebo, were significant for: liothyronine, nortriptyline, aripiprazole, brexpiprazole, quetiapine, lithium, modafinil, olanzapine+fluoxetine, cariprazine, and lisdexamphetamine. For remission rates, compared to placebo, were significant for: statistically higher findings were found for: thyroid hormone(T4), aripiprazole, risperidone, quetiapine, and olanzapine+fluoxetine. Compared to placebo, ziprasidone, mirtazapine, and cariprazine had statistically significant higher discontinuation rates. Overall, 24% studies were rated as having low risk of bias(RoB), 63% had moderate RoB and 13% had high RoB.
LIMITATIONS: Heterogeneity in TRD definitions, variable trial duration and methodological clinical design of older studies and small number of trials per comparisons.
CONCLUSIONS: In reviewing more than 20 studies this NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamphetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.
PMID:34986373 | DOI:10.1016/j.jad.2021.12.134
