While clinical trial evidence has firmly established the efficacy of several atypical
antipsychotics (AAPs) for treating
bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of
AAP monotherapy in adults with
bipolar depression.
METHODS: Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement -
Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated.
RESULTS: Eighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS,
lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]),
quetiapine (- 4.80 [- 5.93, - 3.72]),
olanzapine (- 4.57 [- 5.92, - 3.20]), and
cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo.
Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to
cariprazine (1.78 [95% Crl 1.08, 2.77]),
aripiprazole (2.38 [1.38, 3.85]), and
ziprasidone (2.47 [1.41, 3.98]), but was similar to
olanzapine (1.68 [0.99,2.65]) and
quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score,
lurasidone was significantly better than
cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and
ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to
quetiapine (- 0.08 [- 0.36, 0.19])and
olanzapine (- 0.04 [- 1.41, 1.46]).
Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and
aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but
olanzapine (2.88 kg [2.40, 3.36]),
quetiapine (1.17 kg [0.84, 1.49]), and
cariprazine (0.65 kg [0.34, 0.96]) were associated with greater
weight gain. The NNT for response was the lowest for
lurasidone (NNT = 5) followed by
quetiapine (NNT = 6),
olanzapine (NNT = 10) and
cariprazine (NNT = 12).
CONCLUSIONS: