Efficacy and tolerability of atypical antipsychotics for acute bipolar depression: a network meta-analysis

Abstract

Background 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 In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.

Mortality in people with schizophrenia: a systematic review and meta‐analysis of relative risk and aggravating or attenuating factors

“…While the anti-suicidal efficacy of clozapine has been established 188 , the differential finding favoring SGAs may be due to the fact that suicide in schizophrenia is often associated with the emergence of depression 168 . FGAs do not improve or even induce depressive symptoms, while many SGAs have been shown to be effective in treating these symptoms [189][190][191] .…”

Dopamine Receptor Partial Agonists: Do They Differ in Their Clinical Efficacy?

“…In a network meta-analysis of the efficacy and tolerability of second-generation antipsychotic monotherapy in acute bipolar depression, the only DRPA more efficacious than placebo was cariprazine; aripiprazole was not separated from placebo ( 72 ). The mean change in the MADRS total score for cariprazine was −2.29 (95% CI −3.47, −1.09), and the odds ratio for response (≥50% improvement in the MADRS) was 1.47 (95% CI 1.17, 1.82).…”

Risk of Drug-induced Movement Disorders with Newer Antipsychotic Agents

“…NNH for akathisia is estimated to be ~30 for cariprazine, 34 for quetiapine, and 15 for lurasidone (n = 1407) [ 46 ]. A network meta-analysis (n = 4324) of multiple RCTs showed that there was no significant difference in overall rates of DIMD comparing aripiprazole, quetiapine, cariprazine, and lurasidone but surface under cumulative ranking curves (SUCRA) demonstrate reduced risk of DIMD for aripiprazole (overall DIMD 0.57, akathisia 0.51) and cariprazine (overall DIMD 0.45, akathisia 0.38) relative to quetiapine (overall DIMD 0.28) and lurasidone (overall DIMD 0.22, akathisia 0.13) [ 48 ]. Cariprazine may be more prone to causing akathisia, particularly early in treatment, relative to aripiprazole and risperidone while overall DIMD rates are intermediate among SGAs.…”