J Am Acad Child Adolesc Psychiatry. 2024 Aug 7:S0890-8567(24)01316-9. doi: 10.1016/j.jaac.2024.07.920. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare second-generation antipsychotics (SGAs) and mood stabilizers (MSs) in youth with a bipolar disorder type-1 (BD-I) manic/mixed episode.

METHOD: Systematic PubMed/Embase/PsycInfo literature search until 12/31/2023 for randomized trials of SGAs or MSs in patients aged ≤18 years with BD-I manic/mixed episode. Network meta-analysis comparing treatments regarding mania symptoms and mania response (co-primary outcomes), and secondary efficacy and tolerability outcomes.

RESULTS: Eighteen studies (n=2844, mean age=11.74, females=48.0%, mean study duration=5.4 weeks) comparing six SGAs (aripiprazole, asenapine, olanzapine, quetiapine, risperidone, ziprasidone) and four MSs (lithium, oxcarbazepine, topiramate, valproate) were meta-analyzed. All six SGAs outperformed placebo in reducing manic symptomatology, including risperidone (SMD=-1.18,95%CI=-0.92;-1.45, CINeMA= moderate confidence), olanzapine (SMD=-0.77,95%CI=-0.36;-1.18, low confidence), aripiprazole (SMD=-0.67,95%CI=-0.33;-1.01, moderate confidence), quetiapine (SMD=-0.60,95%CI=-0.32,-0.87, high confidence), asenapine (SMD=-0.54,95%CI=-0.19; -0.89, moderate confidence), and ziprasidone (SMD=-0.43,95%CI=-0.17-0.70, low confidence), while no mood stabilizer outperformed placebo. Concerning mania response, risperidone (RR=2.58,95%CI=1.88;3.54, low confidence), olanzapine (RR=2.42,95%CI=1.33-3.54, very low confidence), aripiprazole (RR=2.05,95%CI=1.44-2.92, low confidence), quetiapine (RR=1.89,95%CI=1.45-2.47, moderate confidence), asenapine (RR=1.81,95%CI=1.28-2.55, very low confidence) and lithium (RR=1.35,95%CI=1.00;1.83, p-value=0.049, very low confidence) outperformed placebo, without superiority of other MSs versus placebo. Individually, risperidone was more efficacious in reducing manic symptomatology than all other comparators, except olanzapine and topiramate, yet with low/very low confidence, and was associated with increased prolactin and glucose. Pooled together, SGAs outperformed both placebo and MSs for mania symptoms reduction (SMD=-0.68,95%CI=-0.86;-0.51 and SMD=-0.61,95%CI=-0.82;-0.40, moderate confidence), and mania response (RR=1.85,95%CI=1.53;2.24 and RR=1.65,95%CI=1.33-2.04, moderate confidence) without differences between MSs and placebo. There were no significant treatment-placebo differences for all-cause discontinuation, while lithium, ziprasidone and oxcarbazepine were associated with more adverse event-related drop-outs than placebo. Most SGAs were associated with more sedation, weight gain, and metabolic issues versus placebo and MSs.

CONCLUSION: SGAs are more efficacious than placebo and MSs in treating acute mania symptoms, however, their use must be carefully weighed against important side effects.

PMID:39128561 | DOI:10.1016/j.jaac.2024.07.920