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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.
RESUMO
Objective: To identify outcome predictors in hospitalized youth with mental disorders.Methods: This retrospective analysis of systematically recorded clinical parameters in youth hospitalized for psychiatric treatment in 2004-2015 assessed magnitude and correlates of symptom response (SR), global illness response (GIR), social functioning (SF), out-of-home placement (OOHP), and length of stay (LOS). Backward elimination regression analyses were performed to identify independent baseline correlates of each of the 5 outcomes, with R2 representing the variance explained by the independent correlates retained in the final model.Results: Across 1,189 youth (median age = 14.4 years; interquartile range = 11.6,16.1 years; range, 5-19 years; females = 61.5%), frequencies of coprimary outcomes were as follows: SR = 57.5% (statistically significant correlates = 13, R2 = 0.154), GIR = 30.0% (correlates = 5, R2 = 0.078), SF = 19.0% (correlates = 8, R2 = 0.207), OOHP recommendation = 35.2% (correlates = 13, R2 = 0.275), and mean ± SD LOS = 65.0 ± 37.5 days (correlates = 11, R2 = 0.219). In multivariable analyses, 11 factors were statistically significantly (P < .05) associated with > 1 poor outcome: 4 with 4 outcomes (disturbed social interaction, substance abuse/dependence symptoms; sole exception for both = LOS; disturbed drive/attention/impulse control, sole exception = OOHP; higher admission BMI percentile [but shorter LOS], sole exception = GIR), 3 with 3 outcomes (higher admission age [but good SF and shorter LOS], more abnormal psychosocial circumstances, more mental health diagnoses), and 4 with 2 outcomes (intelligence level [IQ] < 85, obsessive-compulsive disorder symptoms, disturbed social behavior, somatic findings). Additionally, 17 correlates were statistically significantly (P < .05) associated with 1 outcome, ie, SR = 6, OOHP = 5, LOS = 5, SF = 1.Conclusions: Higher admission BMI percentile, disturbed social interaction, disturbed drive/attention/impulse control, and substance abuse/dependence symptoms were independently associated with multiple poor outcomes in mentally ill youth requiring inpatient care. Knowledge of global and specific correlates of poor inpatient treatment outcomes may help inform treatment decisions.