Lower rate of depressive switch following antimanic treatment with second-generation antipsychotics versus haloperidol.

BACKGROUND: Treatment of acute mania with second-generation antipsychotics has been claimed to involve a lower risk of switch to depression than haloperidol. However, clinical guidelines clearly state that this is not a proven fact. METHODS: Meta-analysis of double-blind randomized controlled trials in acute mania, comparing rates of switch to depression with atypical antipsychotics and with haloperidol. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011). RESULTS: 8 randomized clinical trials fulfilled inclusion criteria. 2 of them were excluded because of low methodological quality or lack of data. 5 second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone) were compared to haloperidol. In the mixed effects model the Risk Ratio for depressive switch was 0.71 (0.52, 0.96) favouring atypical antipsychotics. In the random effects model the difference did not reach statistical significance. In the heterogeneity analysis, exclusion of an outlying aripiprazole trial yielded a Risk Ratio of 0.58 (0.42, 0.82) with a non-significant heterogeneity test. Although no atypical antipsychotic was individually significantly superior to haloperidol, a trend could be seen favouring olanzapine (RR=0.56 [0.29, 1.08]), quetiapine (RR=0.36 [0.10, 1.33]), and ziprasidone (RR=0.51 [0.22, 1.18]). LIMITATIONS: All trials were industry supported, with some variability in dosage of haloperidol. Switch to depression was not the primary outcome of the trials. Heterogeneity could be explained as a lack of class-effect for atypicals. CONCLUSIONS: Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.

Faster onset of antimanic action with haloperidol compared to second-generation antipsychotics. A meta-analysis of randomized clinical trials in acute mania.

BACKGROUND: there is a lack of scientific data regarding speed of action of antimanic treatments, a relevant issue in clinical practice. OBJECTIVE: to assess differences in the speed of onset of antimanic efficacy between haloperidol (as most studied first-generation antipsychotic) and second-generation antipsychotics. EXPERIMENTAL PROCEDURES: meta-analysis of double-blind randomized clinical trials in acute mania, comparing treatment with haloperidol and with second-generation antipsychotics. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011). Differences in mania scale score reduction at week 1 were assessed. RESULTS: 8 randomized clinical trials fulfilled inclusion criteria and 1 of them was excluded due to low methodological quality. 2037 Manic patients had been treated with antipsychotics in the 7 trials. Haloperidol was found to be significantly more efficacious in the reduction of the mania scale score at week 1. The effect size was small, the Standardized Mean Difference (SMD) being 0.17, with a 95% Confidence Interval ranging from 0.01 to 0.32. Haloperidol was significantly more efficacious than olanzapine (SMD: 0.40 [0.21, 0.59]) and ziprasidone (0.39 [0.18, 0.61]). A non-significant trend towards superiority of haloperidol was found over aripiprazole (SMD: 0.13 [-0.02, 0.19]). There were no significant differences between haloperidol and quetiapine (0.17 [-0.11, 0.44]), and haloperidol and risperidone (SMD: -0.10 [0.30, 0.09]). CONCLUSIONS: haloperidol shows a faster onset of antimanic action than second-generation antipsychotics. This difference may be related to D2 affinity. Haloperidol may be considered a treatment option in severely ill manic patients who require urgent relief of symptoms.

Predominant recurrence polarity among 928 adult international bipolar I disorder patients.

OBJECTIVE: To test the hypothesis that patients with bipolar disorder (BPD) differ demographically and clinically within subgroups based on the predominant-polarity of major recurrences. METHOD: We tested factors for association with predominantly (≥2 : 1) depressive vs. mania-like episodes with 928 DSM-IV type-I BPD subjects from five international sites. RESULTS: Factors preliminarily associated with predominant-depression included: electroconvulsive treatment, longer latency-to-BPD diagnosis, first episode depressive or mixed, more suicide attempts, more Axis-II comorbidity, ever having mixed-states, ever married, and female sex. Predominant-mania was associated with: initial manic or psychotic episodes, more drug abuse, more education, and more family psychiatric history. Of the 47.3% of subjects without polarity-predominance, risks for all factors considered were intermediate. Expanding the definition of polarity-predominance to ≥51% added little, but shifting mixed-states to 'predominant-depression' increased risk of suicidal acts from 2.4- to 4.5-fold excess over predominant-mania-hypomania, and suicidal risk was associated continuously with increasing proportions of depressive or mixed episodes. CONCLUSION: Subtyping by predominant-polarity yielded predictive associations, including the polarity of first episodes and risk of suicide attempts. Such subtyping may contribute to improve planning of clinical care and to biological studies of BPD.