Quetiapine or haloperidol as monotherapy for bipolar mania - a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial
ABSTRACT Patients (n=302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score.
YMRS score improved with quetiapine at Day 21 (-12.29 versus -8.32 for placebo; P<0.01). The difference in favor of quetiapine increased by Day 84 (-17.52 versus -9.48; P<0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P<0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day.
Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.
- SourceAvailable from: Jorge M Tamayo
- [Show abstract] [Hide abstract]
ABSTRACT: 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.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2012; DOI:10.1016/j.euroneuro.2012.05.017 · 5.40 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse events (AEs), lack of efficacy, or discontinuation due to any cause, and the number needed to treat or harm (NNT or NNH) were calculated for each medication individually and for all evaluable trials combined. The authors included 31 RCTs in the analyses comparing a MDR with placebo or with active treatment for acute mania, and 9 RCTs comparing a MDR with placebo or with active treatment for bipolar depression. According to the collected evidence, most of the MDRs when compared to placebo showed significant response and remission rates in acute mania. In the case of bipolar depression only quetiapine and, to a lesser extent, olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low discontinuation rates due to any cause or AE, although AE profiles differed among treatments. We concluded that most MDRs were efficacious and safe in the treatment of manic episodes, but very few MDRs have demonstrated being efficacious for bipolar depressive episodes.The International Journal of Neuropsychopharmacology 07/2010; 13(6):813-32. DOI:10.1017/S1461145709991246 · 5.26 Impact Factor