Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study

Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States
Journal of Psychopharmacology (Impact Factor: 2.81). 07/2006; 20(4):536-46. DOI: 10.1177/0269881106059693
Source: PubMed

ABSTRACT This study compares the efficacy, safety, and tolerability of a partial dopamine agonist, aripiprazole, with placebo in the treatment of patients with bipolar I disorder experiencing an acute manic or mixed episode. In total, 272 hospitalized patients were randomized to aripiprazole 30 mg/day or placebo in this 3-week, double-blind, placebo-controlled trial. Dosing could be reduced to 15 mg/day for tolerability and, subsequently, increased to 30 mg/day based on clinical response. Primary efficacy measure was mean change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score; response was defined as > or = 50% decrease from baseline YMRS score. Aripiprazole-treated patients demonstrated significantly greater improvement from baseline to endpoint in mean YMRS total scores compared with placebo-treated patients as early as Day 4 and sustained through Week 3. A significantly higher response rate was observed in aripiprazole-treated patients (53% vs. 32% at endpoint). Aripiprazole produced significantly greater improvements from baseline on other efficacy assessments compared with placebo, including Clinical Global Impression - Bipolar Version Severity and Improvement scores. The 30 mg/day dose was maintained by 85% of aripiprazole-treated patients. Incidence of discontinuations due to adverse events was similar for aripiprazole (8.8%) and placebo (7.5%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight and was not associated with elevated serum prolactin or QTc prolongation. In conclusion, aripiprazole demonstrated superior efficacy to placebo in the treatment of patients with bipolar I disorder presenting with acute manic or mixed episodes, and exhibited a favourable safety and tolerability profile.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. We reviewed the treatment of bipolar mixed states using efficacy data of licensed and non-licensed physical or pharmacological treatments. Methods. We conducted a literature search to identify published studies reporting data on mixed states. Grading was done using an in-house level of evidence and we compared the efficacy with treatment recommendations of mixed states in current bipolar disorder guidelines. Results. A total of 133 studies reported data on mixed states, and seven guidelines differentiate the acute treatment of mixed states from pure states. The strongest evidence in treating co-occurring manic and depressive symptoms was for monotherapy with aripiprazole, asenapine, extended release carbamazepine, valproate, olanzapine, and ziprasidone. Aripiprazole was recommended in three guidelines, asenapine in one, and carbamazepine and ziprasidone in two. As adjunctive treatment, the strongest evidence of efficacy was for olanzapine plus lithium or valproate. For maintenance, there is evidence for the efficacy of monotherapy with valproate, olanzapine, and quetiapine. In the six guidelines valproate or olanzapine are first line monotherapy options; one recommends quetiapine. Recommended add-on treatments are lithium or valproate plus quetiapine. Conclusions. There is a lack of studies designed to address the efficacy of medications in mixed affective symptoms. Guidelines do not fully reflect the current evidences.
    The World Journal of Biological Psychiatry 05/2014; 15(5):1-14. DOI:10.3109/15622975.2014.908238 · 4.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Second-generation antipsychotics, approved for the treatment of mania, are associated with adverse effects such as weight gain and metabolic disorders. Aripiprazole, a recently introduced second-generation antipsychotic, are thought to account for its low propensity for weight gain, metabolic disturbances and sedation. The purpose of this study was to investigate the effect of risperidone versus aripiprazole in the treatment of acute mania. Fifty patients with acute episodes of mania were enrolled in this study, and they were randomly assigned into a risperidone group of 24 cases and an aripiprazole group of 26 cases. In group A, aripiprazole with a dose of 5-30 mg/day and in group B, risperidone with a dose of 2-8 mg/day was given to patients. The average dose of aripiprazole was 27 mg/day, and the average dose of risperidone was 6 mg/day. The effects of each drug for the treatment of acute mania were assessed on the 1(st) day of admission and on days 2, 4, 6, 8 and at weeks 2, 4 and 6 after therapy using the young mania rating scale (YMRS) and at the baseline and on weeks 3 and 6 after admission using the clinical global impression (CGI) scale. The mean age of the group of risperidone was 34 ± 8.6 years and in a group of aripiprazole it was 34 ± 9.1 years (P = 0.83). Comparison of YMRS scores over the period of 6 weeks revealed a statistically significant difference in both groups (P < 0.0001). There was also a statistically significant difference in YMRS scores between risperidone and aripiprazole at day 8 (P = 0.026) and weeks 2 (P = 0.035) and 4 (P = 0.042). There was also a statistically significant difference in CGI-Severity scale score at weeks 3 (P = 0.003) and 6 (P = 0.000) and in CGI-Improvement scale score at weeks 3 (P = 0.005) and 6 (P = 0.002). The most common side-effect observed in both groups was headache (0%15/4 in aripiprazole vs. %16/7 in risperidone). Aripiprazole that is readily available in our market, could be considered more effective than risperidone in the treatment of acute mania.
    Journal of research in medical sciences 08/2014; 19(8):733-738. · 0.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antipsychotics (AP) induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA) and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss). Duration of AP-use was stratified as follows: ≤6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.
    PLoS ONE 04/2014; 9(4):e94112. DOI:10.1371/journal.pone.0094112 · 3.53 Impact Factor