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Second-generation antipsychotics plus mood stabilizers best for mania
10 April 2007
Arch Gen Psychiatry 2007; 64: 442?455

Acute mania is best treated with second-generation antipsychotics combined with mood stabilizers, findings from a meta-analysis show.

"Recommendations of treatment guidelines concerning the use of second-generation antipsychotic agents for acute mania vary substantially across committees or working groups," note Harald Scherk (Georg-August University G?ttingen, Germany) and colleagues.

As previously reported in MedWire News, guidelines tend to recommend mood stabilizer monotherapy as first-line treatment for mania, but many clinicians use second-generation atypical antipsychotics in conjunction with mood stabilizers.

Scherk and team conducted a meta-analysis addressing the use of second-generation antipsychotics in the treatment of acute mania, compared with placebo, mood stabilizers and haloperidol, and when combined with mood stabilizers versus mood stabilizers alone.

They reviewed the medical literature for studies involving aripiprazole, amisulpride, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zotepine, and identified a total of 24 studies involving 6187 patients.

Overall, second-generation antipsychotics were significantly more effective in treating mania than placebo. For the second-generation antipsychotics combined, patients were 1.67 times more likely to respond to treatment, defined as at least a 50% decrease in Young Mania Rating Scale scores, than to placebo.

Dropout rates due to adverse events did not differ between treatment and placebo groups, but the risk of extrapyramidal symptoms (EPS) was greater with second-generation antipsychotics.

Second-generation antipsychotics also proved superior to mood-stabilizer drugs. The chance of patients responding to treatment was 1.15 times greater for second-generation antipsychotics than for mood stabilizers, but these treatments did not differ with regard to dropout rates and EPS.

Adding second-generation antipsychotics to mood stabilizers increased treatment efficacy compared with mood stabilizers alone. Patients taking combined treatment were 1.45 times more likely to respond than those taking mood stabilizer monotherapy.

Patients receiving combined treatment were also less likely to dropout of the study because of inefficacy was also less likely with combined treatment.

Second-generation antipsychotics did not prove superior to haloperidol for the treatment of acute mania. However, haloperidol-treated patients showed a higher dropout rate due to adverse events and higher rates of extrapyramidal symptoms.

The researchers note that "adverse effects might hamper the clinical effectiveness of an antipsychotic agent despite its efficacy." The main ones identified in the meta-analysis were weight gain, somnolence, and EPSs.

They add: "The second-generation antipsychotics are not alike, and this 'class' of drugs is heterogenous within itself."

Scherk et al. conclude in the Archives of General Psychiatry, "Combination treatment with a second-generation antipsychotic and mood stabilizer should be the treatment of choice, in particular for severe manic episodes."

Abstract

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