0
1

Two randomized, double-blind, controlled studies have shown olanzapine monotherapy to be significantly better than placebo for the acute treatment of patients with mania or mixed episodes, with initial dosing of either 10 mg/day or 15 mg/day (9, 10). Somnolence, dry mouth, dizziness, and weight gain occurred significantly more frequently in the olanzapine group than in the placebo group. In another randomized, double-blind study, olanzapine was equivalent to haloperidol for patients with acute mania and was superior to haloperidol for patients whose index episode did not include psychotic features (11). Olanzapine monotherapy has also been compared with divalproex monotherapy in two randomized, double-blind, controlled studies. In one there was equivalent efficacy (12), and in the other olanzapine had superior efficacy (13). However, the side-effect profile for divalproex was more benign.

Olanzapine has also been studied as an adjunctive agent to traditional mood stabilizers. In a double-blind, randomized, controlled trial, olanzapine added to divalproex or lithium was superior to divalproex or lithium alone in patients who had had an inadequate response to at least 2 weeks of lithium or valproate monotherapy (14). Side effects included somnolence, hyperkinesia, and nausea.

The efficacy of risperidone monotherapy for the acute treatment of mania has been demonstrated in three randomized, double-blind, placebo-controlled trials. Risperidone monotherapy was superior to placebo in all three studies. In the three studies patients were started on 3 mg/day of risperidone, with titration to a maximum of 6 mg/day. Onset of action in one study was seen at day 3 (15), and in another at 1 week (16). In the third study, risperidone was equivalent to haloperidol and superior to placebo (17). Side effects included somnolence, hyperkinesia, and nausea.

Two randomized, double-blind, placebo-controlled studies examined the adjunctive use of risperidone with traditional mood stabilizers (i.e., lithium or divalproex) (18, 19). In both studies the combination of risperidone with mood stabilizer outperformed mood stabilizer alone. The addition of risperidone substantially increased the prevalence of extrapyramidal symptoms.

The efficacy of ziprasidone as monotherapy in the acute treatment of patients with manic or mixed episodes was tested in two randomized, double-blind, placebo-controlled studies, with initial dosing of 40 mg twice a day (20, 21). Ziprasidone had an onset of action at day 2 in both trials and was superior to placebo at endpoint. The mean dosage in the two studies was 130 mg/day and 112 mg/day, respectively. Side effects included somnolence, dizziness, extrapyramidal syndrome, nausea, akathisia, and tremor.

Two studies of aripiprazole monotherapy in the acute treatment of mania have been published (22, 23). In a randomized, double-blind, controlled study, aripiprazole at a starting dosage of 30 mg/day was compared with placebo in patients with manic or mixed episodes (22). Aripiprazole was superior to placebo in efficacy, beginning at day 4. Side effects included nausea, dyspepsia, somnolence, vomiting, insomnia, and akathisia. A second study compared aripiprazole and haloperidol over 12 weeks (23). The drugs performed similarly regarding improvement in manic symptoms, but substantially more aripiprazole patients completed the study. Extrapyramidal symptoms were much higher for haloperidol.

The efficacy of quetiapine in patients with manic episodes has been studied in two different 12-week randomized, double-blind, placebo-controlled trials—one against lithium and the other against haloperidol (24, 25). Quetiapine was initiated at 100 mg on day 1, with an upward titration to 800 mg/day or higher. Quetiapine was equivalent in efficacy to the two active comparators, and both were superior to placebo at day 21. Side effects included dry mouth, somnolence, weight gain, and dizziness.

In another study, adjunctive quetiapine or placebo was given to acutely manic patients who were still manic after at least 7 days of treatment with lithium or divalproex. Quetiapine was initiated at 100 mg and titrated to 400 mg/day by day 4, with a target dose of 200–800 mg/day (26). The quetiapine treatment group had a significantly higher response rate and reduction in manic symptoms. The mean last-week dosage in all patients receiving quetiapine was 504 mg/day.

There have been two recently published randomized, double-blind, placebo-controlled studies of the extended-release formulation of the anticonvulsant carbamazepine for the acute treatment of manic or mixed episodes (27, 28). In both studies, carbamazepine extended-release was initiated at 400 mg in divided doses on day 1 and increased as tolerated up to 1,600 mg/day. The mean final dosages were 756 mg/day (27) and 643 mg/day (28), respectively. An onset of action was seen at day 14 in the first trial and at day 7 in the second trial, and both trials found carbamazepine extended-release to be superior to placebo at endpoint. Side effects included dizziness, somnolence, nausea, vomiting, ataxia, blurred vision, dyspepsia, dry mouth, pruritus, and speech disorder.

The many monotherapy and adjunctive therapy studies of mania since 2002 provide a number of new options for clinicians in the acute treatment of patients with mania.

A significant clinical concern is metabolic effects associated with second-generation antipsychotics (29). Clozapine and olanzapine are associated with increased risks of developing diabetes mellitus and dyslipidemia. A recent comparative antipsychotic trial in schizophrenia suggested significantly greater weight gain for olanzapine than for the other antipsychotics studied (i.e., perphenazine, quetiapine, risperidone, and ziprasidone) (30). Clozapine and olanzapine are associated with the most weight gain, risperidone and quetiapine with moderate weight gain, and ziprasidone and aripiprazole with minimal weight change. Because of these risks, clinicians have been advised to monitor weight, waist circumference, blood pressure, glucose, and lipids at baseline and at monthly intervals in patients on these medications (31).

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Helping Parents, Youth, and Teachers Understand Medications for Behavioral and Emotional Problems: A Resource Book of Medication Information Handouts, 3rd Edition > Chapter 3.  >
Helping Parents, Youth, and Teachers Understand Medications for Behavioral and Emotional Problems: A Resource Book of Medication Information Handouts, 3rd Edition > Chapter 9.  >
Helping Parents, Youth, and Teachers Understand Medications for Behavioral and Emotional Problems: A Resource Book of Medication Information Handouts, 3rd Edition > Chapter 15.  >
Psychiatric News
Read more at Psychiatric News >>
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation