Authors' objectives:

To evaluate the clinical and cost-effectiveness of quetiapine, olanzapine and valproate semisodium in the treatment of mania associated with bipolar disorder.

Authors' results and conclusions: Treatments versus placebo: - Quetiapine appears superior to placebo in reducing manic symptoms, but is associated with side-effects such as somnolence, dry mouth and dizziness. - Olanzapine appears superior to placebo in reducing manic symptoms, but is also associated with side-effects such as somnolence, dry mouth and dizziness - Valproate semisodium appears superior to placebo in reducing manic symptoms, but may cause gastrointestinal side-effects. Treatments versus lithium: - There appears to be little difference between quetiapine and lithium in terms of effectiveness, but quetiapine is associated with somnolence and weight gain, whereas lithium is associated with tremor. - There appears to be little difference between olanzapine and lithium in terms of clinical effectiveness and adverse events. - There appears to be little difference between valproate semisodium and lithium in terms of clinical effectiveness and adverse events. Treatments as adjunct to mood stabilisers: - Quetiapine as adjunct therapy to mood stabilizers may be more effective than placebo in reducing mania and improving global health but it is associated with more dry mouth, somnolence, postural hypotension and asthenia. - Olanzapine as adjunct therapy to mood stabilisers may be more effective than placebo in reducing mania and improving global health, but it is associated with more dry mouth, somnolence, weight gain, increased appetite, tremor and speech disorder. Treatments versus haloperidol: - There was little difference between quetiapine and haloperidol in reducing mania, but haloperidol was associated with more extrapyramidal side-effects, such as akathisia and tremor. - There was little difference between olanzapine and haloperidol in terms of clinical effectiveness, but haloperidol was associated with more negative implications for health-related quality of life. - Valproate semisodium was as effective as haloperidol in a small, short-term trial of patients with psychotic features, but haloperidol caused more extrapyramidal side-effects. Treatments versus other comparators: - Intramuscular olanzapine and lorazepam were equally effective and safe in one very short (24 hour) trial. - Valproate semisodium and carbamazepine were equally effective and safe in one small trial in children. Head-to-head comparison: - Olanzapine may be more effective than valproate semisodium in reducing mania, but was associated with more dry mouth, increased appetite, oedema, somnolence, speech disorder, Parkinson-like symptoms and weight gain. - Valproate semisodium was associated with more nausea than olanzapine.

Authors' recommendations: Clinical effectiveness: In comparison with placebo, quetiapine, olanzapine and valproate semisodium appear superior in reducing manic symptoms, but all drugs are associated with adverse events. In comparison with lithium, no significant differences were found for olanzapine, quetiapine and valproate semisodium in terms of effectiveness. All drugs were associated with adverse events. Cost-effectiveness: Several limitations of the cost-effectiveness analysis exist, which inevitably means that the results should be treated with some caution. These include: (i) the possible bias introduced by using indirect evidence; (ii) the limited timeframe of the analysis and the exclusion of the costs and quality of life impact of adverse events; (iii) the exclusion of olanzapine and quetiapine combination therapies from the base-case models; (iv) the lack of data concerning the effectiveness of the drugs when used in second- and third-line treatments; and (iv) the lack of suitable data on quality of life. The available evidence derives from trials that are too small, methodologically flawed and rely on proxy data, that is, the use of the LOCF method for large proportions of patients. These limitations need to be carefully considered when interpreting the effectiveness evidence, and conclusions drawn from these data need to be treated with great caution.

Authors' methods: Systematic review, Economic evaluation

Project Status: Completed

URL for project: http://www.hta.ac.uk/1331

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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