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Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials
Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials
Background:? Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking.

Objectives:? To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD.

Methods:? We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis.

Results:? Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53–0.86] for lithium, 0.68 (95% CI = 0.55–0.85) for lamotrigine, and 0.82 (95% CI = 0.57–1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49–0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35–0.79 and RR = 0.37; 95% CI = 0.24–0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46–0.91 and RR = 0.40; 95% CI = 0.20–0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34–0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12–2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08–3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31–3.70). There were few data for carbamazepine or medications given as adjunct therapy.

Conclusions:? Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment.

antipsychotics, bipolar disorder, maintenance, mood stabilizers, systematic review
1398-5647
394-412
Smith, Lesley A.
fe97f3af-7911-492e-85b8-b8a3444edb48
Cornelius, Victoria
b75c21d7-2c25-495c-9107-e39453a72bdd
Warnock, Adrian
50468626-a052-438a-8296-a86f848bb90f
Bell, Angus
8f7ae18b-efae-4302-bc59-5c31baf6f99a
Young, Allan H.
9f9548bb-7449-4a2a-a70a-3aad78d2c454
Smith, Lesley A.
fe97f3af-7911-492e-85b8-b8a3444edb48
Cornelius, Victoria
b75c21d7-2c25-495c-9107-e39453a72bdd
Warnock, Adrian
50468626-a052-438a-8296-a86f848bb90f
Bell, Angus
8f7ae18b-efae-4302-bc59-5c31baf6f99a
Young, Allan H.
9f9548bb-7449-4a2a-a70a-3aad78d2c454

Smith, Lesley A., Cornelius, Victoria, Warnock, Adrian, Bell, Angus and Young, Allan H. (2007) Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disorders, 9 (4), 394-412. (doi:10.1111/j.1399-5618.2007.00490.x).

Record type: Article

Abstract

Background:? Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking.

Objectives:? To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD.

Methods:? We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis.

Results:? Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53–0.86] for lithium, 0.68 (95% CI = 0.55–0.85) for lamotrigine, and 0.82 (95% CI = 0.57–1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49–0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35–0.79 and RR = 0.37; 95% CI = 0.24–0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46–0.91 and RR = 0.40; 95% CI = 0.20–0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34–0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12–2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08–3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31–3.70). There were few data for carbamazepine or medications given as adjunct therapy.

Conclusions:? Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment.

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More information

Published date: 1 June 2007
Keywords: antipsychotics, bipolar disorder, maintenance, mood stabilizers, systematic review

Identifiers

Local EPrints ID: 162295
URI: http://eprints.soton.ac.uk/id/eprint/162295
ISSN: 1398-5647
PURE UUID: 3e523f73-af1b-493a-a5a0-81a72d3988f7

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Date deposited: 18 Aug 2010 10:37
Last modified: 08 Jan 2022 08:38

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Contributors

Author: Lesley A. Smith
Author: Victoria Cornelius
Author: Adrian Warnock
Author: Angus Bell
Author: Allan H. Young

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