Table 1

Optimal maintenance agents in bipolar disorder

Maintenance agentCBR*EBR†Utility
Mood stabiliser
 Lithium✓✓✓Level IClassic frontline option for bipolar, especially mania-dominant.3 12 31 Commonly used as adjunct with atypical antipsychotics. Requires close monitoring to maintain within therapeutic preventative levels. High risk of recurrence on abrupt cessation15
 Carbamazepine✓✓-–Less effective than lithium; may confer greater benefit in combination with lithium than either alone.[32] May also suit rapid-cyclers.[3] Not a first--line choice. High potential side-effect burden3
 Lamotrigine✓✓Level IIIMore effective for preventing depressive recurrence.12 Commonly used in combination with an antimanic prophylactic agent but may be suitable as monotherapy for depressive-dominant patients.33 May be appropriate for non-classic cases with mixed features or rapid cycling3
 Valproate✓✓Level IIIEvidence not yet robust34 but commonly used for maintenance.3 Recent review found some limited evidence of maintenance efficacy, as adjunct.14 Evidence suggests better adherence than for lithium.14 Strongly contraindicated in pregnancy12
Second-generation antipsychotics
 AripiprazoleLevel III as adjunctCurrently being longitudinally tested26 with previous research only supporting short-term benefit as monotherapy versus other agents.35 Reduces or prevents manic and mixed more so than depressive symptoms12 28
 ClozapineHigh side-effect risk. Best suited in treatment-resistant cases after other avenues exhausted
 Olanzapine✓✓Level IIISomewhat efficacious for preventing manic and mixed relapse with mixed evidence for efficacy in depression.25 High metabolic risk with long-term use. Few studies of sufficient duration to investigate long-term maintenance rather than continuation. Much evidence draws from enriched samples12
 Quetiapine✓✓Level IIIEfficacious for preventing manic and depressive relapse.23 36 Suitable for rapid cyclers in short term.37 Evidence of long-term maintenance efficacy as adjunct38
 Risperidone-LAILevel III as adjunctSome enriched design results show maintenance efficacy as adjunct.39 40 Suitable if poor adherence early in treatment history. Only potentially suitable as monotherapy in mania-dominant patients3
 ZiprasidoneLevel III as adjunctSome evidence suggesting suitable as adjunct for long-term mania prophylaxis41
  • *Consensus-based research derived from working group preparing Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guideline: Mood Disorders for ANZJP. (Malhi et al, 2014; under consideration from ANZJP). Checks indicate strength of available evidence for use—3 indicates strong, 2 moderate or 1 limited.

  • †Evidence-based research using NHMRC levels of evidence. I, systematic review of level II studies; II, randomised controlled trial; III, other study designs using controls; IV, case series with post-test or pretest/post-test outcomes.