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Bipolar disorder - Evidence
Evidence on anticonvulsants for treating acute mania

The National Institute for Health and Clinical Excellence (NICE) concluded, on the basis of limited evidence, that valproate is effective in the treatment of mania. NICE also found evidence that carbamazepine is more effective than placebo for treating mania and acute mania. There is no good evidence that other anticonvulsants are effective for treating mania [National Collaborating Centre for Mental Health, 2006].

Adults

NICE based their conclusions on six randomized controlled trials (RCTs).

  • Sodium valproate:
    • One placebo-controlled trial (n = 141) found evidence that valproate semisodium was more effective than placebo for treating mania.
    • A second RCT (n = 115) found evidence that valproate semisodium was as effective as olanzapine.
    • A third small RCT (n = 27) found evidence that valproate semisodium was less effective than lithium.
  • Carbamazepine:
    • NICE identified two RCTs (n = 443) that found evidence that carbamazepine was more effective than placebo for treating mania.
  • Gabapentin:
    • One RCT (n = 117) assessed the effectiveness of gabapentin with lithium or valproate. The results from this trial were inconclusive.

CKS identified several systematic reviews that have been published since the NICE guidance. Their results are consistent with NICE.

  • Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials [Smith et al, 2007a].
    • This review concluded that antipsychotics and mood stabilizers are significantly more effective than placebo for the treatment of acute mania. Their effect sizes were similar. Small differences between effect sizes may be due to differences in the populations included in the studies or to chance. Carbamazepine and lithium may be less well tolerated, and antipsychotics cause more extrapyramidal adverse effects.
  • Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs. monotherapy [Smith et al, 2007c].
    • This review concluded that the addition of antipsychotic treatment to established mood-stabilizer treatment is more effective than mood-stabilizer treatment alone.

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