Major new meta-analysis shows that antipsychotics are significantly more effective than mood stabilisers for treating acute mania

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Researchers from Oxford and Verona have published a major new meta-analysis in the Lancet, which measures the effectiveness of all anti-manic drugs.

The review team searched and found 68 randomised controlled trials from 1980-2010 (a total of 16,073 patients).  The study includes a range of antipsychotics and mood stabilisers used at a therapeutic dose range for the treatment of acute mania in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, quetiapine, risperidone, topiramate, and ziprasidone.

The researchers used an intention to treat analysis and measured the mean change in mania rating scales and patient drop-outs as the main outcomes.

The following drugs were significantly more effective than placebo:

  • Haloperidol ([standardised mean difference] -0·56 [95% confidence interval -0·69 to -0·43])
  • Risperidone (-0·50 [-0·63 to -0·38)
  • Olanzapine (-0·43 [-0·54 to -0·32]
  • Lithium (-0·37 [-0·63 to -0·11])
  • Quetiapine (-0·37 [-0·51 to -0·23])
  • Aripiprazole (-0·37 [-0·51 to -0·23])
  • Carbamazepine (-0·36 [-0·60 to -0·11]
  • Asenapine (-0·30 [-0·53 to -0·07])
  • Valproate (-0·20 [-0·37 to -0·04])
  • Ziprasidone (-0·20 [-0·37 to -0·03])

These drugs were no more effective than placebo:

  • Gabapentin
  • Lamotrigine
  • Topiramate

Overall, Haloperidol had the highest number of significant differences and was significantly more effective than:

  • Lithium (SMD -0·19 [95% CI -0·36 to -0·01])
  • Quetiapine (-0·19 [-0·37 to 0·01])
  • Aripiprazole (-0·19 [-0·36 to -0·02])
  • Carbamazepine (-0·20 [-0·36 to -0·01])
  • Asenapine (-0·26 [-0·52 to 0·01])
  • Valproate (-0·36 [-0·56 to -0·15])
  • Ziprasidone -0·36 [-0·56 to -0·15])
  • Lamotrigine (-0·48 [-0·77 to -0·19])
  • Topiramate (-0·63 [-0·84 to -0·43])
  • Gabapentin (-0·88 [-1·40 to -0·36])

Risperidone and olanzapine also did well in the results as they were shown to be more effective than valproate, ziprasidone, lamotrigine, topiramate, and gabapentin.

Drop-out rates are always important in this kind of study and the researchers found that olanzapine, risperidone, and quetiapine led to significantly fewer discontinuations than did lithium, lamotrigine, placebo, topiramate, and gabapentin.

The authors concluded:

Overall, antipsychotic drugs were significantly more effective than mood stabilisers. Risperidone, olanzapine, and haloperidol should be considered as among the best of the available options for the treatment of manic episodes. These results should be considered in the development of clinical practice guidelines.

Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet. 2011 Aug 16. [Epub ahead of print] [PubMed abstract]

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