Haloperidol reduces mania a little faster than second-generation antipsychotics, according to systematic review


There are a range of treatment options for people with bipolar disorder who are experiencing a manic episode. An important part of this treatment is to reduce the symptoms of mania and provide the individual with some level of normality.

I blogged this time last year about a meta-analysis in the Lancet that showed that antipsychotics were significantly more effective than mood stabilisers at treating acute mania.

It’s obviously helpful to reduce manic symptoms as quickly as possible, so this new meta-analysis and review from researchers in Barcelona will be welcomed by clinicians, as it provides a direct comparison as to the effectiveness of haloperidol (a first generation antipsychotic drug) with olanzapine, ziprasidone, aripiprazole, quetiapine and risperidone (second generation antipsychotics) in the first week of treatment.

The authors searched Medline and the Cochrane Central database for randomised controlled trials, including articles up to September 2011. They found 8 trials that met their inclusion criteria and rejected one trial because of poor methodological quality. The 7 trials that went into their meta-analysis included 2,037 patients.

Here’s what they found:

  • After 1 week, haloperidol was significantly more efficacious at reducing mania than:
    • Olanzapine (SMD: 0.40 [0.21, 0.59])
    • Ziprasidone (0.39 [0.18, 0.61])
  • Haloperidol had a non-significant superiority over:
    • Aripiprazole (SMD: 0.13 [-0.02, 0.19])
  • There were no significant differences between haloperidol and
    • Quetiapine (0.17 [-0.11, 0.44])
    • Risperidone (SMD: -0.10 [0.30, 0.09])

The authors concluded:

Haloperidol shows a faster onset of anti-manic action than second-generation antipsychotics. This difference may be related to D2 affinity. Haloperidol may be considered a treatment option in severely ill manic patients who require urgent relief of symptoms.

It’s worth noting that the effect sizes in this review are small, with the Standardised Mean Difference (SMD) being 0.17, with a 95% Confidence Interval ranging from 0.01 to 0.32.

Clearly, patients and clinicians will need to weigh up these effect sizes with the side effect profiles of the different treatments.


Goikolea JM, Colom F, Capapey J, Torres I, Valenti M, Grande I, Undurraga J, Vieta E. Faster onset of antimanic action with haloperidol compared to second-generation antipsychotics. A meta-analysis of randomized clinical trials in acute mania. Eur Neuropsychopharmacol. 2012 Jul 26. [Epub ahead of print] [PubMed abstract]

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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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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