Rapid acting anti manic agents? Eur Neuropsychopharmacol. 2013 Apr


Individuals with acute mania require treatments that controls the symptoms promptly to avoid the many consequences of the disorder.Many medications are efficacious in treating mania,and most of these trials have assessed the outcome in 3-4 weeks time.Less is known about  the speed of the onset of action of these treatments. Fast improvement is desirable given the dangerous consequences.It has been suggetsed that  Haloperidol has antimanic properties and a faster onset of antimanic action compared to atypical antipsychotics.

Cipriani’s 2011 metaanalysis showed Haloperidol as one of the most efficacious antimanic drugs (superiority over aripiprazole, asenapine, quetiapine, and ziprasidone, and no differences with risperidone and olanzapine, among atypical antipsychotics). Atypicals are first line agents for mania in many guidelines. Side effect profiles have shifted the preference in favour of atypicals. There is also concern that haloperidol may not protect against switch to depression. Inspite of these factors, speed of action may become an important issue of consideration while treating manic episodes.

 J.M. Goikolea, F. Colom, J. Capapey, I. Torres, M. Valenti, I. Grande, J. Undurraga, E. Viet  from Barcelona bipolar disorders  program assessed the differences between haloperidol and second generation antipsychotics in terms of onset of antimanic action. 8 studies met the inclusion criteria, one was later excluded due to poor quality.5 second-generation antipsychotics (Aripiprazole  ,Olanzapine ,Risperidone ,Ziprasidone  ,Quetiapine) had been compared with haloperidol under the specified conditions. Mania scale score reduction at week 1 was the outcome of interest.


There is a modest but significant superiority of haloperidol over second generation antipsychotics ( as a group)  in the short-term (ie week 1) .The Standardized Mean Difference (SMD) was 0.17, with a 95% Confidence Interval ranging from 0.01 to 0.32. Haloperidol was significantly more efficacious than Olanzapine  and Ziprasidone  at week 1. A non-significant trend towards superiority of haloperidol was found over Aripiprazole.

There were no significant differences between Haloperidol and Quetiapine at one week in the one study included in this metaanalysis. However, at week 3 Haloperidol was more effective in this trial. Also, the dose of Haloperidol used  was low.Other trials have indicated milder antimanic action for Quetiapine.

There was no significant difference between haloperidol and risperidone. Risperidone, like haloperidol, have high D2 antagonism and it has also been shown in other trials as a potent mantimanic agent.

One has to consider the fact that patients participating in mania trials are usually not severely unwell.Clinicians often indicate that in severe cases haloperidol is often used.

Conclusions: Haloperidol have a faster onset of action in mania. A faster onset of action  do not imply that it is the first line agent. Selection of medication in acute mania should consider long-term factors as well. ( risk of switch to depression, the onset of a long-term prophylactic treatment, the predominant polarity, and also the long- term tolerability).

Summary of the article:

Faster onset of antimanic action with haloperidol compared to second-generation antipsychotics. A meta-analysis of randomized clinical trials in acute mania. Goikolea JM, Colom F, Capapey J, Torres I, Valenti M, Grande I, Undurraga J, Vieta E. Eur Neuropsychopharmacol. 2013 Apr;23(4):305-16



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