An Article published by The Lancet shows that antipsychotic drugs are much more effective than mood stabilisers in tackling acute manic episodes. The researchers also ranked antipsychotic drugs according to their effectiveness, and showed that three—haloperidol, risperidone, and olanzapine—outperformed other drugs. Since current guidelines do not differentiate between the drugs, these data could offer useful clinical guidance, say Andrea Cipriani, Section of Psychiatry and Clinical Psychology, University of Verona, Italy, and John Geddes, Professor of Epidemiological Psychiatry at University of Oxford, UK, who coordinated the research project.
Mania, defined as an "excessively raised mood" affects about 1% of the population; it tends to alternate with depression, and defines the diagnosis of bipolar disorder. Cipriani and colleagues collectively analysed the results from 68 randomised controlled trials (16 073 participants) from Jan 1, 1980, to Nov 25, 2010, which compared the most common drugs used to treat acute mania in adults. They found that haloperidol, olanzapine, and risperidone were the most effective antimanic drugs, and haloperidol had the highest number of significant differences in head-to-head comparisons, being better than aripiprazole, asenapine, carbamazepine, valproate, gabapentin, lamotrigine, lithium, quetiapine, topiramate, and ziprasidone, say the authors. Risperidone, olanzapine, and quetiapine were least likely to result in treatment discontinuation and were better than many mood stabilisers, such as lithium, lamotrigine, topiramate, and gabapentin.
The authors say: "These results have potential clinical implications that should be considered in the development of clinical practice guidelines. Strikingly, some antipsychotic drugs were, overall, significantly more effective than mood stabilisers." Yet they caution: "All statements comparing the merits of one medicine with another must be tempered by the potential biases and uncertainties that result from choice of dose and choice of patients."
They conclude that their results: "emphasise the need for new treatments to show either greater efficacy or acceptability than the existing best standard treatments and serve as a disincentive to the development of drugs that offer little to patients other than increased costs."
In a linked Comment, Michael Berk at the School of Medicine, Deakin University, Geelong, Victoria, Australia and Gin S Malhi at the CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Sydney, NSW, Australia, say: "Haloperidol seems to have won the race for pole position in the treatment of acute mania. However, the management of manic episodes, or indeed acute therapy per se, is not the overriding therapeutic imperative in this polyphasic and capricious disorder. Instead, the main goals of treatment are attention to long-term mood stability and prophylaxis. The promotion of haloperidol as a first-line drug for acute mania is problematic in this context, since it lacks maintenance efficacy for depression—the predominant clinical state—and indeed carries an inherent risk of incident depression."
They conclude: "These findings are likely to attract much interest and have a substantial effect both on clinical practice guidelines and real world treatment, making it all the more crucial that the true comparative effectiveness and acceptability of antimanic drugs, and their positioning in broader management is understood".
Dr Andrea Cipriani, Section of Psychiatry and Clinical Psychology, University of Verona, Italy. T) +39 333 3046378 E) andrea.cipriani@univr.it
Dr Michael Berk, School of Medicine, Deakin University, Geelong, VIC, Australia. E) mikebe@barwonhealth.org.au
Journal
The Lancet