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Risperidone versus placebo in treatment of acute mania
- Charles N Antwi (21 December 2005)
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Competing Interests
- Gavin Mckay, Kalypso Markopoulou, Senior House Officer (21 December 2005)
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Charles N Antwi, Senior House Officer, Psychiatry none
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chantwi{at}fsmail.net Charles N Antwi
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Dear Sir, I read with great interest “Risperidone in the treatment of acute mania: Double-blind, placebo-controlled study” presented by Khanna et al. The paper is very relevant and findings are significant though it has some limitations. I believe the generalisability of the study results should be viewed with caution. As the study was conducted in India, it is probable that there was lack of multi-ethnicity among the study participants. The authors are not explicit about the concealment of allocation during randomisation. The absence of this aspect of methodology could lead to bias. In the study design, the authors randomised acutely manic patients to receive Risperidone or placebo. Acute mania is life threatening, it has a great impact on families and carers and is associated with significant suicide risk. Given the risk posed to the placebo group, I wonder if ethical approval was obtained, as this is not explicit in the article. However, the authors claim the study was conducted according to the Recommendations Guiding Physicians in Biomedical Research Involving Human Subjects, in the 1989 version of the Declaration of Helsinki (World Medical Association, 1989). Declaration of interest: none |
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Gavin Mckay, Specialist Registrar York Clinic, Guy's Hospital, 47 Weston street, London SE1 3RR. fax 02071883840 tel 02071887003, Kalypso Markopoulou, Senior House Officer
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Gavin.mckay{at}slam.nhs.uk Gavin Mckay, et al.
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Sirs, When reading Khanna et al’s well designed trial of risperidone in mania we could not help wonder about the ethical issues involved allowing treatment with placebo albeit with availability of additional benzodiazepine in severe mania. There is no mention of ethics committee approval of the study but the authors do say that it was conducted according to guidance issued by the World Medical Association (1989). However this guidance states, ‘The potential benefits, hazards and discomfort of a new method should be weighed against the advantages of the best current diagnostic and therapeutic methods’. A non-inferiority trial design against an accepted treatment e.g. haloperidol could have been adopted. Indeed this has been done by another company sponsored trial; there was no difference in outcome between risperidone and haloperidol. In terms of side effects haloperidol caused more extrapyramidal side effects and risperidone more hyperprolactaemia, (Smulevich et al, 2005). In the same issue of The Journal there was another company’s mania trial, this time a non-inferiority trial design was used to compare aripiprazole with haloperidol (Vieta et al 2005). Again however there was an ethical issue not discussed; the study protocol prohibited the use of anticholinergics because of ‘their potential to mask differences in treatment tolerability’. Indeed this was proved correct with a massive 49% of the haloperidol group discontinuing the treatment because of an adverse event. This does not affect the generalisability of the trial results as stated, rather it compromises its validity. In a time of increasing suspicion of pharmaceutical companies by clinicians e.g. Whitington et al (2004) their research should be conducted in a manner that is above reproach. Doing otherwise will only further irritate clinicians and consequently deny patients the likely benefits of novel treatments. Declaration of Interests The authors have accepted hospitality from Janssen-Cilag and Bristol-Myers Squibb. References Khanna, S., Vieta, E., Lyons, B., Grossman, F., Eerdekens, M., Kramer, M . (2005). Risperidone in the treatment of acute mania: Double- blind, placebo-controlled study British Journal of Psychiatry, 187, 229-234. Smulevich , AB., Khanna, S., Eerdekens, M., Karcher, K., Kramer, M., Grossman, F.(2005) .Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol European Neuropsychopharmacology.15(1),75-84. Vieta, E., Bourin, M., Sanchez, R., Marcus, R., Stock, E., McQuade, R., Carson, W., Abou-Gharbia, N., Swanink, R., Iwamoto, T., on behalf of the Aripiprazole Study Group(2005), Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: Double-blind, randomised, comparative 12-week trial . British Journal of Psychiatry 187, 235-242. Whittington , CJ., Kendall, T., Fonagy, P., Cottrell , D., Cotgrove, A., Boddington, E.(2004)Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet.363 (9418),1341-5. World Medical Association (1989) World Medical Association Declaration of Helsinki: Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects. http://www.fda.gov/oc/health/helsinki89.html. |
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