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Risperidone in the treatment of acute mania: Double-blind, placebo-controlled study

  • Sumant Khanna (a1), Eduard Vieta (a2), Benjamin Lyons (a3), Fred Grossman (a3), Mariëlle Eerdekens (a4) and Michelle Kramer (a3)...

Abstract

Background

Severe mania is life-threatening, carries an increased risk of suicide and has a serious impact on patients and their families. Efficient and rapid control of episodes of acute mania is needed.

Aims

To evaluate the safety and efficacy of risperidone monotherapy for acute mania.

Method

In a 3-week, randomised, double-blind trial, 290 in-patients with bipolar l disorder with current manic or mixed episode and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexible doses of risperidone (1–6 mg per day) or placebo.

Results

Risperidone was received by 146 patients and placebo by 144. Their mean baselineYMRS score was 37. 2 (s. e. =0. 5). Significantly greater improvements were observed with risperidone than with placebo at weeks l and 2 and at end-point (total YMRS: P<0. 01). Extrapyramidal symptoms were the most frequently reported adverse events in the risperidone group.

Conclusions

In patients with severe manic symptoms, risperidone produced significant improvements in YMRS scores as early as week 1 and substantial changes at end-point. Treatment was well tolerated.

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Copyright

Corresponding author

Dr Sumant Khanna, The Psychiatric Clinic, 63 Paschmi Marg, Vasant Vihar, New Delhi, India. E-mail: sumantk_2002@yahoo.co.in

Footnotes

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Declaration of interest

B. L., F. G., M. E. and M. K. are employees of Johnson & Johnson Pharmaceutical Research and Development, which supported this study.

Footnotes

References

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Risperidone in the treatment of acute mania: Double-blind, placebo-controlled study

  • Sumant Khanna (a1), Eduard Vieta (a2), Benjamin Lyons (a3), Fred Grossman (a3), Mariëlle Eerdekens (a4) and Michelle Kramer (a3)...
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eLetters

Competing Interests

Gavin Mckay, Specialist Registrar
21 December 2005

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 thebest 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. Interms 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 adverseevent. 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 conductedin 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 InterestsThe authors have accepted hospitality from Janssen-Cilag and Bristol-MyersSquibb.

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 studyBritish 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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Conflict of interest: None Declared

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Risperidone versus placebo in treatment of acute mania

Charles N Antwi, Senior House Officer, Psychiatry
21 December 2005

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 hassome 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 leadto bias.

In the study design, the authors randomised acutely manic patients toreceive 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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Conflict of interest: None Declared

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