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EDITORIALS: Yoav Ben-Shlomo and Kailash Bhatia Using monoamine oxidase type B inhibitors in Parkinson's disease BMJ 2004; 329: 581-582 [Full text]

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Safety issues with dopamine agonists

Marie-Helene Marion, Michael Schachter   (6 October 2004)

Safety issues with dopamine agonists 6 October 2004
Marie-Helene Marion, Consultant Neurologist and Hon Senior Lecturer St. George's Healthcare NHS Trust,Blackshaw Road,London,SW17 0QT, Michael Schachter Send response to journal: Re: Safety issues with dopamine agonists	Selegiline is not the only antiparkinsonian drug which has been the focus of controversy on grounds of safety in the last few years [1]. Dopamine agonists, in particular the dopamine agonists pergolide and bromocriptine [2], have been reported to be associated with valvulopathy. This had already been reported with long-term use of other ergot derivatives such as methysergide and with serotonergic anorectic drugs such as fenfluramine [3].Van Camp studied 78 parkinsonian patients taking pergolide and concluded that 33% of them had restrictive valvular changes on echocardiographic criteria:7% of the group stopped the drug because the valve disease led to symptoms. The fibrotic valvular changes seen with pergolide are consistent with the pericardial, pleural and retroperitoneal fibrosis reported previously with ergot derivatives [4]. A plausible mechanism for the fibrosis may be the activation of 5-HT2B receptors on interstitial fibroblasts in each organ [5]. Many issues are still to be addressed, in particular the true incidence of this side-effect, the risk factors, which appear to include the total degree of exposure to the drugs but are also likely to include pharmacogenomic considerations, and the potential reversibility of the lesions. However, it is important that clinicians are aware of this potential risk with dopaminergic ergot derivatives when considering therapeutic strategies in Parkinson's disease. 1. Ivens NJ, Stowe RL, Marro J et al. Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ 2004; 329: 593 2. van Camp G, Flamez A, Cosyns B et al. Treatment of Parknsons's disease with pergolide and relation to restrictive valvular heart disease. Lancet 2004; 363:1179-1183 3. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997;337: 581-588 4.Shaunak S, Wilkins A, Pilling JB, Dick DJ.Pericardial, retroperitoneal, and pleural fibrosis induced by pergolide. J Neurol Neurosurg Psychiatry 1999;66:79-81 5.Fitzgerald LW, Burn TC, Brown BS et al, Possible role of vascular serotonin 5-HT2B receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol 2000; 57: 75-81 Competing interests: Each author has given a talk at clinical meetings sponsored by GSK