Selegiline-induced postural hypotension in Parkinson's disease: A longitudinal study on the effects of drug withdrawal

OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD ) randomized to receive 10 mg selegiline per day and L-dopa compared with t hose taking L-dopa alone. Recently, Lye found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension w hich was abolished by withdrawal of selegiline. This unwanted effect on pos tural blood pressure was not the result of underlying autonomic failure. Th e aims of this study were to confirm our previous findings in a separate co hort of patients and to determine the time course of the cardiovascular con sequences of stopping selegiline in the expectation that this might shed li ght on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were stu died repeatedly in PD patients receiving selegiline and as the drug was wit hdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was mar ked ill six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotens ion occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontin uation of the drug. Stopping selegiline also significantly reduced the supi ne systolic and diastolic blood pressures consistent with a previously unde scribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in com bination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamp hetamine are discussed.