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Are Antihypertensive Drugs Neuroprotective in Parkinson Disease?
A large case-control study suggests that calcium channel blockers are the only antihypertensives that reduce the risk for Parkinson disease.


For the past decade, the potential of antihypertensive agents to affect the incidence of Parkinson disease (PD) has been evaluated by various methodologies, yielding a confusing array of conclusions. Now, researchers have conducted a careful case-control study of incident PD diagnosis and its association with various antihypertensives. They identified 3637 patients with incident PD and 3637 well-matched controls from the U.K.-based General Practice Research Database, which contained at least 3 years of data before the index (diagnosis) date for each participant. The authors separately analyzed four major classes of antihypertensive drugs: angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II antagonists, and beta-blockers.

Use of calcium channel blockers — but not of the other antihypertensive classes — was associated with a significantly reduced risk for PD (odds ratio, 0.77). Risk reductions with this drug class were even greater with prolonged use and in people aged 80 or older. Use of beta-blockers for reasons other than cardiovascular disease or hypertension was associated with increased PD incidence. The authors attribute this association to the presence of symptoms such as tremor that often prompted the beta-blocker use and may have been parkinsonian manifestations.

Comment: The scope of this study, including its size and the number of classes of antihypertensive agents separately evaluated, clearly surpasses past attempts to assess the putative neuroprotective properties of these drugs, and in that respect brings us a step closer to a meaningful conclusion. The inherent uncertainties associated with the case-control method notwithstanding, this study deserves notice because of its great scientific rigor.

Although the authors do not discuss in any detail the mechanisms by which calcium channel blockers might be beneficial in Parkinson disease, the importance of calcium ions in various major neuronal functions supports a role in altering the natural history of this disorder. Aging and disease-related stressors (e.g., accumulation of reactive oxygen species or of disease-related proteins such as alpha-synuclein) can impair calcium homeostasis, thereby disrupting neuronal functions and accelerating the appearance of parkinsonian symptoms. A recent animal study demonstrated that increased reliance on calcium and increased susceptibility to stressors in aged dopaminergic neurons could be reversed by calcium channel blockers, allowing cells to use a healthier form of cellular homeostasis more typical of juvenile cells. Do these data suggest that calcium channel blockers could emerge as a neuroprotective therapy for PD? Relevant clinical research is being planned, so the answer to this important question may be only a few years away.

— Robert L. Rodnitzky, MD

Dr. Rodnitzky is Professor and Head, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City.

Published in Journal Watch Neurology April 15, 2008