Amphetamine Use Linked to Increased Parkinson's Risk

Kate Johnson

February 25, 2011

February 25, 2011 — Exposure to the amphetamines Benzedrine (Amedra Pharmaceuticals) and Dexedrine (GlaxoSmithKline) is associated with a roughly 60% boost in the risk of developing Parkinson’s disease (PD), a new study suggests.

The preliminary findings were released February 20 and will be presented in April at the American Academy of Neurology's 63rd Annual Meeting in Honolulu, Hawaii.

The results could have important clinical implications if they are confirmed by other studies, said principal investigator Stephen K. Van Den Eeden, PhD, a research scientist with Kaiser Permanente Northern California in Oakland.

Amphetamines are prescribed for the treatment of attention-deficit/hyperactivity disorder, narcolepsy, and traumatic brain injuries, and there is also growing interest in their use as cognitive enhancers.

"If this is a true association and someone has a family history of Parkinson's disease, that would weigh in a clinical decision," Dr. Van Den Eeden told Medscape Medical News.

"In prescribing amphetamines we need to weigh the benefits and risks, and [PD family history] could be one risk to consider, though small, as the absolute risk does not appear to be large at this point."

Amphetamine Exposure

The study involved 66,438 people who participated in the Multiphasic Health Checkup Cohort Exam between 1964 and 1973 and were followed for a mean of 38.8 years. The mean age of the participants at baseline was 36 years, and none of them had PD at that time; however, family history of the disease was not recorded.

By the end of the study, a total of 1154 participants had been diagnosed with PD, most of them at approximately 70 years of age.

All cases were diagnosed by a neurologist and identified by a review of electronic clinical records.

Amphetamine exposure was determined by 2 questions: 1 about the use Benzedrine or Dexedrine, and 1 about the use of weight-loss drugs. At the time of the study, amphetamines were commonly used for weight loss.

Cox proportional hazards models showed that participants with PD were much more likely to have been exposed to amphetamines than were participants who were free of the disease.

Compared with participants who had no exposure to amphetamines, those who reported using Benzedrine or Dexedrine "often" had an increased risk of developing PD (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.01 - 2.40). The effect was similar in women (HR, 1.55) and men (HR, 1.60).

In contrast, individuals who reported taking weight-loss medication did not have an increased risk (HR, 0.95; 95% CI, 0.75 - 1.21).

The reasons for no increased risk among those exposed to weight-loss medication deserve further study, said Dr. Van Den Eeden.

"We are looking into this a bit further as we speak to see if the association varied by other factors," such as obesity, or age, he said.

"The most obvious reason would likely be that the weight-loss question was about any drug for weight loss, some of which was certainly amphetamines, but other drugs were used at this time," he speculated. "In other words, the question was less specific and the participants likely responded thinking about a wide range of drugs, some of which may have been over-the-counter drugs."

Amphetamines affect the release and uptake of dopamine, which is the key neurotransmitter involved in PD, he said.

Novel Association

The preliminary findings suggest a "novel association," although further prospective research is needed to confirm the results, said Anna Hohler, MD, assistant professor of neurology at Boston University Medical College, when reached for comment on the study.

"I will alert my patients about this preliminary finding when counseling them about these medications," Dr. Hohler added.

She said in addition to a family history of PD, other factors that might contribute to increased risk when combined with amphetamines include a history of head trauma and exposure to heavy metals or pesticides.

The study was supported by Kaiser Permanente Northern California. Dr. Van Den Eeden and Dr. Hohler have disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 63rd Annual Meeting. Released February 20, 2011, ahead of presentation.

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