Individuals who use methamphetamine or its metabolite amphetamine face a threefold increased risk of developing Parkinson's disease (PD) compared with nonusers, and the risk may be particularly high in women, new research shows.
The retrospective cohort study of Utah residents confirms an earlier report of increased PD risk among meth users, although that study was limited to California inpatients and did not report risks based on sex.
Lead author of the new study, Karen Curtin, PhD, University of Utah, Salt Lake City, and associate director, Utah Population Database (UPDB), called the findings "sobering."
"If you think about how many people worldwide get Parkinson's disease and the explosion over the last couple of decades in the use of methamphetamine and amphetamine-type stimulants in the drug-using population, these long-range effects could have significant consequences both for individuals and for the communities they live in."
There are also implications in terms of the healthcare burden, she added. "Parkinson’s disease is a long-term illness, and treatment is expensive and it gets progressively worse."
The study was published online December 11 in Drug and Alcohol Dependence.
Young Victims
Researchers used the UPDB, which houses computerized records for nearly 8 million people, as well as University of Utah Healthcare and Intermountain Healthcare (UUHC/IH) records. Therefore, they had access to inpatient discharge records, including admissions from an emergency department, as well as comprehensive outpatient clinic records from the largest healthcare providers of patient services in the state.
The primary outcome was time from baseline (January 1, 1996) to index diagnosis of PD or PD/Parkinsonism/essential tremor (PD/PT) to the end of 2011.
Those with HIV were excluded from the study because it can result in parkinsonismlike symptoms.
The study included these cohorts:
A meth/amph cohort, which included 4935 patients aged 30 years or older who were using this drug but no other illicit drugs, including cocaine, and who did not have any alcohol-use diagnoses
A cocaine cohort of 1867 patients aged 30 years or older who did not use meth/amph or other illicit drugs except cocaine or abuse alcohol
An unexposed, randomly selected age- and sex-matched (5:1) control group for each of the exposed groups, representative of the Utah population, who did not have a prior diagnosis of PD or PD/PT or an indication of illicit drug use or alcohol abuse
Results showed an approximate threefold significant increased PD risk based on the hazard ratio (HR) of methamphetamine/amphetamine users (men and women combined) compared with unexposed control individualss (HRPD 2.8, 95% confidence interval [CI] 1.6-4.8; P <10-3; HRPD/PT, 3.1, 95% CI 2.1-4.5; P < 10-4).
Dr Curtin noted that a diagnosis of PD was found in patients as young as late 30s and early 40s.
"Jenny Crank Diet"
An increased risk for PD/PT in women who were exposed to meth/amphetamines compared with female control individuals (HRPD/PT, 5.0; 95% CI, 2.9 - 8.6; P < 10-4) was larger than in men (HRPD/PT, 1.9; 95% CI; 1.1 - 3.5; P = .03), although confidence intervals overlap. A case-only comparison of female vs male meth/amph users was statistically nonsignificant.
"We need more research and more confirmation from other studies" to explain why this sex difference might exist, commented Dr Curtin.
Researchers wanted to investigate sex differences for a number of reasons. In 2012, 19% of patients who were admitted for drug dependence in Utah claimed meth as their principal drug of choice, and women were almost twice as likely as men to have a meth-related hospital admission (27% vs 15%).
"Women begin to use illicit drugs in lower doses than men, but they tend to more rapidly escalate to become addicted, and they seem to have greater risk for relapse," said Dr Curtin. "They also seem to have more comorbidities, like depressive disorder or psychological disorders."
During the past 10 years, there have been growing concerns about young women using meth, she said. "There's this perception that it will help them lose weight after pregnancy and have more energy; it was termed the Jenny Crank diet" (crank is slang for meth).
Utah is the 17th leading state in terms of meth use. At one time, meth was relatively cheap and was easy to make in home laboratories, although many of these have been shut down, said Dr Curtin.
Nearly half of the meth/amph-exposed individuals in the current study were women. By comparison, in the cocaine group, male users outnumbered female users by nearly 2 to 1.
Smoking's Role
The cocaine cohort had no increased risk for PD/PT compared with unexposed control individuals. Dr Curtin noted, however, that the number of outcomes was extremely limited in the exposed patients.
Although meth affects dopamine receptors in the brain, cocaine does not work through this pathway, said Dr Curtin. She added that including the cocaine cohort indicated that the increased risk for PD was not just through illicit drug use but specifically through meth use.
The researchers were interested in the potential confounder of cigarette smoking. Utah has a lower smoking rate than the rest of country, although meth addicts in general have very high smoking rates. At the same time, smoking has been consistently associated with decreased PD risk.
"Maybe that could be why women are at greater risk," Dr Curtin speculated. "They don't smoke as much as men and so may not have that protective effect. What's really chilling is that about 70% or 80% of meth users smoke in Utah ― and probably 90% nationwide ― so what would the risk estimates look like if these people were nonsmokers? Is the smoking keeping the risk from being even higher?"
In this study, adjusting for tobacco use did not substantially affect the estimated risk for PD/PT in the meth/amph vs cocaine cohorts.
Researchers did not adjust for race or ethnicity because 80% of Utah residents are non-Hispanic whites. However, PD prevalence differs between races as well as with regard to sex, with rates being higher among whites than nonwhites, said Dr Curtin.
The age at first use of meth averages about 18 years, whereas the average age at onset of PD is about 60 years. Asked whether PD not only occurs more often among meth addicts but also earlier, Dr Curtin said that her data suggest that this is the case.
"We have some indication that the time to the index diagnosis in the meth users was a shorter period than in controls."
The study findings underscore the importance of educating young people about the long-term consequences of using meth, said Dr Curtin. She pointed out that public health campaigns using descriptive images of people with lung cancer "have certainly kept young adults from starting to smoke."
A potential source of bias in the study was that the administrative claims data may not have correctly identified PD. As the authors noted, there is no "gold standard" diagnostic test for PD, and results of studies that evaluated the accuracy of the relevant diagnostic codes are mixed.
In addition, the authors assumed that index drug abuse preceded the first diagnosis of PD/PT, but it is possible that a diagnosis of the disease came before drug exposure. And they did not control for exposure to antipsychotic medications that may have side effects that mimic PD.
Next on Dr Curtin's research agenda is gathering more information about the impact of smoking on PD risks among drug users. She also plans to try to corroborate the PD diagnostic evidence by using data on levodopa and carbidopa, which are treatments that virtually all PD patients are prescribed at some point. In addition, more research is being planned using sex-specific models in the laboratory.
Mounting Evidence
Commenting on the study for Medscape Medical News, Michael S. Okun, MD, professor, University of Florida Center for Movement Disorders and Neurorestoration in Gainesville and national medical director, National Parkinson Foundation, said the study adds to the "mounting evidence" that supports the idea that illicit drugs can increase the risk of Parkinson’s disease.
"Though these data cannot be interpreted to mean that everyone who takes a recreational drug will get Parkinson's disease, it is important for users to be aware of this strong association," added Dr Okun, who is also author of Parkinson's Treatment: 10 Secrets to a Happier Life.
The authors and Dr Okun have reported no relevant financial relationships.
Drug Alcohol Depend. Published online Dec. 11, 2014. Abstract
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Cite this: Methamphetamine Use Triples Parkinson's Risk - Medscape - Dec 22, 2014.
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