Naltrexone for Impulse Control Disorders in Parkinson's?

Megan Brooks

August 08, 2014

The opioid antagonist naltrexone may curb impulse control disorders (ICDs) in patients with Parkinson's disease (PD), preliminary research suggests.

Results from a pilot study conducted by investigators at the University of Pennsylvania, Philadelphia, showed that while the drug was not effective for the treatment of ICDs using a global assessment of response, it appeared to improve symptoms when measured by a PD-specific rating scale.

"The results of this preliminary study support further research with naltrexone (including at higher doses) or other opioid antagonists (e.g., nalmefene) for the treatment of ICDs in PD," the investigators, led by Daniel Weintraub, MD, write.

The study was published online July 17 in Neurology.

Tough to Manage

ICDs, such as compulsive gambling, buying, sexual behavior, and eating, are relatively common in patients with PD, particularly in association with dopamine agonist treatment, and can be tough to manage.

If symptoms are not severe, ICDs are currently managed by doing nothing. Other approaches include modification of current treatment, changing to another dopamine agonist, adding psychiatric medications (such as an antipsychotic or antidepressant), or considering deep-brain stimulation, said Dr. Weintraub.

Used to treat alcohol dependence, naltrexone has been shown to be effective in treating pathologic gambling in the general population in a controlled trial, and case reports suggest it may be efficacious in reducing ICDs in patients with PD receiving dopamine agonists.

The investigators tested the efficacy of naltrexone against placebo in 50 patients with idiopathic PD who developed ICD symptoms after the onset of PD and start of dopamine agonist treatment (ropinirole or pramipexole). The naltrexone group consisted of 26 patients and the placebo group consisted of 24 patients.

For the first 4 weeks of the trial, naltrexone was dosed at 50 mg daily. In case of nonresponse at 4 weeks, defined as a score of 1 or 2 on the Clinical Global Impression-Change (CGI-C) scale, the dose of naltrexone was increased to 100 mg daily for the final 4 weeks.

A total of 45 patients (90%) completed the study, and the results were mixed.

On the primary outcome, the clinician-based rating of global improvement (CGI-C), naltrexone did not demonstrate a significant benefit over placebo. For study completers, the CGI-C response rate was 54.5% in the naltrexone group and 34.8% in the placebo group (Fisher exact test, P = .23). The response rate difference favoring naltrexone was 19.8% (95% confidence interval [CI], –8.7% to 44.2%; odds ratio [OR], 1.6).

However, the researchers note that the study "lacked the statistical precision to exclude an important difference in response rates between naltrexone and placebo."

On the patient-completed, PD-specific ICD assessment — the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) — naltrexone treatment led to a significantly greater decrease in QUIP-RS score over time compared with placebo (P = .04).

The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI, 9.9 - 19.9) for naltrexone vs 7.5 points (95% CI, 2.5 - 12.6) for placebo.

Naltrexone was well tolerated in this patient population, with adverse events consistent with those seen in patients with alcoholism. The most common adverse effects were nausea (9.8%) and headache (6.6%).

Further Study Worthwhile

"One possible explanation for the discrepancy in the findings on the 2 outcome measures is that it is easier to detect a significant difference on a rating scale (continuous measure) compared with a global rating (dichotomous outcome) because the continuous measure contains more information and provides better power," the authors write.

Dr. Weintraub believes further study of naltrexone for ICDs in PD is worthwhile.

"I think the fact we saw a statistically significant difference on the rating scale of ICD symptoms severity, and even a numerical difference on the CGI score, supports additional study of opioid antagonists for ICDs in PD," he said.

"An important consideration for future studies in this area includes having an appropriate primary outcome measure that will be sensitive to changes in symptoms," the authors conclude.

The study was funded by The Michael J. Fox Foundation for Parkinson's Research. Dr. Weintraub has received honoraria from Novartis Pharmaceuticals, Teva Pharmaceuticals, Eli Lilly, Lundbeck Inc, Biogen, Pfizer, Avanir Pharmaceuticals, Merck & Co, UCB, Bristol-Myers Squibb Co, and Clintrex LLC, and licensing fees from the University of Pennsylvania for the QUIP-RS. A complete list of author disclosures is provided with the original article.

Neurology. Published online July 17, 2014. Abstract

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