Naltrexone for Impulse Control Disorders in Parkinson's Disease

Impulse control disorders (ICDs), including compulsive gambling, sexual behavior, buying,
and eating, are increasingly recognized as a significant clinical problem in Parkinson's
disease (PD), occurring in up to 15% of patients. Dopamine agonist (DA) treatment is thought
to be the primary risk factor for the development of ICDs in PD. ICDs often lead to
significant impairments in psychosocial functioning, interpersonal relationships, and
quality of life. The management of ICDs in the context of PD can be complex. Patients may be
reluctant to discontinue DA treatment due to the motor benefits derived from treatment, so
patients often have chronic symptoms. Thus, additional treatment approaches are needed.

A medication shown to be efficacious for the treatment of ICDs with minimal impact on
parkinsonism would allow many ICD patients to continue on full-dose DA treatment.
Naltrexone, a long-acting opioid receptor antagonist, helps in the treatment of alcohol and
opioid dependence. In addition, placebo-controlled studies have demonstrated that it helps
in the treatment of pathological gambling in the general population. Opioids regulate
dopamine pathways in areas of the brain linked with impulse control disorders, and opioid
antagonists block opioid receptors in these regions. In this study, 48 PD patients with an
ICD will be treated either with naltrexone (50-100 mg/day) or placebo for a period of 8
weeks. The study will assess if naltrexone improves ICD symptoms in PD and is well
tolerated. To our knowledge, the proposed study is the first controlled trial of an agent to
treat ICDs in PD.

Inclusion Criteria

1. Diagnosis of possible or probable idiopathic Parkinson's disease (PD).

2. Ages 18-85 years.

3. Diagnosis of compulsive gambling, buying, sex behavior, or eating of >2 months
duration.

4. Impulse control disorder (ICD) behaviors that began after PD onset and in context of
dopamine agonist (DA) treatment.

5. Current stable DA use. Participants must be on a DA for 6 months and on a stable dose
(no changes) for 1 month prior to enrolling the in the study.

6. Subjects are capable of giving informed consent, supported by not having significant
cognitive impairment based on Montreal Cognitive Assessment score ≥24.

7. Willingness to maintain existing PD pharmacotherapy regimen for the duration of the
study.

Exclusion Criteria

1. Active suicide ideation.

2. Anticipated need to initiate antidepressant therapy during the course of the study
(must be on a dose in the therapeutic range for at least 2 months. If patient does
end up needing to start antidepressant or change antidepressant dose during the
course of the study, he/she will be allowed to continue study participation).

3. ICD behaviors so severe that modification of DA treatment is clinically warranted, as
judged by PI.

4. Deep brain stimulation surgery in the past year.

5. Evidence for significant liver disease by chart review or patient history (e.g.,
cirrhosis, chronic hepatitis, liver transplant, or liver cancer).

6. Meeting diagnostic criteria for alcohol or opiate dependence.

7. Meeting diagnostic criteria for Dopamine Dysregulation Syndrome.

8. Use of opioids for pain management.

9. Females that are pregnant, planning to become pregnant, or are breastfeeding will not
be included in the study. Females of child bearing potential will need to verify that
they are not pregnant by a negative urine pregnancy test.