Tolcapone in Obsessive Compulsive Disorder

The goal of the proposed study is to evaluate the efficacy and safety of tolcapone in adults
with obsessive compulsive disorder (OCD). The hypothesis to be tested is that tolcapone will
be more effective and well tolerated in adults with OCD compared to placebo. The proposed
study will provide needed data on the treatment of a disabling disorder where current
treatments are often ineffective.

The primary aim of this application is to conduct a randomized placebo-controlled
pharmacotherapy trial using tolcapone in 20 participants with OCD. The study will consist of
two phases: a 2 week active treatment phase with tolcapone, a one-week wash-out phase, and a
2 week placebo phase. The subjects will be randomized to either receive tolcapone or placebo
treatment in the first 2 weeks, and the other during the remaining 2 week phase.

This will be one of few studies assessing the use of pharmacotherapy for the treatment of OCD
in adults. Assessing the efficacy and safety of tolcapone will help inform clinicians about
additional treatment options for adults suffering from this disorder.

Inclusion Criteria:

1. Males and females age 18-65;

2. Diagnosis of current OCD based on DSM-5 criteria and confirmed using the
clinician-administered Structured Clinical Interview for DSM-5 (SCID);

3. Able and willing to provide written consent for participation.

Exclusion Criteria:

1. Unstable medical illness, including liver disease, as determined by the investigator;

2. History of seizures;

3. Clinically significant suicidality (defined by the Columbia Suicide Severity Rating
Scale);

4. Baseline score of ≥17 on the Hamilton Depression Rating Scale (17-item HDRS);

5. Lifetime history of bipolar disorder type I or II, schizophrenia, autism, any
psychotic disorder, or any substance use disorder;

6. Initiation of psychotherapy or behavior therapy within 3 months prior to study
baseline;

7. Previous treatment with tolcapone;

8. Any history of psychiatric hospitalization in the past year;

9. Currently pregnant (confirmed by urine pregnancy test)