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Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial.

ABSTRACT: Despite the availability of evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them. Tolcapone is a catechol-O-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Conduct a proof of concept study to examine whether a COMT inhibitor would reduce OCD symptoms to a greater extent than placebo. We conducted a randomized, placebo-controlled, double-blind crossover trial in adults with OCD (N = 20). Participants were assessed at baseline, after 2 weeks of tolcapone, and again after 2 weeks of placebo on measures of OCD symptom severity and psychosocial functioning. There was a 1-week washout period between the 2-week treatment phases. Two weeks of tolcapone was associated with significant improvement in OCD versus two weeks of placebo (t = 2.194, P = 0.0409). The mean percentage decreases in the total Yale-Brown obsessive-compulsive scale (YBOCS) scores for the entire sample over the corresponding 2-week period were 16.4% for tolcapone and 3.6% for placebo. These data indicate that brain penetrant COMT inhibitors merit further investigation as a candidate new treatment for OCD.

SUBMITTER: Grant JE

PROVIDER: S-EPMC7611531 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial.

Grant Jon E JE Hook Roxanne R Valle Stephanie S Chesivoir Eve E Chamberlain Samuel R SR

International clinical psychopharmacology 20210901 5

Despite the availability of evidence-based treatments for obsessive-compulsive disorder (OCD), not all patients experience sufficient benefit or are able to tolerate them. Tolcapone is a catechol-O-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Conduct a proof of concept study to examine whether a COMT inhibitor would reduce OCD symptoms to a greater extent than placebo. We conducted a randomized, placebo-controlled, double-blind crossover trial in a ...[more]

PMID: 34310432

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Project description:BackgroundPsilocybin may help treat obsessive-compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin's effects on OCD have also not been studied.ObjectivesThis first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of psilocybin in the treatment of OCD, provide preliminary evidence on the effects of psilocybin on OCD symptoms, and elucidate neural mechanisms that may mediate psilocybin's effects on OCD.DesignWe use a randomized (1:1), double-blind, placebo-controlled, non-crossover design to examine the clinical and neural effects of either a single dose of oral psilocybin (0.25 mg/kg) or active placebo-control agent (250 mg of niacin) on OCD symptoms.Methods and analysisWe are enrolling 30 adult participants at a single site in Connecticut, USA who have failed at least one trial of standard care treatment (medication/psychotherapy) for OCD. All participants will also receive unstructured, non-directive psychological support during visits. Aside from safety, primary outcomes include OCD symptoms over the past 24 h, assessed by the Acute Yale-Brown Obsessive-Compulsive Scale and Visual Analog Scale ratings. These are collected by blinded, independent raters at baseline and the primary endpoint of 48 h post-dosing. Total follow-up is 12 weeks post-dosing. Resting state neuroimaging data will be collected at baseline and primary endpoint. Participants randomized to placebo will be offered the chance to return for an open-label dose of 0.25 mg/kg.Ethics statementAll participants will be required to provide written informed consent. The trial (protocol v. 5.2) was approved by the institutional review board (HIC #2000020355) and registered with ClinicalTrials.gov (NCT03356483).DiscussionThis study may represent an advance in our ability to treat refractory OCD, and pave the way for future studies of neurobiological mechanisms of OCD that may respond to psilocybin.

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Dataset Information

Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial.

Publications

Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial.

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