Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
Condition: Obsessive-Compulsive Disorder; Tic Disorders; Tourette Syndrome
MeSH terms: Tourette Syndrome; Tics; Tic Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      This project investigates the use of 4 weeks of 24 mg/day ondansetron as compared to placebo
      on symptoms and brain functioning in patients with obsessive-compulsive disorder (OCD) and
      tic disorders (TD). Patients will be randomized to receive ondansetron or placebo for 4
      weeks, with MRI scans and symptom assessments occurring at baseline (before any drug) and at
      the end of the 4 weeks. Patients will also be asked to come into the lab approximately 2
      weeks into the trial for symptom assessments. The investigators hypothesize that after 4
      weeks there will be greater reduction from baseline in sensory symptoms and the activation of
      the insula and sensorimotor cortex compared for ondansetron as compared to placebo.
    

Detailed description: 
      Many psychiatric disorders are associated with altered sensory experiences arising from
      within the body. Examples include increased experience of sensations or urges in muscles,
      skins, joints or visceral organs in Tic/Tourette's Disorders, OCD patients with symptoms of
      "not just right experiences" or disgust sensitivity, and other disorders such as
      trichotillomania or excoriation disorder. In OCD, these sensory phenomena occur in
      approximately half of patients, are associated with earlier age of onset, and may be harder
      to treat with classic cognitive-behavioral approaches to OCD. Of interest, sensory phenomena
      in OCD are associated with Tourette's syndrome and respond to pharmacological treatments
      primarily used for tics. As such, abnormal sensory processing may be a basic mechanism that
      links various psychiatric disorders.

      The process of attending to body sensations is referred to as interoception, abnormality of
      which may be related to sensory phenomena. Research has revealed a cortical interoceptive
      circuit involving insula, anterior cingulate cortex (ACC), and sensorimotor cortex.
      Ondansetron (OND) is a good candidate for the modulation of the above-described interoceptive
      circuit. It is a selective 5-HT3 (serotonin) receptor antagonist that acts on both peripheral
      and central receptors. OND has long been used to treat nausea and vomiting due to
      chemotherapy, radiation therapy, anesthesia, and opioid-induced emesis. It has also been used
      alone or as adjunctive therapy for the treatment of both OCD and Tourette's disorder, showing
      some efficacy in small clinical trials. The mechanisms by which ondansetron improves symptoms
      in OCD and tic disorders are unknown, although the investigator's earlier study found that
      single doses of ondansetron reduce activation of insula and somatosensory cortex in healthy
      controls. As a follow-up to this work, the current protocol will compare the effects of 24
      mg/day of ondansetron vs. placebo for 4 weeks in patients with OCD or Tic Disorders on
      symptoms and brain functioning.
    

Intervention name(s): Ondansetron; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 5-HT3 (serotonin receptor type 3) antagonist commonly used to treat nausea and vomiting; placebo equivalent
Other intervention name(s): Zofran
Intervention MeSH terms: Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Brain Function; functional magnetic resonance imaging (fMRI); Sensory processing; Obsessive-Compulsive Disorder; OCD