Effectiveness of Sertraline and Cognitive Behavioral Therapy in Treating Pediatric Obsessive-Compulsive Disorder

Official Title: “SSRI-Induced Activation Syndrome in Pediatric Obsessive Compulsive Disorder”

This study will develop and evaluate a new behavioral test to measure certain side effects linked to antidepressant use and will evaluate the effectiveness of the medication sertraline plus cognitive behavioral therapy to treat people with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is an anxiety disorder that is associated with recurring repetitive behaviors and persistent unwanted thoughts. People with OCD often carry out ritual-like behaviors such as counting, cleaning, or washing their hands in order to momentarily ease their anxiety. A current treatment for people with OCD is the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). A recent re-analysis of clinical trials on children with psychiatric conditions found that the risk of suicidal thoughts and behavior when on SSRI-antidepressants was considerably higher than when on placebo. The data also revealed that antidepressant-associated suicidal behavior was not limited to children with depression, but also affected children with OCD and other anxiety disorders. Although the process responsible for increased suicidality is unknown, it may be initiated by a set of symptoms collectively called SSRI induced activation syndrome, which is thought to be common, particularly in children and teens. However, there is a lack of knowledge on this syndrome, including its role in suicidal behavior and how it can be prevented. This study will develop and evaluate a new behavioral test to measure certain side effects linked to antidepressant use. This study will also evaluate the effectiveness of the SSRI sertraline plus cognitive behavioral therapy (CBT) to treat people with OCD.

This double-blind study will be divided into two phases. Phase 1 will involve the development and evaluation of a new behavioral test to measure antidepressant side effects.

Participants will attend a 2-hour screening interview during which they will be asked to describe any side effects experienced from antidepressant medications and to rate how problematic these side effects are for them. Participants will be contacted by phone 1 week later to answer questions repeated from the interview. Participation in Phase 1 will last about 10 days.

Phase 2 will comprise the medication treatment portion of the study. Potential participants will undergo an initial screening visit that will include an interview on psychological symptoms associated with OCD and possible family history of OCD. Eligible participants will then undergo a physical exam, blood draw, DNA sampling, and pregnancy test if applicable.

Participants will be randomly assigned to receive either sertraline or placebo daily for 18 weeks. At weekly study visits, participants will receive their study drug, complete questionnaires about symptoms of OCD, and undergo vital sign measurements. At specified visits, participants will also perform a task (Stop Signal Task) on a computerized assessment device to measure attention and impulse control and may have blood drawn. For the first 4 weeks of Phase 2, participants will wear a wristwatch-like device (actigraph) to monitor sleep patterns. During the first three visits, participants will receive supportive psychotherapy. At Visit 4, participants will begin receiving 60-minute CBT sessions, which will continue until the final visit. The final visit will include a second physical exam, questionnaires, and blood testing.

Intervention(s) in this Clinical Trial

• Drug: Sertraline
  • Sertraline will be administered in standard dosing or slow titration. Treatment with sertraline will last 18 weeks.
• Drug: Placebo
  • The placebo will be administered in the same manner as sertraline. Treatment with placebo will last 18 weeks.
• Behavioral: Cognitive behavioral therapy (CBT)
  • CBT treatment will begin at Week 4 of antidepressant treatment. CBT will include education, training, and identifying repetitive behaviors of participants. Participants will learn how to respond to repetitive behaviors in a positive manner.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Sertraline and cognitive behavioral therapy
• Active Comparator: 2
  • Placebo and cognitive behavioral therapy

Primary Measures

• Performance of sertraline versus placebo on both the TE-ASAP and existing behavioral measures of irritability, impulsivity/aggression, restlessness, and mania
  • Time Frame: Measured at Week 18
    Safety Issue?: No

Secondary Measures

• Comparison of slowly increased doses of sertraline versus sertraline at standard dosing for reducing the frequency or intensity of activation syndrome
  • Time Frame: Measured at Week 18
    Safety Issue?: No

Inclusion Criteria:

• Principal diagnosis of OCD with at least a 6-month duration, as determined by structured clinical interview (schedule for affective disorders and schizophrenia for school-age children)
• As long as OCD is the principal diagnosis, co-morbid depression, ADHD, tic disorder, or another anxiety disorder is allowable
• Diagnosis of trichotillomania or body dysmorphic disorder provided OCD symptoms are the predominant presenting features
• Meets clinical criteria for Pediatric Autoimmune Neuropsychiatric Disorders
• Associated with Streptococcal Infections (PANDAS) (e.g., abrupt onset and dramatic fluctuations in symptoms)

Exclusion Criteria:

• Prior adequate trial of sertraline
• Allergy to sertraline
• History of rheumatic fever or serious autoimmune disorder
• Diagnosis of bipolar disorder, autism, schizophrenia, mental retardation, or chronic degenerative neurological disease
• Current anorexia nervosa with symptoms of body image distortion (symptoms of anorexia secondary to obsessions [e.g., contamination] are permitted)
• Unable to safely swallow study medication after pill swallowing education
• Unwillingness of children's parents to commit to accompanying their child for multiple study visits and to be responsible for medication compliance
• Suicidal intent (suicidal ideation will not be an automatic exclusion; however, risk will be gauged carefully and the participant must contract for safety)
• Suicide attempt in the 12 months prior to study entry
• Pregnancy
• Taking monoamine oxidase inhibitors (MAOIs) within 4 weeks of study entry or fluoxetine within 5 weeks of study entry
• Taking other psychotropic medications other than sedative or hypnotics for insomnia
• Substance abuse or dependence within 6 months prior to study entry

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 7 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Florida Other

Overall Clinical Trial Officials and Contacts

Tanya K. Murphy, MD Principal Investigator University of South Florida  

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00382291

Study ID Number: R01 MH078594

ClinicalTrials.gov Identifier: NCT00382291

Health Authority: United States: Federal Government