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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00382291
First received: September 28, 2006
Last updated: February 6, 2013
Last verified: December 2012
  Purpose

This study measures the occurrence of certain side effects linked to antidepressant use and evaluates the effectiveness of the medication sertraline plus cognitive behavioral therapy to treat people with obsessive-compulsive disorder.


Condition Intervention Phase
Obsessive-Compulsive Disorder
Drug: Regular Titration
Drug: Placebo
Drug: Slow Titration
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: SSRI-Induced Activation Syndrome in Pediatric Obsessive Compulsive Disorder

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Clinical Global Impression - Severity of Activation (CGI-SA) [ Time Frame: Measured at screening, baseline and weekly until end of week 8 after baseline, then monthly for two months and finally at end of study ] [ Designated as safety issue: Yes ]
    The CGI-SA was adapted from the Clinical Global Impressions - Severity of Illness (CGI-SI) rating (Guy, 1976). The CGI-SI is commonly used in clinical studies of children and adults and has been extensively validated (Zaider et al., 2003). On the CGI-SA clinicians rate the severity of activation symptoms on a range from 0 (no activation) to 7 (extremely severe symptoms, functionally highly impaired and/or extreme distress). We report values representing Median+/-Std Dev for the maximum CGI-SA obtained over the course of study.

  • Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score [ Time Frame: Measured at Week 18 or End of Study ] [ Designated as safety issue: No ]
    The CY-BOCS (Scahill et al., 1997) is a semi-structured, clinician rated instrument to measure OCD symptom severity in youth. The CY-BOCS contains a symptom checklist and a severity scale. Through the symptom checklist the clinician assesses current and past experiences of over 60 potential obsessions and compulsions. The Total Score represents the sum of obsession severity and compulsion severity which each consist of five clinician ratings on a Likert scale (range from 0 (none) to 4 (extreme), for time spent, interference, distress, resistance and control over symptoms). Summing of obsession and compulsion severity (range 0-20 on each) produces the Total CY-BOCS score (range 0-40, with 0 representing the best and 40 the worst outcome). Studies have documented good psychometric properties of the CY-BOCS (Gallant et al., 2008; Scahill et al., 1997; Storch et al., 2004).


Enrollment: 56
Study Start Date: February 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regular Titration
Regular titration of Sertraline plus cognitive behavioral therapy. The titration schedule used a flexible upward titration from 25 mg/day to 200 mg/day over 9 weeks unless higher doses were not tolerated, after which the dosage was adjusted as a function of tolerability. If tolerated, maximum dose could be achieved in 5 weeks.
Drug: Regular Titration
Sertraline will be administered in standard dosing. Treatment with sertraline will last 18 weeks.
Placebo Comparator: Placebo
Placebo plus cognitive behavioral therapy
Drug: Placebo
The placebo will be administered in the same manner as sertraline. Treatment with placebo will last 18 weeks.
Experimental: Slow Titration
Slow titration of Sertraline plus cognitive behavior therapy. The titration schedule utilized a slower titration schedule relative to the RegSert arm. Unless unable to tolerate higher doses, children remained on 25mg/day for the first two weeks, 50mg/day from weeks 3-4, 75mg/day for weeks 5-6, 100mg/day for week 7, 150mg/day for week 8, and 200mg/day for week 9 until the end of the study.
Drug: Slow Titration
Sertraline will be administered in slow titration. Treatment with sertraline will last 18 weeks.

Detailed Description:

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 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.

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 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.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, attention deficit hyperactivity disorder, 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00382291

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
University of South Florida
Tampa, Florida, United States, 33701
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Tanya K. Murphy, MD University of South Florida
Principal Investigator: Regina Bussing, M.D. University of Florida
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00382291     History of Changes
Other Study ID Numbers: R01 MH078594, R01MH078594, DSIR 84-CTM
Study First Received: September 28, 2006
Results First Received: December 14, 2012
Last Updated: February 6, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Florida:
OCD
Antidepressive Agents, Second-Generation
Placebos
Cognitive Behavior Therapy
Child Psychiatry
Activation Syndrome
Psychometrics

Additional relevant MeSH terms:
Obsessive-Compulsive Disorder
Compulsive Personality Disorder
Anxiety Disorders
Mental Disorders
Personality Disorders
Antidepressive Agents
Sertraline
Antidepressive Agents, Second-Generation
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014