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

• ClinicalTrials.gov Identifier: NCT00382291
• Recruitment Status: Completed
• First Posted: September 29, 2006
• Results First Posted: March 12, 2013
• Last Update Posted: March 12, 2013
• Sponsor: University of Florida
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): University of Florida

Tracking Information

• First Submitted Date: September 28, 2006
• First Posted Date: September 29, 2006
• Results First Submitted Date: December 14, 2012
• Results First Posted Date: March 12, 2013
• Last Update Posted Date: March 12, 2013
• Study Start Date: February 2009
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 6, 2013)

• 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 ]
  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 ]
  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).

• Original Primary Outcome Measures (submitted: September 28, 2006): Our primary comparison of interest will be the performance of the sertraline at standard dosing and placebo groups on both the TE-ASAP and existing behavioral measures of irritability, impulsivity/aggression, restlessness and mania.
• Change History: Complete list of historical versions of study NCT00382291 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: September 28, 2006): We will explore if sertraline slowly increased reduces the frequency or intensity of activation syndrome compared to sertraline at standard dosing.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effectiveness of Sertraline and Cognitive Behavioral Therapy in Treating Pediatric Obsessive-Compulsive Disorder
• Official Title: SSRI-Induced Activation Syndrome in Pediatric Obsessive Compulsive Disorder
• Brief Summary: 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.

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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Diagnostic
• Condition: Obsessive-Compulsive Disorder

Intervention

• Drug: Regular Titration
  Sertraline will be administered in standard dosing. 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.
• Drug: Slow Titration
  Sertraline will be administered in slow titration. Treatment with sertraline will last 18 weeks.

Study Arms

• 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.
  Intervention: Drug: Regular Titration
• Placebo Comparator: Placebo
  Placebo plus cognitive behavioral therapy
  Intervention: Drug: Placebo
• 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.
  Intervention: Drug: Slow Titration

Publications *

• Bussing R, Murphy TK, Storch EA, McNamara JP, Reid AM, Garvan CW, Goodman WK. Psychometric properties of the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) in youth with OCD. Psychiatry Res. 2013 Feb 28;205(3):253-61. doi: 10.1016/j.psychres.2012.09.019. Epub 2012 Sep 29.
• Reid AM, McNamara JP, Murphy TK, Guzick AG, Storch EA, Goodman WK, Geffken GR, Bussing R. Side-effects of SSRIs disrupt multimodal treatment for pediatric OCD in a randomized-controlled trial. J Psychiatr Res. 2015 Dec;71:140-7. doi: 10.1016/j.jpsychires.2015.10.006. Epub 2015 Oct 14. Erratum in: J Psychiatr Res. 2016 Mar;74:94. Goodman, Wayne K [added].
• Bussing R, Reid AM, McNamara JP, Meyer JM, Guzick AG, Mason DM, Storch EA, Murphy TK. A pilot study of actigraphy as an objective measure of SSRI activation symptoms: results from a randomized placebo controlled psychopharmacological treatment study. Psychiatry Res. 2015 Feb 28;225(3):440-5. doi: 10.1016/j.psychres.2014.11.070. Epub 2014 Dec 10.
• Storch EA, Bussing R, Small BJ, Geffken GR, McNamara JP, Rahman O, Lewin AB, Garvan CS, Goodman WK, Murphy TK. Randomized, placebo-controlled trial of cognitive-behavioral therapy alone or combined with sertraline in the treatment of pediatric obsessive-compulsive disorder. Behav Res Ther. 2013 Dec;51(12):823-9. doi: 10.1016/j.brat.2013.09.007. Epub 2013 Oct 10.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 26, 2012): 56
• Original Enrollment (submitted: September 28, 2006): 140
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00382291
• Other Study ID Numbers: R01MH078594( U.S. NIH Grant/Contract ); R01MH078594 ( U.S. NIH Grant/Contract ); DSIR 84-CTM
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Florida
• Study Sponsor: University of Florida
• Collaborators: National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Tanya K. Murphy, MD; University of South Florida
• Principal Investigator: Regina Bussing, M.D.; University of Florida

• PRS Account: University of Florida
• Verification Date: December 2012