Clinical trial NCT00382291: Effectiveness of Sertraline and Cognitive Behavioral Therapy in Treating Pediatric Obsessive-Compulsive Disorder
Official title: SSRI-Induced Activation Syndrome in Pediatric Obsessive Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obsessive-Compulsive Disorder
Keywords: OCD
Antidepressive Agents, Second-Generation
Placebos
Cognitive Behavior Therapy
Child Psychiatry
Activation Syndrome
Psychometrics
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2006-09-29
Enrollment: 56
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Clinical Global Impression - Severity of Activation (CGI-SA)
timeFrame: Measured at screening, baseline and weekly until end of week 8 after baseline, then monthly for two months and finally at end of study
measure: Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score
timeFrame: Measured at Week 18 or End of Study
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
Study officials:
affiliation: University of South Florida
name: Tanya K. Murphy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Regina Bussing, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.