Obsessive-Compulsive Disorder
Conditions
Keywords
OCD, Antidepressive Agents, Second-Generation, Placebos, Cognitive Behavior Therapy, Child Psychiatry, Activation Syndrome, Psychometrics
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.
Interventions
DRUGRegular Titration
Sertraline will be administered in standard dosing. Treatment with sertraline will last 18 weeks.
DRUGPlacebo
The placebo will be administered in the same manner as sertraline. Treatment with placebo will last 18 weeks.
DRUGSlow Titration
Sertraline will be administered in slow titration. Treatment with sertraline will last 18 weeks.
Sponsors
National Institute of Mental Health (NIMH)
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
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, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Severity of Activation (CGI-SA) | 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 | 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). |
Countries
United States
Participant flow
Recruitment details
The study was performed at two child and adolescent psychiatric clinics within university medical centers: Gainesville, Florida (FL) (UF) and Tampa, FL (USF). Recruitment started in early 2009 and ended in late 2010.
Pre-assignment details
Fifteen participants were excluded after screening: 7/15 did not meet inclusion/exclusion criteria and 8/15 withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo plus cognitive behavior therapy. | 18 |
| Regular Titration Regular titration of sertraline plus cognitive behavior therapy. | 17 |
| Slow Titration Slow titration of sertraline plus cognitive behavior therapy. | 21 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Temporary study suspension | 2 | 2 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Regular Titration | Slow Titration | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 17 Participants | 21 Participants | 56 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 13 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 18 | 12 / 17 | 18 / 21 |
| serious Total, serious adverse events | 1 / 18 | 1 / 17 | 0 / 21 |
Outcome results
Primary
Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score
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).
Time frame: Measured at Week 18 or End of Study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score | 16.28 units on a scale | Standard Deviation 7.11 |
| Regular Titration | Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score | 16.35 units on a scale | Standard Deviation 9.6 |
| Slow Titration | Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score | 17.67 units on a scale | Standard Deviation 7.28 |
Comparison: Data were analyzed using ANCOVA modeling with two-sided testing and level of significance = .05. The dependent variable was last measured CY-BOCS score, the independent variable was randomized group assignment and the covariate was the CY-BOCS score at baseline. The null hypothesis was that there were no group differences.p-value: 0.8831ANCOVA
Primary
Clinical Global Impression - Severity of Activation (CGI-SA)
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.
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
Population: Per protocol, Intent to treat
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression - Severity of Activation (CGI-SA) | .50 units on a scale | Standard Deviation 1.5 |
| Regular Titration | Clinical Global Impression - Severity of Activation (CGI-SA) | 2.00 units on a scale | Standard Deviation 1.35 |
| Slow Titration | Clinical Global Impression - Severity of Activation (CGI-SA) | 2.00 units on a scale | Standard Deviation 1.28 |
Comparison: Data were analyzed using two-sided Kruskal-Wallis test with level of significance = .05. Null hypothesis was that there were no group differences. The maximum CGI-SA obtained over course of study was the outcome measure.p-value: 0.2106Kruskal-Wallis