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Cognitive-Behavior Therapy, Sertraline, and Their Combination for Children and Adolescents With Obsessive-Compulsive Disorder

Background: Cognitive-behavior therapy (CBT) and pharmacotherapy with SSRI’s have been found to be efficacious in the treatment of obsessive-compulsive disorder (OCD), however, there are no published studies comparing CBT, pharmacotherapy with an SSRI, and the combination of both in pediatric populations.

Objective: The purpose of this study was to evaluate the efficacy of CBT alone, medication management with the SSRI sertraline alone, or a combined treatment consisting of CBT and sertraline as initial treatment for children and adolescents with OCD.

Methods: This was a multicenter, randomized, parallel-group clinical trial, evaluating 4 specific treatments including: (1) CBT alone, (2) sertraline alone, (3) combined treatment of CBT and sertraline, and (4) a control condition, consisting of placebo. There were 112 patients ages 7 to 17 included in the trial. The duration of treatment lasted for 12 weeks. Inclusion criteria included the following: receiving treatment as an outpatient, aged 7-17, DSM-IV diagnosis of OCD, a Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) total score greater than 16, NIMH Global Severity Score greater than 7, IQ greater than 80, and being free of antiobsessional medications prior to the start of the study. Exclusion criteria included: presence of major depression or bipolar illness, primary diagnosis of Tourette’s disorder, any pervasive developmental disorder, psychosis, 2 failed SRI trials, CBT therapy for OCD, or any medical or neurological disorder that posed a contraindication to one of the study treatments or that would interfere with the study assessment protocol, and pregnancy. To avoid preselection biases favoring one treatment condition over another, children treated for OCD previously with medication, CBT, or their combination who experienced complete or nearly complete remission of symptoms (defined as a CY-BOCS score less than 6 by retrospective rating) were also excluded. All patients randomly assigned to treatment groups were included in an intent-to-treat analysis. Patients were seen weekly for medication adjustments based on a standard escalating titration schedule which ranged from 25mg/d to 200mg/d over 6 weeks, after which the dosage was adjusted as a function of adverse effects only. The CBT regimen consisted of 14 visits over 12 weeks and involved psychoeducation, cognitive training, mapping OCD target symptoms, and exposure and response prevention. The primary outcomes were the change in CY-BOCS score over 12 weeks as rated by the independent evaluator, and the rate of clinical remission (defined as a CY-BOCS score less than or equal to 10). A nominal significance level was set at a 2-tailed type I error rate of 0.05. Using pilot data from prior studies, the power established prior to study initiation was greater than 99% for the chi-squared test and ≥80% for any pairwise post hoc contrast.

Results: Ninety-seven of the 112 total patients completed the full 12 weeks of treatment. 25 out of 28 completed the CBT alone therapy, 26 out of 28 completed the sertraline alone therapy, 25 out of 28 completed the combined treatment, and 21 out of 28 completed treatment with placebo. The mean (median) numbers of CBT sessions completed out of a possible 14 sessions were: 12(13) and 14(14) in the CBT alone and the combined-treatment groups respectively. The mean(SD) highest daily dose given in the combined group was 133(64)mg, for the sertraline alone group it was 170(33)mg, and for the placebo equivalents it was 176(40)mg. The corresponding median doses for combination treatment, sertraline alone, and placebo were 150, 200, and 250 mg respectively. For the primary outcome of change in CY-BOCS score, the combined treatment was superior to CBT alone (P=0.008), to sertraline (P=0.006), and to placebo (P<0.001). There was no statistical significance between CBT alone and sertraline alone (P=0.80) in change in CY-BOCS score. Both the CBT alone and the sertraline alone were statistically superior to placebo (P=0.007). Patients achieving clinical remission (CY-BOCS<10) in the combined treatment group was (53.6%; 95% CI, 36%-70%) and did not differ from CBT alone (39.3%; 95% CI, 24%-58%) (P=0.42). The combined treatment did differ from sertraline (21.4%; 95%CI, 10%-40%) (P=0.03) and it did differ from placebo (3.6%; 95% CI, 0%-19%) (P<0.001). The use of CBT alone did not differ from sertraline (P=0.24) but did differ from placebo (P=0.002). Sertraline did not differ from placebo (P=0.10). There were no episodes of mania, hypomania, or depression, and no serious adverse events occurred during the course of the study. Most importantly, no patient became suicidal or made a suicide attempt. The authors concluded that children and adolescents with OCD should begin treatment with CBT alone or with CBT plus an SSRI.

Strengths: This is the first published study comparing CBT, pharmacotherapy with a SSRI, and their combination with a control group in the same patient population. All statistical analyses used were appropriate. The authors talked about future papers which would address the main question that clinicians ask: which treatment should be used for which child with which specific set of clinical characteristics. The independent evaluators were trained to a reliable standard on the tests used to asses OCD severity.

Weaknesses: It was not known if the power of the study held through because the parameters used to obtain that power were not given, making Type II error a possibility. There was variability seen in effect sizes between the sertraline and CBT groups at Duke and Penn (Duke showed a larger effect size of sertraline vs. CBT and Penn showed a larger effect size of CBT vs. sertraline). Because of this large difference, CBT use as an initial treatment was not substantiated by all of the results. Although the CBT manual provided flexibility to accommodate the developmental stage of the child, there is a marked difference in the level of understanding between a 7 year old and a 17 year old. Having the participants separated into subgroups, allowing a comparison of smaller age ranges would have been beneficial to assess any differences age made in the results. It was not clear which CY-BOCS score truly yielded clinical remission because in the exclusion criteria it was a score less than 6, however when computing the results for the study, it was less than 10. An analysis of results for responders vs. nonresponders to sertraline would have provided additional information as to the actual efficacy of sertraline. There was no CBT/placebo group to keep the CBT/sertraline group blinded during the trial. The authors did not mention patients who had used sertraline and did not respond in the past in the exclusion criteria. Compliance was mentioned during the methods section, however, it was never reported in the results.

Conclusions: Due to the limitations of the study, it is not clear whether or not CBT alone or in combination with sertraline should be used as first line treatment in children and adolescents with OCD. Availability of CBT to all patients and the quality of CBT provided are also concerns that should be addressed. Future studies should include the treatment with various SSRI’s rather than one specific medication due to the fact that not all people will respond to sertraline, resulting in the use of a different SSRI. Also, because of the variability of CBT results at two well-known medical institutions, it would be useful to also include results from CBT at institutions that do not specialize in that specific therapy to see if it has any significant effect on the results.

March JS, Foa E, Gammon P, Chrisman A, Curry J, Fitzgerald D, et al. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder. JAMA 2004;292(16):1969-76.

Monica Pathak, PharmD Candidate