Context.-The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder; however, empirical support for this assertion has been weaker for children and adolescents than for adults.Objective.-To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessivecompulsive disorder.Design.-Randomized, double-blind, placebo-controlled trial.Patients.-One hundred eighty-seven patients: 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years randomized to receive either sertraline (53 children, 39 adolescents) or placebo (54 children, 41 adolescents).Setting.-Twelve US academic and community clinics with experience conducting randomized controlled trials.Intervention.-Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy, after which patients continued to receive this dosage of medication for 8 more weeks. Control patients received placebo.Main Outcome Measures.-The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH GOCS), and the NIMH Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) rating scales.Results.-In intent-to-treat analyses, patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS (adjusted mean, −6.8 vs −3.4, respectively; P = .005), the NIMH GOCS (−2.2 vs −1.3, respectively; P = .02), and the CGI-I (2.7 vs 3.3, respectively; P = .002) scales. Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study. Based on CGI-I ratings at end point, 42% of patients receiving sertraline and 26% of patients receiving placebo were very much or much improved. Neither age nor sex predicted response to treatment. The incidence of insomnia, nausea, agitation, and tremor were significantly greater in patients receiving sertraline; 12 (13%) of 92 sertraline-treated patients and 3 (3.2%) of 95 placebo-treated patients discontinued prematurely because of adverse medical events (P = .02). No clinically meaningful abnormalities were apparent on vital sign determinations, laboratory findings, or electrocardiographic measurements.Conclusion.-Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder.

Background Behavioral intervention research has lagged behind biomedical research in developing principles for defining, categorizing, identifying, reporting, and monitoring adverse events and unanticipated problems. Purpose In this article we present a set of principles for defining adverse events and how they were applied in a large national multi-site family therapy study for substance-using adolescents, The Brief Strategic Family Therapy (BSFT™) Effectiveness Study. Methods The BSFT™ Effectiveness study tested how BSFT™ compares to Treatment as Usual (TAU) for the treatment of drug-abusing adolescents. During protocol development, experts in the BSFT™ intervention, medical safety officers, ethicists and senior investigators defined the procedures for identifying, tracking and reporting adverse events for drug using adolescents as well as their family members. During this process the team identified five key guiding principles. Results The five guiding principles that were used for defining adverse events in this behavioral trial were that that the adverse events should be validated and plausible, and that monitoring systems should assess relatedness, be systematic, and are a shared responsibility. The following non-serious adverse events were identified: arrest, school suspension and drop out, runaway, kicked out of home and violence. The serious adverse events in this study for the identified adolescent participant and all other consented family members were physical or sexual abuse, suicidal behavior, homicidal behavior, hospitalization (drug related or psychiatric related only) and death. The methods used in categorizing, identifying and reporting adverse events in the BSFT™ trial are outlined. More than 50% of the adolescent population (277/481 = 57.5 %) experienced an adverse event during the trial. Family members experienced less adverse events, (61/1338 = 4.5%). The most common event for the adolescent group was arrest (164/277= 59.2%), followed by school suspension/dropout (143/277 = 51.6%), and runaway (79/277= 28.5 %). For the family member group, the most common event was violence (25/61 = 40.9%) followed by arrest (13/61 = 21.3%). There was a significant difference in the presence of adverse events in family members that were randomized to BSFT™ 44/721 (6.1%) when compared to Treatment as Usual 17/617 (2.8%) (p = 0.004). A probable explanation for this is that there were more opportunities to identify adverse events for family members assigned to BSFT™ because family members attended therapy sessions. This difference may also represent the risk for family members that participate in an evidence-based family intervention like BSFT™. Limitations The utility of the principles outside of the BSFT™ trial is unknown. Conclusions Based on the events reported in this trial, the efforts for monitoring and categorizing adverse events appeared justified and appropriate. The strategies and principles described in this paper may be useful for those developing safety plans for behavioral interventio...

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A multicenter, double-blind placebo-controlled clinical trial was designed to compare the safety and efficacy of estazolam compared with flurazepam as hypnotics. Outpatients complaining of insomnia were randomized to receive either estazolam 2 mg, flurazepam 30 mg or placebo for 7 consecutive nights. The analysis of efficacy was based on the patients' daily assessments of sleep and the investigators' global evaluations. Adverse events which were considered by the investigator to be attributable to, or of unknown relationship to the test medication were analyzed. The patient subjective questionnaire indicated that estazolam and flurazepam significantly improved all parameters (P less than .05) as compared to placebo. A marked or moderate improvement in sleep was reported by 81% (58/72), 78% (63/81) and 36% (27/76) of estazolam, flurazepam, and placebo recipients, respectively. There were no significant differences in hypnotic effect between estazolam and flurazepam. All efficacy parameters of the investigators' global evaluation improved significantly more (P less than .05) for patients receiving estazolam or flurazepam (except quality of sleep) than for those receiving placebo. The percentage of patients reporting any adverse experience was greatest for flurazepam (72%), followed by estazolam (59%), and placebo (43%). Somnolence and hypokinesia were the most commonly reported adverse events. An analysis of the global evaluation of side effects showed that flurazepam had a significantly worse side effect profile than estazolam (P less than .05) or placebo (P = .001). Estazolam and flurazepam effectively, and comparably, relieved insomnia when administered for 7 nights in adult patients complaining of insomnia. Estazolam demonstrated a more favorable side effect profile than flurazepam.

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