Maintenance Study for Adolescent Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      This study examined the benefit of continued treatment with an antidepressant medication,
      sertraline, in adolescents with depression who improved on sertraline acutely. We hypothesize
      that adolescents who remained on sertraline long term were less likely to have a recurrence
      of depression compared to those on placebo.
    

Detailed description: 
      This study was designed as a randomized controlled trial of maintenance treatment of
      sertraline in adolescents aged 13-19 with depression.

      Subjects Subjects aged 13-19 were recruited, over 18 months, at mood disorders clinics in 3
      tertiary care centres across Canada. Informed consent was obtained from eligible and
      interested subjects and parents (if subject <16 years of age). Subjects were eligible for
      entry into the study if they had a diagnosis of Major Depression determined from both
      clinical interview and the Schedule for Affective Disorders and Schizophrenia for Children
      (K-SAD-PL) and scored > 16 on the first 17 items of the 29-item Hamilton Rating Scale for
      Depression (HAM-D). Subjects were excluded if they had past or current hypomanic or manic
      episode, current psychotic symptoms, substance dependence in the last 3 months, significant
      medical condition that would contra-indicate the use of antidepressants or that if untreated
      may require medical attention, pregnancy, or past treatment with sertraline for major
      depression.

      Interventions and Procedures There were 3 phase to the study: 1) a 12-week acute phase, 2) a
      24-week continuation phase, and 3) a 52-week maintenance phase. In general, subjects were
      assessed every 2 weeks throughout the study except during the first 4 weeks of the
      maintenance phase when they were seen or contacted weekly. In the continuation and
      maintenance phases, every 2nd visit was conducted in person while the other assessments could
      be conducted either by telephone or in person.

      Initial sertraline dose during the acute phase was either 25 mg or 50 mg daily with increases
      of 25 to 50 mg every 2 weeks at the treating clinicians' discretion, up to a maximum of 200
      mg daily. For responders who entered the continuation phase and had some re-emergence of
      symptoms without relapse, dose increases with sertraline were permitted every 2 weeks to a
      maximum dose of 200 mg daily but only during the first 8 weeks of the continuation phase. If
      a subject experienced side effects, one dose decrease was permitted in the first 8 weeks of
      the continuation phase. Subjects who maintained response during continuation were then
      randomized to continue sertraline or to take placebo. In the placebo group, sertraline was
      tapered by 25% of the initial dose every week for the first 4 weeks of the maintenance phase.
      During the maintenance phase, no treatment changes were permitted.

      Subjects who responded to acute phase treatment, defined as 2 consecutive HAMD < 9 and
      greater than a 50% reduction in HAM-D score within 12 weeks, were offered entry into the
      continuation phase. Inter-rater reliability for the HAM-D was tested annually with site
      project coordinators and research assistants. Further training and evaluation were
      implemented until the inter-rater reliability was 0.8 or greater. Relapse during the
      continuation and recurrence during maintenance phases were determined according to the
      clinical judgement of the treating physician that the major depression had recurred or an
      intervention beyond what was permitted by the study protocol was required.

      Adverse events were collected using the Common Adverse and Side Effects Scale. The scale was
      administered every 2 weeks during the acute phase and every 4 weeks during the continuation
      and maintenance phase.

      Blinding and Randomization Randomization was conducted by the study pharmacist using a
      computer generated randomization schedule. Subjects, clinicians and research staff remained
      blinded to treatment during the randomization phase. All statistical analyses were conducted
      by an independent statistician blinded to patient allocation.
    

Intervention name(s): Sertraline; placebo
Intervention type(s): Drug; Drug
Intervention description(s): maintenance treatment with sertraline; placebo
Other intervention name(s): zoloft
Intervention MeSH terms: Sertraline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: depression; adolescents; maintenance treatment; antidepressant