Achievement and maintenance of sustained response during the treatment for adolescents with depression study continuation and maintenance therapy

Given the high probability of relapse and recurrence following favorable response to treatment in depressed adults and adolescents1,2, guidelines have been developed to extend beyond acute treatment. The goal of continuation treatment is to prevent relapse following remission (i.e., the initial period during which the person has responded to treatment3), whereas the goal of maintenance treatment is to prevent recurrence following recovery (i.e., once the person has been symptom-free long enough to consider the initial depressive episode over). Little is known concerning effective continuation and maintenance therapies for depressed adolescents, and practice guidelines for adolescents4,5 have been adopted from the larger body of guidelines for long-term treatment of depressed adults6,7,8,9. Previous post-acute treatment research with depressed adolescents is extremely limited. A six-month course of cognitive behavioral therapy (CBT) continuation treatment in 17 patients (ages 11-17) following acute CBT10 was superior to no treatment in a historical control group of 12 patients, and fluoxetine continuation treatment was superior to pill placebo in reducing depression relapse among 40 patients (ages 8-18) who had responded to fluoxetine acute treatment11. In the former study, cumulative relapse risk was 20% among continuation CBT patients versus 50% among historical controls. In the latter study, relapse, which was defined as either a Children's Depression Rating Scale-Revised (CDRS-R12) score > 40 or physician opinion over a 32-week post-acute phase, occurred in 34% of patients who remained on fluoxetine versus 60% of those switched to placebo. In the only study to our knowledge that evaluated a maintenance treatment for adolescent depression, Clarke and colleagues13 examined the degree to which an individual CBT booster intervention reduced depression recurrence. After an 8-week, 16-session group CBT intervention, one-third of the 54 adolescents (ages 14-18) who completed treatment (regardless of response status) were randomly assigned to individual boosters every four months over a 2-year follow-up. The booster condition was not associated with less depression recurrence among recovered patients (27% recurrence among booster patients versus 8% among assessment-only controls, ns) but did significantly improve the rate of recovery for adolescents who were still depressed following acute treatment (100% recovery among booster patients versus 50% among assessment-only controls, p < .05). This study suggests that an important function of post-acute treatments may be to facilitate continued improvement among partial responders. The goal of the present study was to examine the rates of sustained improvement during continuation and maintenance therapies in the Treatment for Adolescents with Depression Study (TADS; The TADS Team14,15,16). TADS is a randomized controlled trial that evaluated the effectiveness of three treatments for adolescents with major depressive disorder (MDD): fluoxetine pharmacotherapy with clinical management (FLX), cognitive-behavior therapy (CBT), and the combination of FLX and CBT (COMB), relative to clinical management with pill placebo (PBO). TADS treatment was provided in three stages: (I) acute treatment lasting 12 weeks, (II) continuation treatment lasting 6 weeks and varying in intensity based on the patient's response to acute treatment, and (III) maintenance treatment lasting 18 weeks, in which patients met with their clinician(s) three times and, if applicable, continued medication. Previous publications reported that the COMB and FLX conditions had higher response rates than CBT or PBO during Stage I14, and COMB performed better during Stages II and III than either of the monotherapies, which had very similar response rates17. Our outcome measure in the present study is Sustained Response, which is defined as two consecutive ratings of a full response in assessments conducted 6 weeks apart. TADS follow-up did not include the collection of weekly symptom ratings necessary to determine recovery and recurrence3,18. Our creation of the sustained response variable provides an alternative outcome that answers important questions in clinical decision making that must be answered before a patient is considered recovered (e.g., Is my patient responding to this treatment? Is this apparent response more than transitory? Should I augment treatment or change modalities?). Although it was not an original aim of TADS, data during TADS continuation and maintenance therapies provided a unique and valuable opportunity to address two issues: (1) to what degree do patients who have not achieved sustained response during acute therapy subsequently achieve sustained response during continuation and maintenance therapies, and (2) among patients who achieved sustained response during acute therapy, how many maintain their sustained response through continuation and maintenance therapies. The present study extends the previous Stage III TADS publication17 by requiring a maintained response rather than the one time achievement of a positive response and by examining the degree to which sustained response is maintained once achieved. In addition, although data on treatment adherence and compliance following acute treatment were not available, we examine, as a secondary aim, whether treatment modalities differed in rates of attendance, which serves as one basic indicator of treatment utilization. Retaining the patient is a basic gauge of the perceived value of post-acute care. In addition, differences in the rates of sustained response may be influenced by condition differences in attendance. One possible explanation for the nonsignificant recurrence prevention finding of the booster protocol in Clarke et al.13 was that many adolescents assigned to booster therapy (perhaps more than half) failed to attend post-acute treatment. Although we are unable to evaluate the degree to which patients complied with continuation and maintenance therapies in TADS, we compared whether treatment attendance varied across conditions.