Continuation Treatment and Relapse Prevention in Pediatric Depression

The prevalence of depression in children and adolescents ranges from 2% to 8% in the general population, which indicates that depression in this population is a major public health concern.^1-3 This is especially apparent when rates of depression are compared with other serious medical conditions in childhood, such as diabetes, which has a prevalence of 0.18%.⁴ The burden of depressive illness—including significant functional impairment in interpersonal relationships, school, and work—on the developing child has been well documented. Affected youths are frequently involved in the juvenile justice system.^5-8 Furthermore, adolescents with depression are at increased risk for substance abuse, recurrent depression in adulthood, and attempted or completed suicide.^3,9-15

Acute-phase treatments for major depression in this age-group have been found to be effective; however, relapse rates range from 34% to 75%.^16-19 Even with the most effective acute treatments for depression (antidepressant medication with cognitive-behavioral therapy [CBT]), remission rates are low and residual symptoms are common.²⁰ Furthermore, approximately one-third of adolescents with depression are unable to maintain symptom remission.²¹ In addition to acute-phase treatments, it is becoming increasingly accepted that these patients need longer-term treatments (continuation and maintenance phase interventions). See the Table for definitions of key terms.

Risk factors related to relapse

While limited information exists on predictors of relapse in child and adolescent depression, there is evidence that the illness can be recurrent and chronic, as it can be in adults. In particular, the more severe the illness, the greater the risk of recurrence. Predictors of relapse include comorbidity, previous depressive episodes, early age at onset, suicidal thinking and behavior, poor global functioning, psychosocial stressors, family psychiatric history, and family discord.^7,22-31

In the Treatment for Adolescents With Depression Study (TADS), residual symptoms at the end of acute treatment indicated a poorer outcome after acute treatment. Those patients who had symptoms at the end of 12 weeks of treatment were less likely to have symptom remission at 18 and 36 weeks.²¹

Cognitive variables, such as dysfunctional thinking, can predict recurrent depression, and continued cognitive distortions following treatment may predict shorter time to relapse or recurrence of symptoms.^28,32

Continuation-phase treatments

Simons and colleagues³³ describe 3 helpful approaches to understanding treatment strategies for relapse and recurrence prevention in depression (the phases of treatment are defined in the Table):

• Continuation of the acute-phase treatment into the continuation and maintenance phases

• Continuation of the treatment with booster sessions

• Treatments developed specifically for the continuation phase to augment acute outcomes or to prevent relapse and recurrence

Continuation of acute treatment. Placebo-controlled continuation trials in adults have demonstrated that continued pharmacotherapy for 6 to 9 months reduces relapse rates compared with placebo.^34-36 Less is known about how long to continue medication in children and adolescents with depression. In a naturalistic outcome study, Emslie and colleagues²⁵ reported that following acute treatment with fluoxetine(Drug information on fluoxetine), depression recurred at 1 year follow-up in 39% of participants who had been in remission. In a recent randomized controlled trial, the continuation of fluoxetine treatment for 6 months after acute treatment resulted in a lower relapse rate than continuation treatment with pill placebo (42% vs 69%).³⁷ Note the high relapse rate in those who continued their medication.

In addition, continuation-phase cognitive therapy or CBT after acute-phase CBT has been shown to reduce rates of relapse in adults.³⁸ There have been relatively fewer continuation treatment studies using CBT in child and adolescent populations. In an uncontrolled pilot study, Kroll and colleagues³⁹ found that 6 months of continuation-phase CBT (after acute-phase CBT) significantly lowered relapse rates relative to historical controls (6% vs 50%).

Continuation of treatment with booster sessions. Another approach to continuation treatment has been the inclusion of planned booster sessions after acute treatment ends. Clarke and colleagues⁴⁰ reported that booster sessions did not reduce relapse rates, but did accelerate remission in adolescents with depression at the end of the acute-phase CBT treatment. The failure to prevent relapse in this trial may be a consequence of the inadequate number of planned booster sessions (only 1 or 2) and/or poor attendance by participants.

Continuation treatment developed to augment acute treatment response and/or prevent relapse. Continuation-phase CBT after acute-phase pharmacotherapy has been shown to reduce relapse and recurrence in adults and may be cost-effective over time.^41-44 Furthermore, continuation CBT seems to be most effective in patients who exhibit residual symptoms and in those with recurrent depression.^43,45,46