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, 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

In a recent pilot study in depressed youths (aged 11 to 18 years), continuation-phase CBT combined with continuation pharmacotherapy reduced the risk of relapse 8-fold compared with continuation medication alone.^47,48 Furthermore, the addition of CBT after acute-phase pharmacotherapy increased the length of time to relapse, which supports the use of a sequential treatment strategy in pediatric depression.⁴⁸

Clinical applications

Acute-phase interventions, including treatment with antidepressant medications and specific psychotherapies, show promise in treating depression in children and adolescents. The combination of fluoxetine and CBT is the most effective.¹⁷ There are relatively few therapists trained in CBT, and monotherapy with medication may therefore be worth considering as an acute strategy. Monotherapy with CBT is also effective but may require a longer treatment duration to achieve remission.²¹

The gold standard for a positive outcome is to treat depression to remission.⁴⁹ To assess remission status, it is useful to employ a measure of depressive symptoms to monitor residual symptoms that may warrant more clinical intervention. Residual symptoms increase the risk of relapse. Furthermore, residual symptoms after 12 weeks of treatment may predict failure to achieve later remission. Common residual symptoms in adolescents treated for depression include sleep disturbances, low mood, fatigue, and poor concentration.²⁰

Treatment continuation is critical. While much of the focus in the literature has been on developing effective acute treatments, little attention has been given to later-phase interventions. As with adults, youths may experience multiple episodes and, thus, continued symptom management is needed. In addition to the normal developmental stressors experienced in youths that make treating this population difficult, continuation-phase treatment presents new challenges. These include keeping the youth engaged in treatment after symptom improvement and maintaining adherence.

Proposed model for the treatment of depressed youth

Based on the literature, we have developed a sequential treatment strategy whereby we initiate antidepressant treatment in the acute phase (6 to 12 weeks) and monitor symptoms and outcomes. Once response is attained, we add relapse-prevention CBT to target residual symptoms and foster remission. At the initiation of treatment, we collaborate with the youth to develop the timeline-a tool that integrates case conceptualization and treatment planning (Figure). Relapse-prevention CBT includes psychoeducation about depression and core skills, including behavioral activation, problem solving, and cognitive restructuring.

Once remission is achieved, wellness skills are introduced. Wellness training includes building on the patient’s strengths and promoting activities that elevate his or her mood and sense of self-worth (self-care and soothing, social skills, self-adopted goals, mastery and success, spirituality, and self-acceptance). A family component provides psychoeducation about risk of relapse and ways to support the patient to achieve or maintain remission; it also includes teaching ways to reduce expressed emotion and to improve family communication and problem solving as well as family wellness.

Treatment culminates with the development of an individual and family relapse-prevention and wellness plan. Therapy is modified to accommodate different levels of development (eg, using more behavioral skills and frequent family sessions for younger patients).

Case Vignette

Travis is a 10-year-old who presented with his first episode of major depressive disorder to the outpatient psychiatry clinic. His symptoms at baseline included depressed mood, irritability, anhedonia, feelings of worthlessness/negative self-image, fatigue, concentration difficulties, sleep disturbance, increased appetite, and suicidal ideation. In addition, he reported high levels of family stress and chaos and feeling “unimportant.” Although he had been a good student, his academic performance had declined. His baseline depression severity, as assessed by a clinician rating scale of depression, indicated severe depressed mood.

Treatment response was seen at 6 weeks of open treatment with fluoxetine, although he was not yet in remission. At that point, relapse-prevention CBT was initiated to address the remaining symptoms, which included mild depressed mood, irritability, sleep problems, and negative self-image.

Psychotherapy consisted of 12 sessions over 6 months. To address continued mood problems, behavioral coping strategies were developed collaboratively between Travis and his therapist. Sleep hygiene practices were introduced to improve sleep. In addition, the therapist introduced cognitive strategies to address Travis’s negative self-perception. Travis particularly identified with the concept of challenging negative thoughts and created his own phrase, “Drop the negative and catch the positive.”

Family sessions focused on helping the family understand risk factors for relapse, including negative emotion in the home. In addition, the therapist focused on increasing positive communication strategies. This included use of praise, contingency management, and focusing on the patient’s strengths. The therapist collaborated with Travis and his family to develop a wellness plan that included enjoyable family activities, such as volunteering at the local food bank and weekly family game nights.

After 6 months, Travis’s symptoms of depression were in remission and remained in remission at week 30.

Conclusion

The literature on child and adolescent depression appears to support combination treatments in place of monotherapies. Future research needs to focus on how to use established treatments efficiently to optimize treatment gains. A promising strategy is to combine effective treatments sequentially to maximize their respective benefits. For example, antidepressants work quickly and effectively to reduce acute symptoms, whereas CBT appears to be effective in increasing the probability of remission and preventing relapse of depressive symptoms. Patients who have responded to antidepressant medication are likely to be more receptive and attentive to psychotherapeutic interventions. Thus, sequential treatment strategies are worth consideration in the treatment of pediatric depression.

References:

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