01. Relapse Prevention Strategies for Depression and Anxiety in Remitted Youth

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Hi! David Rosenberg here for the Psychopharmacology Institute. In this CAP, or Child and Adolescent Psychiatry Smart Take, we will examine depression and anxiety in remitted adolescents and young adults. Additionally, we will focus on the effectiveness of relapse prevention strategies concerning the risk of and time to relapse. Relapse rates for youth with major depressive disorder are high, ranging from 50%–70% during a 6-month to 2-year follow-up and surpassing 70% in a 15-year follow-up.

Anxiety and depression during youth strongly predict depression and anxiety in adulthood. These conditions are frequently comorbid; each elevates the risk of the other. However, there has been a limited focus on effective relapse prevention strategies for remitted youth with these disorders. The most prevalent interventions are continuation of antidepressant medication; psychological interventions, like cognitive–behavioral therapy (CBT); or a combination of both. This research conducts the first meta-analysis and systematic review of relapse strategies. It includes antidepressant continuation, psychological interventions, or their combination for remitted youth aged 13–25 with major depressive disorder or anxiety disorders. These strategies are compared with control conditions concerning relapse rate, time to relapse, and symptom severity.

The findings indicate that 9 randomized controlled trials existed for youth with major depressive disorder. However, none were identified for anxiety relapse. For depression relapse, CBT-based treatment, either alone or combined with antidepressant continuation, resulted in half the likelihood of relapse, an extended time to relapse, and notably reduced depressive symptoms at the final follow-up vs control conditions (i.e., typical treatment, pill placebo, or absence of antidepressant continuation). Despite this, relapse rates remained high: 52% for CBT alone and 42% when combined with antidepressants. Time to relapse was longer, and relapse was less probable in youth receiving antidepressants compared with a pill placebo over a 6–12 month follow-up. Yet, relapse rates were elevated in both groups: 42% for those on antidepressants and 67% for control conditions.

It is crucial to note the significant difference in relapse rates: 67% in control conditions vs 42% in the antidepressant group. This underscores the advantage of continuation treatment. Yet, the 42% relapse rate in the antidepressant group is still noteworthy. It aligns with current knowledge on major depressive disorder—treatment can be beneficial, but there’s room for improvement. Even with effective treatment continuation, relapse risk remains, albeit reduced. The longest time to relapse occurred when CBT and antidepressants were combined. This supports the growing consensus that combining CBT and antidepressant treatment offers the most symptom reduction. Furthermore, continuing both treatments may reduce relapse risk or at the least delay its onset.

In conclusion, relapse prevention strategies can decrease the relapse risk for major depressive disorder in youth by approximately 50%. However, these are group findings and cannot be individualized. Combining CBT with antidepressant continuation shows the highest potential for reducing relapse likelihood, time to relapse, and depressive symptoms in youth. Regrettably, no studies investigated relapse strategies for youth with anxiety disorders, highlighting a significant gap in research.

Abstract

Objective: Depression and anxiety cause a high burden of disease and have high relapse rates (39%-72%). This meta-analysis systematically examined effectiveness of relapse prevention strategies on risk of and time to relapse in youth who remitted.

Method: PubMed, PsycInfo, Embase, Cochrane, and ERIC databases were searched up to June 15, 2021. Eligible studies compared relapse prevention strategies to control conditions among youth (mean age 13-25 years) who were previously depressed or anxious or with ≥30% improvement in symptoms. Two reviewers independently assessed titles, abstracts, and full texts; extracted study data; and assessed risk of bias and overall strength of evidence. Random-effects models were used to pool results, and mixed-effects models were used for subgroup analyses. Main outcome was relapse rate at last follow-up (PROSPERO ID: CRD42020149326).

Results: Of 10 randomized controlled trials (RCTs) that examined depression, 9 were eligible for analysis: 4 included psychological interventions (n = 370), 3 included antidepressants (n = 80), and 2 included combinations (n = 132). No RCTs for anxiety were identified. Over 6 to 75 months, relapse was half as likely following psychological treatment compared with care as usual conditions (k = 6; odds ratio 0.56, 95% CI 0.31 to 1.00). Sensitivity analyses including only studies with ≥50 participants (k = 3), showed similar results. Over 6 to 12 months, relapse was less likely in youth receiving antidepressants compared with youth receiving pill placebo (k = 3; OR 0.29, 95% CI 0.10 to 0.82). Quality of studies was suboptimal.

Conclusion: Relapse prevention strategies for youth depression reduce risk of relapse, although adequately powered, high-quality RCTs are needed. This finding, together with the lack of RCTs on anxiety, underscores the need to examine relapse prevention in youth facing these common mental health conditions.

Keywords: anxiety disorders; depressive disorders; intervention; meta-analysis; relapse prevention.

Reference

Robberegt, S. J., Brouwer, M. E., Kooiman, B. E. A. M., Stikkelbroek, Y. A. J., Nauta, M. H., & Bockting, C. L. H. (2023). Meta-analysis: Relapse prevention strategies for depression and anxiety in remitted adolescents and young adults. Journal of the American Academy of Child and Adolescent Psychiatry, 62(3), 306-317.