Benefits, Limitations, and Emerging Research Needs in Treating Youth with Depression
On February 6 and 7, 2006, experts in child and adolescent depression met in Washington, DC to review the state of the science of the treatment of youth depression and discuss approaches to further research. Participants included patient advocates and researchers in the fields of psychopharmacology, psychotherapies, clinical neuroscience, and clinical trial methodology and design. The main aims of the meeting were: a) to review the evidence for benefits and risks of existing treatment interventions for children and adolescents with depressive disorders; b) to identify important knowledge gaps in need of further research; and c) to discuss approaches to future research with respect to design, methods, and implementation.
Some of the issues considered were:
- Current evidence for the efficacy/effectiveness and benefit/risk ratio of existing treatment interventions for children and adolescents with depressive disorders
- How to individualize treatment
- How to address comorbidity
- How to address non-response and prevent relapse/recurrence
- Evidence on mechanisms of treatment action and specificity of response
- Influence of cultural and ethnic issues on treatment acceptability and effectiveness
- Effectiveness of treatments in practice settings
- Influence and limitation of the current nosology used for treatment development and testing
- How to develop novel, more effective treatment interventions
Conclusions and Future Considerations
- A number of interventions have been proven efficacious in the treatment of major depression in youth. These interventions include specific psychotherapies, such as cognitive-behavioral therapy and interpersonal therapy, pharmacotherapy with fluoxetine, and the combination of cognitive-behavioral therapy and fluoxetine.
- The overall balance between known treatment benefits and risks of these interventions is favorable.
- All patients in treatment for major depression require careful clinical monitoring for possible worsening of depressive symptoms, including suicidal ideation or behavior, and emergence of adverse effects.
- Now that efficacious treatments for depressed youth have been developed, research is needed to determine the optimal way of sequencing and combining interventions (including studies that address when polypharmacy is warranted and safe), maximizing resources, increasing efficiency, and effectively improving outcomes in practice.
- Even specific psychotherapies include multiple components (e.g., behavioral activation, cognitive restructuring, and interpersonal skill improvement). Research is needed to identify active ingredients of interventions and understand how treatment works. Better understanding of active ingredients of existing approaches may ultimately inform adaptations that are not only more potent but also potentially more efficient and transportable.
- Limited research has been conducted on treatment of depression in pre-pubertal children. Controlled clinical trials supporting the efficacy of fluoxetine exist, but more research is needed to develop and test effective pharmacological and psychosocial treatments for these children.
- Existing psychotherapeutic approaches are based largely on treatments initially developed for adults. Accordingly, many existing treatments may not be optimal for younger children. Alternative, developmentally sensitive approaches and novel treatments informed by emerging theories of developmental psychopathology should be explored.
- The current diagnostic construct of major depressive disorder is broad and subsumes diverse expressions of mood disturbance. Considerable heterogeneity exists among youths with major depression with respect to clinical phenomenology, treatment response, and outcomes. The development of more effective interventions is dependent on identifying narrower phenotypes with greater clinical validity that can be used as treatment targets. For example, advanced imaging techniques are being studied to improve our understanding of the pathophysiology of depression in youth and the effects of treatment on the brain. Research of this kind may contribute to better depression subtyping.
- Research approaches to individualizing treatment are needed. Evidence suggests that a subset of depressed youth do not respond fully to pharmacotherapy or psychotherapy, and conversely, another subset may respond quickly to minimal intervention. Studies that examine moderators of outcome (e.g., illness history, patient preference) and mechanisms of response may inform intervention adaptations and alternative approaches to treatment for non-responding youth.
- Results of selected studies and meta-analyses suggest that depression treatment effects may generalize to anxiety disorders. In general, the impact of comorbidity on depression treatment outcomes and strategies for addressing comorbid conditions in the context of depression treatment have received limited research attention.
- There is some evidence that treatment effects are maintained over follow-up periods of up to two years, but in general, few studies have examined long-term treatment outcomes. Even less is known about the potential value of continuation or maintenance treatment for preventing relapse or recurrence.
- Efforts at developing and testing interventions should be guided by an understanding of typical patients, providers, and service settings, including mental health specialty clinics and other settings where youth receive services (e.g., primary care, schools). Accordingly, practice-based trials and research that examines alternative service delivery models (e.g., collaborative-care models, approaches that incorporate patient preference) may yield results with the capacity to quickly impact the quality of "real world" depression care. International comparisons of pharmacoepidemiological data and service structures may also facilitate the identification of effective practices.