Treatment-Resistant Depression in Adolescents: Recognition and Management

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Treatment-resistant depression

The term “treatment-resistant depression” is defined to mean lack of response to adequate treatment. There is recognition that treatment resistance exists on a continuum as a function of the number and type of treatments one has received, but much of the extant literature refers to patients who fail to respond to even one adequate trial as treatment resistant [2], [3]. An adequate response in the clinical trial literature has been defined most often as “much” or “very much” improvement on the

Rates of treatment response in selective serotonin reuptake inhibitors and psychotherapy trials

Examining all clinical trials that involved SSRIs, the initial clinical response rate is approximately 60%, which means that approximately 40% of participants are partial- or nonresponders or would be defined as having treatment-resistant depression [23]. The rate of symptomatic remission (being symptom free) at 8 to 12 weeks is much lower—approximately 30% to 40% [24], [25]. Naturalistic treatment studies suggest that the proportion of patients who achieve clinical remission increases with

Demographics

Some studies have reported that younger children respond as well to SSRIs as adolescents [24], whereas other studies have shown a better response in adolescents than in children [33]. Adolescents also seem to metabolize SSRIs more rapidly than do adults, with much shorter steady-state half-lives found for paroxetine, sertraline, and citalopram [34], [35], [36]. Higher doses or twice-a-day dosing may be required for some adolescents. A second developmental difference compared with adults is the

Document improvement or the lack thereof

Patients who have been chronically depressed often have difficulty judging improvement unless assessment is anchored to concrete markers and symptoms, which is aided by the use of standardized assessments, such as the CDRS-R [5], or the self-report scales, such as the Children's Depression Inventory [67], Beck Depression Inventory [68], Mood and Feelings Questionnaire [69], [70], Center for Epidemiologic Studies-Depression Scale [71], and the Reynolds Adolescent Depression Scale [72]. A patient

Addressing co-occurring health risk behaviors and contextual factors

Several intercorrelated health risk behaviors that co-occur with depression often are not addressed or even assessed in typical clinical trials [63], [140], [141]. A frequently overlooked source of morbidity in depressed adolescents is persistent sleep difficulties. From a developmental point of view, the average adolescent needs more sleep and gets less sleep than younger children [142]. On top of this developmental sleep deficit, depressed adolescents have sleep disruption, and SSRIs can

Summary and recommendations for further research

How can we use this information to improve the outcome of depressed adolescents? First, for an optimal response, one must promote and ensure adherence and use an adequate dose of medication or psychotherapy given for an adequate duration. Psychoeducation that promotes parental and child hopefulness in the context of realistic expectation about treatment may be helpful in improving adherence, and outcome. Proper assessment of psychiatric and medical comorbidity and environmental factors

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    This work was supported by NIMH grants P30 MH66371 and U01 MH61835.

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