Long-Term Outcome of Adolescent Depression Initially Resistant to Selective Serotonin Reuptake Inhibitor Treatment: A Follow-Up Study of the TORDIA Sample

Division of Services and Intervention Research, National Institute of Mental Health, Room 7147, 6001 Executive Blvd, Bethesda, MD 20892-9633, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 11/2010; 72(3):388-96. DOI: 10.4088/JCP.09m05885blu
Source: PubMed


We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while nonresponders were given open treatment.
For the current study, patients were reassessed 48 (n = 116) and 72 (n = 130) weeks from intake. Data were gathered from February 2001 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology, and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE]), and relapse, as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed-effects regression models were applied to estimate remission, relapse, and functional recovery.
By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (P < .03). Participants with more severe depression, greater dysfunction, and alcohol or drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment (P < .001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year.
While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment. Identifier: NCT00018902.

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Available from: Joan Asarnow
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    • "Major depressive disorder (MDD) frequently presents in adolescence and is often recalcitrant to treatment (Brent, 2009) which leads to substantial morbidity, mortality, and a societal financial burden (Blazer et al., 1994; Greenberg et al., 2015). Suicide is a leading cause of death in adolescents and a stark reminder that the current mechanistic understanding of depression is underdeveloped (Vitiello et al., 2011). Unfortunately, antidepressant medications, cognitive-behavioral therapy, and combined treatment are either ineffective or have minimal durability for most depressed adolescents (March et al., 2009). "
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    • "The rate of response was also shown to be critical in adolescents in the treatment of serotonin-selective reuptake inhibitor (SSRI)-resistant depression in adolescents study. Individuals who respond early (first 6 weeks of treatment) are more likely to achieve full remission (Emslie et al. 2010; Vitiello et al. 2011). Even among responders, residual symptoms are common. "
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    • "Further, the persistence of residual symptoms puts patients at higher risk of relapse (Brent et al. 2001; Emslie et al. 2010). Sleep disturbance is the most common residual symptom in adolescent depression in responders who failed to remit in the acute phase treatment (Kennard et al. 2006; Vitiello et al. 2011). "
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