Predictors of Treatment Response in Adolescent Depression
Often, depression in adolescents goes undiagnosed, and is therefore undertreated. Even when treatment is provided, remission rates are frequently between 30 and 40 percent. Adolescents who continue to suffer from depression perform poorly in school, begin to show signs of suicidal ideation and behaviors, and are more likely to form substance abuse dependence. Researchers have found that in order to successfully treat an adolescent’s depression, treatment must begin soon after the onset of symptoms, and such treatment must be tailored specifically to the individual adolescent’s needs. Each adolescent is different; some only require medicine for improvement, others respond well to therapy, and yet another few will need the assistance of both to see symptom improvements.1 Pinpointing the characteristics that will respond successfully to certain treatments was the focus of three large-scaled studies: Treatment for Adolescents with Depression Study (TADS), Treatment for SSRI-Resistant Depression in Adolescents (TORDIA), and Adolescent Depression Antidepressant and Psychotherapy Trial (ADAPT). These three studies focused on demographic, illness, and family characteristics, as well as co-occurring disorders and treatment courses.1
All three studies examined the effectiveness of medicine and/or cognitive behavioral therapy (CBT) in patients suffering from moderate to severe depression, including those who had suicidal ideation or behaviors.1 The TADS study included 439 participants, aged 12 to 17 years. In order to qualify for the study, participants had to have previously suffered six weeks of depressed mood.4 If so, they were assigned to one of four groups: fluoxetine, CBT, both fluoxetine and CBT, or placebo.4 The TORDIA study included 334 participants, aged 12 to 18 years, who had failed to respond to previous treatment for depression. Participants were assigned to one of four groups: selective serotonin reuptake inhibitor (SSRI), SSRI plus CBT, venlafaxine, or venlafaxine plus CBT.5 The ADAPT study included 208 participants, aged 11 to 17 years, who also had failed to respond to previous treatment for depression. Participants were assigned to one of two groups: SSRI or SSRI plus CBT.6
Overall, the studies differed with their primary and demographic findings. The TADS study reported that medicine alone or medicine plus CBT proved to be the most effective methods of treatment during the first 12 weeks of the study; however, by week 18, CBT alone had also begun to show results that were just as effective.1 The TORDIA study found that SSRI plus CBT was a more effective method of treatment compared to SSRI alone.5 Conversely, the ADAPT study reported that there was no difference in the effectiveness of the SSRI only or SSRI plus CBT treatment methods.6 Age-wise, the TADS study reported adolescents 15 years and younger had better outcomes during the study, while the TORDIA study found that adolescents 18 and 19 years had better overall outcomes. Also, the TADS study found that while gender did not have an effect on treatment initially, follow-up data showed that females were more likely to relapse than males.
Regarding the participants’ depression characteristics, both severity of depression and presence of suicidal ideation or behaviors affected the overall treatment outcome for the patient.1 The studies found that participants who suffered from severe depression were more likely to respond poorly to treatment and participants with moderate depression responded well to medicine plus CBT treatment.1 TADS reported that participants who suffered from moderate depression responded well to medicine plus CBT, while those who suffered from severe depression did not respond well to the addition of CBT to their therapy.4 TORDIA also reported that patients suffering from moderate depression responded well to medicine plus CBT; however, TORDIA found that those with severe depression did as well.7 Also, TORDIA participants who did not experience suicidal ideation/behavior were more likely to show improved depression symptoms after 12 weeks.8 ADAPT reported that 34 percent of patients with suicidal ideation/behaviors at the beginning of the study continued to suffer from depression after 28 weeks, while only 10 percent of those who did not initially show suicidal ideation/behaviors continued to suffer.8 Therefore, participants with mild depression and of younger age will respond well to CBT alone, while participants with severe depression and of an older age will benefit from a more aggressive treatment, and will only benefit from CBT when medicine has initially improved their symptoms.
The three studies reported that participants who experienced co-occurring psychiatric disorders, aside from disruptive disorders such as ADHD, had poorer treatment outcomes.1 The majority of participants with co-occurring disorders suffered from depression and anxiety, and TADS and ADAPT reported those participants did not show an equal improvement in depression symptoms as those who did not suffer from a co-occurring anxiety disorder.8 Also, ADAPT reported that participants with co-occurring obsessive-compulsive disorders showed the same results. However, the studies did find that adding CBT to medicine therapy did improve participants’ outcomes, when suffering from a co-occurring disorder.1
Levels of family stress and history of abuse and trauma also affected patients’ treatment success. TADS and TORDIA reported that higher levels of family stress and conflict was associated with poorer treatment outcomes, and participants who experienced better family communication, more family involvement, and agreed with family rules and values responded well to medicine plus CBT therapy.7 Regarding history of abuse and trauma, TADS reported that patients who had experienced either responded well to both medicine alone or medicine plus CBT.1 They did not respond well to CBT alone, as the CBT for all three studies was focused around depression and not trauma or abuse.
Overall, the studies revealed that certain characteristic changes by week 12 of treatment can predict whether the patient will experience a relapse of depression or make a recovery.1 Both TADS and TORDIA found that patients who showed less symptoms of depression by week 12 were more likely to make a recovery.1 However, TORDIA also reported that a decrease in characteristics such as hopelessness, suicidal ideation, anxiety, and family conflict by week 12 also foreshadowed patient recovery.3
 Emslie, G.J.; Kennard, B.D.; Mayes, T.L. (2011). Predictors of Treatment Response in Adolescent Depression. Psych Annals 41(4): 213-219.
 Birmaher, B.; Brent, D.A.; AACAP Work Group on Quality Issues, et al (2007). Practice Parameter for the Assessment and Treatment of Children and Adolescents with Depressive Disorder. J Am Acad Child Adolesc Psychiatry 46(11): 1503-1526.
 Emslie, G.J.; Mayes, T.L.; Porta, G.; et al (2010). Treatment of Resistant Depression in Adolescents: Week 24 Outcomes. Am J Psychiatry 167(7): 782-791.
 March, J.; Silva, S.; Petrycki, S.; et al (2004). Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents with Depression: Treatment for Adolescents with Depression Study. JAMA 292(7): 807-820.
 Brent, D.; Emslie, G.; Clarke, G.; et al (2008). Switching to Another SSRI or to Venlafaxine with or without Cognitive Behavioral Therapy for Adolescents with SSRI-Resistant Depression: the TORDIA Randomized Controlled Trial. JAMA 299(8): 901-913.
 Goodyer, I.M.; Dubicka, B.; Wilkinson, P.; et al (2007). Selective Serotonin Reuptake Inhibitors (SSRIs) and Routine Specialists Care with and without Cognitive Behavior Therapy in Adolescents with Major Depression: randomized controlled trial. BMJ 335(7611): 142.
 Asamow, J.R.; Emslie, G.J.; Clarke, G.; et al (2009). Treatment of Selective Serotonin Reuptake Inhibitor Resistant Depression in Adolescents: Predictors and Moderators of Treatment Response. J Am Acad Child Adolesc Psychiatry 48(3): 330-339.
 Curry, J.; Silva, S.; Rohde, P.; Ginsburg, G.; et al (2011). Recovery and Recurrence Following Treatment for Adolescent Major Depression. Arch Gen Psychiatry 68(3): 263-269.
 Wilkinson, P.; Dubicka, B.; Kelvin, R.; Roberts, C.; and Goodyer, I. (2009). Treated Depression in Adolescents: Predictors of Outcome at 28 Weeks. Br J Psychiatry 194(4): 334-341.