Impact of treatments for depression on comorbid anxiety, attentional, and behavioral symptoms in adolescents with selective serotonin reuptake inhibitor-resistant depression

Abstract

Objective: To assess the relative efficacy of antidepressant medication, alone and in combination with cognitive behavioral therapy (CBT), on comorbid symptoms of anxiety, attention, and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial.

Method: Adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression (N = 334) were randomly assigned to a medication switch alone (to another SSRI or to venlafaxine) or to a medication switch plus CBT. Anxiety, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks. The differential effects of medication and of CBT, and the impact of remission on the course of comorbid symptoms and diagnoses, were assessed using generalized linear mixed models.

Results: Remission was associated with a greater reduction in scalar measures of anxiety, ADHD, and DBDs, and a greater decrease in the rate of diagnosed anxiety disorders. The correlations between the changes in symptoms of depression on the CDRS-R and anxiety, ADHD, and oppositional symptoms were modest, ranging from r = 0.12 to r = 0.28. There were no significant differential treatment effects on diagnoses, or corresponding symptoms.

Conclusion: The achievement of remission had a beneficial effect on anxiety, ADHD, and DBD symptoms, regardless of the type of treatment received. There were no differential effects of medication or CBT on outcome, except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine. Clinical trial registration information-Treatment of SSRI-Resistant Depression In Adolescents (TORDIA); https://ichgcp.net/clinical-trials-registry/NCT00018902" title="See in ClinicalTrials.gov">NCT00018902.

Conflict of interest statement

Drs. Clarke, Ryan, and Shamseddeen, and Messrs. Hilton, Rengasamy, and Mansoor, and Mss. He, Mayes, and Porta report no biomedical financial interests or potential conflicts of interest.

Copyright © 2013. Published by Elsevier Inc.

Figures

FIGURE 1

Rates of anxiety, attention-deficit/ hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) diagnoses over time. Note: CBT = cognitive behavioral therapy; SSRI = selective serotonin reuptake inhibitor; VLX = venlafaxine.

FIGURE 2

Anxiety symptoms Screen for Child Anxiety Related Emotional Disorders (SCARED) and treatment. Note: a) Medication: β = −0.53, SE = 0.72, z = −0.74, p = .46; Time: β = −4.19, SE − 0.42, z = −10.01. p < .001; Interaction: β = 1.00, SE − 0.60, z = 1.67, p= .09. b) CBT: β = −0.36, SE = 0.72, z = −0.50, p= .62; Time: β = −3.95, SE = 0.42, z = −9.48, p < .001; Interaction: β = 0.53, SE = 0.60, z = 0.88, p= .38. CBT = cognitive behavioral therapy; SSRI = selective serotonin reuptake inhibitor.

FIGURE 3

Attention-deficit/hyperactivity disorder (ADHD) symptoms and treatment. Note: a) Medication: β = 0.08, SE = 0.07, z = 1.28, p = .20; Time: β = −0.08, SE = 0.02, z = −5.32, p < .001; Interaction: β = −0.02, SE = 0.02, z = − 1.11, p = .27. b) CBT: β = −0.04, SE = 0.07, z = −0.61, p = .54; Time: β = −0.10, SE = 0.01, z = −6.75, p < .001; Interaction: β = 0.01, SE = 0.02, z = 0.63, p = .53. CBT = cognitive behavioral therapy; SSRI = selective serotonin reuptake inhibitor.

FIGURE 4

Disruptive behavior disorder (DBD) symptoms and treatment. Note: a) Medication: β = 0.04, SE = 0.04, z = 0.80, p= .42; Time: β = −0.08, SE = 0.01, z =−7.52. p < .001; Interaction: β = −0.01, SE = 0.01, z = −0.65, p =51. b) CBT: β = 0.04, SE = 0.05, z = 0.97, p= .33; Time: β = −0.08, SE = 0.01, z = −7.88, p < .001; Interaction: β = −0.004, SE = 0.01, z = −0.32, p= .75. CBT = cognitive behavioral therapy; SSRI = selective serotonin reuptake inhibitor.

FIGURE 5

Impact of remission on symptoms. Note: a) Remission: β = 0.06, SE = 0.74, z = 0.08, p = .94; Time: β = −2.93, SE = 0.39, z = −7.52, p < .001; Interaction: β = −1.77, SE = 0.59, z = −2.97, p= .003. b) Remission: β = 0.04, SE = 0.07, z = 0.56, p = .58; Time: β = −0.06, SE = 0.01, z = −4.70, p < .001; Interaction: β = −0.07, SE = 0.02, z = −3.18, p= .001. c) Remission: β = 0.007, SE = 0.05, z = 0.16, p= .87; Time: β = −0.07, SE = 0.01, z = −7.27, p < .001; Interaction: β = −0.03, SE = 0.02, z= −1.98, p= .048. ADHD = attention-deficit/hyperactivity disorder; DBD = disruptive behavior disorder.