Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response

J Am Acad Child Adolesc Psychiatry. 2009 Mar;48(3):330-339. doi: 10.1097/chi.0b013e3181977476.

Abstract

Objective: To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies.

Method: Youths who had not improved during an adequate SSRI trial (N = 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response.

Results: Less severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy.

Conclusions: Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Chronic Disease
  • Cognitive Behavioral Therapy*
  • Combined Modality Therapy
  • Cyclohexanols / adverse effects
  • Cyclohexanols / therapeutic use*
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Drug Resistance
  • Female
  • Fluoxetine / adverse effects
  • Fluoxetine / therapeutic use
  • Humans
  • Male
  • Paroxetine / adverse effects
  • Paroxetine / therapeutic use
  • Personality Inventory
  • Prognosis
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Venlafaxine Hydrochloride

Substances

  • Antidepressive Agents, Second-Generation
  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Paroxetine
  • Venlafaxine Hydrochloride

Grants and funding