Casual Cannabis, Alcohol Use Reduces Treatment Efficacy in Adolescents With Major Depression

Caroline Cassels

October 30, 2009

October 30, 2009 (Honolulu, Hawaii) — Casual substance can significantly reduce the efficacy of antidepressant therapy in adolescents with treatment-resistant major depressive disorder (MDD) — a finding that suggests clinicians need to screen for — and intervene when they detect — any substance use in this at-risk population.

New research presented here at the American Academy of Child & Adolescent Psychiatry 56th Annual Meeting by investigators from the University of Pittsburgh, Pennsylvania, shows that subthreshold substance use is common and that low substance scores after 12 weeks of therapy were associated with better treatment response regardless of whether participants had high or low baseline substance-related impairment.

Dr. Benjamin Goldstein

"It was more important how much substance use kids were involved in at the end of the study than at study outset. So those who started off using and ended up not using had...[an] antidepressant response [that] was as good as anyone else's. But those who continued to use substances or who progressed to substance use during the study had a significantly lower treatment response," study investigator Benjamin I. Goldstein, MD, told Medscape Psychiatry.

These current findings are a substudy of the larger Treatment of Resistant Depression in Adolescents (TORDIA) study, which is examining comparing cognitive behavioral therapy with cognitive behavioral therapy in combination with selective serotonin reuptake inhibitor venlafaxine improves outcomes in adolescents with MDD who had failed to respond to a first trial with a selective serotonin reuptake inhibitor treatment.

Physician Ambivalence

Substance use disorders among adolescents with MDD have been associated with suicidality, poor treatment outcomes, legal difficulties, risky sexual behavior, and functional impairment. However, the researchers note that little is known about the effect of lower levels of substance use and treatment response in adolescents who do not meet criteria for substance abuse or dependence.

Dr. Goldstein said the substudy was also prompted by the ambivalence clinicians have with regard to recreational substance abuse with cannabis or alcohol.

"To a certain extent, it is developmentally appropriate for adolescents to experiment, and clinicians are often reluctant to intervene. But the risks of experimental substance use in adolescents with treatment-resistant MDD are not the same as the risks of cannabis or alcohol use for adolescents in general," said Dr. Goldstein.

The study included 334 adolescents with MDD who were assessed for substance use with the Drug Use and Severity Index in relation to treatment and depressive symptoms.

The investigators found that 28.1% of the participants reported repeated substance use experimentation with alcohol or cannabis at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder.

The study also showed that baseline suicidal ideation predicted increased substance-related impairment, and parental depressive symptoms predicted persistence of high substance-related impairment.

Clinically Noteworthy

"This study suggests that regardless of whether someone meets the criteria for substance abuse or dependence, substance use should be an area of clinical focus in these patients. As clinicians, we have to be more fine-tuned in our approach to substance use and understand that even recreational or social substance use is something that is clinically noteworthy and worth addressing directly with adolescents," said Dr. Goldstein.

Although the underlying mechanisms are not clear, it is possible that casual substance abuse has a direct effect on antidepressant therapy. Dr. Goldstein also speculated that youth who use substances may be more likely to have peers that do the same, and those peers may be less supportive of the adolescents' recovery.

Dr. Goldstein said further research is needed to examine the association of occasional substance use and longitudinal outcomes in this patient population. The researchers are also conducting analyses on 26-week data in this cohort.

American Academy of Child & Adolescent Psychiatry 56th Annual Meeting: Abstract 1.41. Presented October 26, 2009.

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