Pharmacotherapy interventions for adolescent co-occurring substance use and mental health disorders: a systematic review

Fam Pract. 2022 Mar 24;39(2):301-310. doi: 10.1093/fampra/cmab096.


Background: Co-occurring mental health and substance use (SU) disorders among adolescents are common, with two-thirds of adolescents who seek SU treatment also requiring support for mental health. Primary care physicians play a key role in the pharmacological treatment of mental health disorders among adolescents, however, little is known about the impact of these treatments on SU outcomes.

Objectives: This systematic review summarizes the evidence regarding commonly used pharmacotherapy interventions for mental health and their impact on adolescent SU.

Methods: Literature searches were conducted across five databases as part of a larger systematic review of adolescent SU interventions. Studies were screened for eligibility by two researchers, and study data were extracted regarding study design, patient and treatment characteristics and results. Risk of bias analyses and qualitative syntheses were completed to evaluate the strength of the evidence and the impact of pharmacotherapy on SU outcomes.

Results: Ten randomized controlled trials exploring seven pharmacotherapies met criteria for inclusion. All studies had low to moderate risk of bias. Four studies evaluated pharmacotherapy for co-occurring depression and SU, three evaluated attention deficit hyperactivity disorder and SU, and three evaluated bipolar disorder and SU. Five of the 10 studies also included a behavioural intervention. We found no evidence that pharmacotherapy for co-occurring mental health diagnoses impacted SU.

Conclusion: Family medicine clinicians prescribing pharmacotherapy for mental health should be aware that additional interventions will likely be needed to address co-occurring SU.

Keywords: adolescent medicine; co-occurring disorders; mental health; pharmacotherapy; substance use; systematic review.

Plain language summary

Many adolescents have both mental health and substance use problems. Adolescents have difficulty getting effective treatment for both substance use and mental health concerns, in part because these treatments are often offered separately. Primary care physicians, who often care for adolescents with mental health concerns, may prescribe medications for diagnoses such as attention deficit hyperactivity disorder, depression or early symptoms of bipolar disorder. However, there is little research indicating whether these medications are helpful for co-occurring substance use disorder symptoms. This paper presents a review of existing research on medications used to treat common mental health disorders to evaluate their effect on substance use. Ten studies address this question and suggest that medications for mental health are insufficient for helping adolescents with substance use disorders or substance use problems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Systematic Review

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity*
  • Behavior Therapy
  • Bipolar Disorder*
  • Humans
  • Mental Disorders* / complications
  • Mental Disorders* / drug therapy
  • Mental Health
  • Substance-Related Disorders* / drug therapy