05. Impact of Pharmacotherapy of Childhood-Onset Psychiatric Disorders on the Development of Substance Use Disorders

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Hi! David Rosenberg here for the Psychopharmacology Institute. In this CAP or Child and Adolescent Psychiatry Smart Take, we will take a closer look at whether or not pharmacotherapy of childhood-onset psychiatric disorders increases the risk of future substance use and substance use disorders. In this comprehensive meta-analysis conducted by the Massachusetts General Hospital team, Dr. Wilens and colleagues do a deep dive critically examining 26 prior longer-term studies, which included 21 studies of patients with ADHD, 2 in pediatric major depressive disorder (MDD), and 3 on psychosis, which translated into about 6 million patients included in their analysis. So, this is a comprehensive and well-done informative paper for clinicians practicing in the trenches with real-world significance.

So, what did they find, and what are the key take-home points? Not only does pharmacotherapy for ADHD and MDD in childhood and adolescence not increase the risk of substance use or substance misuse or substance use disorder, but there was also a striking and significant reduction in the risk of developing substance use disorders by 30% or more. This effect was most significant when pharmacotherapy was initiated earlier and continued for longer. There was also a signal suggesting a reduction in the risk of developing substance use disorders with medication treatment of bipolar disorder and psychosis in youth. The most pronounced reduction was seen in patients with ADHD. This is a significant finding given the concern often voiced about the potentially addictive effects of ADHD treatment, particularly stimulant medications. This well-done study with a large sample strongly suggests that when stimulants and other medications are used for the appropriate indication and dose, the risk for future substance use disorder is not increased; it significantly decreases. This makes sense when we look at the symptomatology of ADHD. Effective treatment may improve impulse control and other symptoms that could increase the risk of disinhibition, substance use, and the eventual emergence of substance use disorder—so, very promising.

However, there are some caveats to consider. For ADHD, stimulants are often the treatment of choice, but even with evidence suggesting a reduced risk for subsequent development of substance use disorders, caution is needed, particularly in some high-risk populations. So, I am always very cautious about using stimulants in ADHD patients with a comorbid substance use disorder. The risk increases, and it is unclear whether stimulants are as effective in that population as in children and adolescents with a first-degree relative—a parent or a sibling—who has comorbid substance use or significant substance use disorders. I am inclined to avoid stimulants in most cases because these are high-risk populations and nonstimulant alternatives are often preferable.

Now, with the extended-release preparations of methylphenidate and amphetamine, the risk of abuse is decreased. However, we have all heard about people, particularly with immediate-release stimulants, misusing them to do better on an examination. I have been called by friends and others in the community, asking if I would be willing to prescribe methylphenidate for a son or daughter who is taking a big test, like the SAT for college, and, of course, that is entirely inappropriate. What I always say is that I would be pleased to do an evaluation and see whether a medication is indicated. Accurate diagnoses are the best predictor of good treatment response; many of these conditions are associated with comorbid conditions, which often take longitudinal assessments. Nevertheless, an accurate diagnosis is the best predictor of a good treatment outcome.

This analysis has some limitations—mainly that comorbidity was not addressed, and we know that ADHD, MDD, and psychosis are highly comorbid conditions. So, this is important. The analysis also did not focus on psychotherapies, often used in treating these conditions. They did not look at psychotherapy-only treatments nor did they examine medication plus psychotherapy, which, at least for some conditions, is the most likely to result in symptom reduction and even symptom remission compared with medication alone or psychotherapy alone.

The bottom line is that this is an excellent, clinically relevant study with immediate implications for those of us practicing and seeing patients in the trenches. It appears that pharmacotherapy and childhood-onset psychiatric disorders do not increase the likelihood of substance use, misuse, or substance use disorder and may significantly reduce this risk, especially when medication is initiated early and for a longer duration. So, a fascinating, meaningful, and understudied area, directly applicable to practicing clinicians, with important information for us to disseminate among our fellow clinicians, patients, and their families.

Abstract

The Impact of Pharmacotherapy of Childhood-Onset Psychiatric Disorders on the Development of Substance Use Disorders

Timothy E Wilens, Diana W Woodward, Je Deuk Ko, Amy F Berger, Colin Burke, Amy M Yule

Background and Objective: Child- and adolescent-onset psychopathology is known to increase the risk for developing substance use and substance use disorders (SUDs). While pharmacotherapy is effective in treating pediatric psychiatric disorders, the impact of medication on the ultimate risk to develop SUDs in these youth remains unclear. Methods: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of peer-reviewed literature published on PubMed through November 2021, examining pharmacological treatments of psychiatric disorders in adolescents and young adults and their effect on substance use, misuse, and use disorder development. Results: Our search terms yielded 21 studies examining the impact of pharmacotherapy and later SUD in attention-deficit/hyperactivity disorder (ADHD), two studies on Major Depressive Disorder, and three studies on psychotic disorders. The majority of these studies reported reductions in SUD (N = 14 sides) followed by no effects (N = 10) and enhanced rates of SUD (N = 2). Studies in ADHD also reported that earlier-onset and longer-duration treatment was associated with the largest risk reduction for later SUD. Conclusions: Overall, pharmacological treatments for psychiatric disorders appear to mitigate the development of SUD, especially when treatment is initiated early and for longer durations. More studies on the development of SUD linked to the effects of psychotherapy alone and in combination with medication, medication initiation and duration, adequacy of treatment, non-ADHD disorders, and psychiatric comorbidity are necessary.

Reference

Wilens, T. E., Woodward, D. W., Ko, J. D., Berger, A. F., Burke, C., & Yule, A. M. (2022). The impact of pharmacotherapy of childhood-onset psychiatric disorders on the development of substance use disorders. Journal of Child and Adolescent Psychopharmacology, 32(4), 200-214.