Age of Methylphenidate Treatment Initiation in Children With ADHD and Later Substance Abuse: Prospective Follow-Up Into Adulthood

Abstract

Objective-Animal studies report that age at stimulant exposure is positively related to later drug sensitivity. This study was designed to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to subsequent development of substance use disorder (SUD).Method-Prospective longitudinal study of 176 methylphenidate-treated white boys (6-12 years) with ADHD but without conduct disorder, evaluated at mean ages 18 (94% retention) and 25 (85%), and 178 comparisons diagnosed by blinded clinicians. The Cox proportional hazards model included childhood predictor variables: age at initiation of methylphenidate treatment, total cumulative dose, treatment duration; IQ; severity of hyperactivity; socioeconomic status; also lifetime parent mental disorder. Separate models tested for four lifetime outcomes: Any SUD, Alcohol SUD, Non-Alcohol SUD, and Stimulant SUD. Other outcomes included antisocial personality disorder, mood and anxiety disorders.

Attention-Deficit/Hyperactivity Disorder and Risk for Substance Use Disorders in Relatives

“…Although many epidemiological studies seem to find no or possibly even protective, effects of ADHD medication on SUD (17,18), there are still some lingering concerns about harmful effects of stimulant treatment stemming primarily from findings of animal and imaging studies (19)(20)(21). The fear that stimulant ADHD treatment may put susceptible individuals at risk for future SUD might, in fact, result in the withholding of effective pharmacological treatment in these individuals (22).…”

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats

“…In other words, a significant fraction of children and adolescent are concurrently or, more likely, sequentially exposed to stimulants and ethanol and more information is needed on how repeated exposure to the former drugs affect the initiation of ethanol intake and preference (Mannuzza et al., 2008). Specifically, treatment with stimulants begins at around age 9–11 (Mannuzza et al., 2008), approximately, whereas age of ethanol initiation (i.e., first intake of a full standard drink) takes place between 14 and 16 years of age (Pilatti et al., 2017).…”

“…Specifically, treatment with stimulants begins at around age 9–11 (Mannuzza et al., 2008), approximately, whereas age of ethanol initiation (i.e., first intake of a full standard drink) takes place between 14 and 16 years of age (Pilatti et al., 2017). …”

“…Animal studies suggest that repeated stimulant exposure may sensitize the neural and behavioral response to subsequent drug challenges, enhancing the reinforcing effects of these drugs and rendering the individual at risk for drug addiction (Mannuzza et al., 2008; Schenk & Davidson, 1998). The sensitization induced by drugs of abuse, which is thought to reflect the transition from a nonaddicted to an addicted state, can occur at many levels, yet it has been most often analyzed by assessing the progressive increase in drug‐induced motor stimulation that results from repeated drug exposure (Camarini & Pautassi, 2016).…”

Adolescent d -amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects during adolescence and cocaine abuse risk during adulthood

“…Some evidence that ADHD medication initiation (methylphenidate in particular) during adolescence may have different long-term consequences for adult SUD than initiation in childhood is derived from research specifically analyzing age of treatment onset. The older the child is when ADHD medication is initiated, the greater the risk of developing SUD in adulthood [4,[16][17][18]. Currently, there are no well-controlled studies on medication initiation after age 13 in individuals with ADHD.…”