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<p>Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition characterized by persistent difficulties with attention, impulsivity, and hyperactivity, manifesting primarily in inattentive, hyperactive-impulsive, or combined forms. Clinical observations and extensive research indicate that individuals with the combined subtype (ADHD-C), characterized by marked hyperactivity and impulsivity, exhibit a significantly higher susceptibility to substance abuse and addiction-related problems compared to those with predominantly inattentive ADHD (ADHD-I) (Wilens, 2011; Lee et al., JAMA Psychiatry 68:936–944,2011). This article examines the hypothesis that this increased vulnerability in ADHD-C is linked to increased activity within the mesolimbic dopamine pathways, specifically the nucleus accumbens (NAc) and amygdala, in response to central stimulant (CS) treatment. Existing neuroimaging studies, including work by Costa Dias et al. (Psychiatry Res: Neuroimaging 214:257–265,2013) and Plichta and Scheres (Curr Psychiatry Rep 16:451,2014), consistently demonstrate excessive activation of the NAc during reward anticipation in patients with ADHD-C, which strongly correlates with impulsivity and increased risk-taking behavior. In addition, Volkow (JAMA 302:1084–1091,2009; Neuropsychopharmacology 34:3-6,2009) points out that central stimulants such as methylphenidate and amphetamine derivatives can exacerbate this dopaminergic dysregulation, especially when administered in high doses or in fast-acting formulations. Conversely, patients diagnosed with ADHD-I typically show hypoactivation of the prefrontal cortex and reduced baseline activity in reward-processing regions, including the NAc (Volkow et al., JAMA 302:1084–1091,2009; Volkow et al., Neuropsychopharmacology 34:3-6,2009; Shaw et al.,Am J Psychiatry 171:276–93,2014). Accordingly, stimulant treatment in ADHD-I generally improves dopaminergic function without inducing significant impulsivity, substance abuse risk, or reinforcement-seeking behaviors, underscoring critical neurobiological distinctions between the subtypes. This article, based on a meta-analytic review, systematically evaluates how different responses to stimulant treatment across ADHD subtypes affect relapse rates into addictive behaviors. The analysis underscores a tailored, subtype-by-impulsivity-level treatment approach, suggesting that individuals with ADHD-C—particularly those who exhibit pronounced impulsivity, emotional dysregulation, and a history of drug use—may more safely benefit from carefully monitored stimulant regimens, alternative pharmacological interventions such as atomic or adjunctive therapy, guanfacine therapy, and treatment aimed for emotional regulation and inhibitory control. Evidence suggests that ADHD-C individuals are more vulnerable to stimulant-induced relapse due to mesolimbic dopaminergic hypersensitivity. This review aims to inform safer pharmacological choices based on neurobiological subtype. This individualized approach emphasizes understanding and adjusting for distinct neurobiological profiles, ultimately guiding more effective, personalized treatments for ADHD, thereby reducing the risks associated with addiction and improving overall treatment outcomes.</p>

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Tailoring strategies to the type and level of impulsivity: subtype-by-impulsivity level individualized treatment approach for ADHD

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月19日

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  • Davoud Amiri,
  • Lamberto Briziarelli,
  • Elaheh Rasekhian

摘要

Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition characterized by persistent difficulties with attention, impulsivity, and hyperactivity, manifesting primarily in inattentive, hyperactive-impulsive, or combined forms. Clinical observations and extensive research indicate that individuals with the combined subtype (ADHD-C), characterized by marked hyperactivity and impulsivity, exhibit a significantly higher susceptibility to substance abuse and addiction-related problems compared to those with predominantly inattentive ADHD (ADHD-I) (Wilens, 2011; Lee et al., JAMA Psychiatry 68:936–944,2011). This article examines the hypothesis that this increased vulnerability in ADHD-C is linked to increased activity within the mesolimbic dopamine pathways, specifically the nucleus accumbens (NAc) and amygdala, in response to central stimulant (CS) treatment. Existing neuroimaging studies, including work by Costa Dias et al. (Psychiatry Res: Neuroimaging 214:257–265,2013) and Plichta and Scheres (Curr Psychiatry Rep 16:451,2014), consistently demonstrate excessive activation of the NAc during reward anticipation in patients with ADHD-C, which strongly correlates with impulsivity and increased risk-taking behavior. In addition, Volkow (JAMA 302:1084–1091,2009; Neuropsychopharmacology 34:3-6,2009) points out that central stimulants such as methylphenidate and amphetamine derivatives can exacerbate this dopaminergic dysregulation, especially when administered in high doses or in fast-acting formulations. Conversely, patients diagnosed with ADHD-I typically show hypoactivation of the prefrontal cortex and reduced baseline activity in reward-processing regions, including the NAc (Volkow et al., JAMA 302:1084–1091,2009; Volkow et al., Neuropsychopharmacology 34:3-6,2009; Shaw et al.,Am J Psychiatry 171:276–93,2014). Accordingly, stimulant treatment in ADHD-I generally improves dopaminergic function without inducing significant impulsivity, substance abuse risk, or reinforcement-seeking behaviors, underscoring critical neurobiological distinctions between the subtypes. This article, based on a meta-analytic review, systematically evaluates how different responses to stimulant treatment across ADHD subtypes affect relapse rates into addictive behaviors. The analysis underscores a tailored, subtype-by-impulsivity-level treatment approach, suggesting that individuals with ADHD-C—particularly those who exhibit pronounced impulsivity, emotional dysregulation, and a history of drug use—may more safely benefit from carefully monitored stimulant regimens, alternative pharmacological interventions such as atomic or adjunctive therapy, guanfacine therapy, and treatment aimed for emotional regulation and inhibitory control. Evidence suggests that ADHD-C individuals are more vulnerable to stimulant-induced relapse due to mesolimbic dopaminergic hypersensitivity. This review aims to inform safer pharmacological choices based on neurobiological subtype. This individualized approach emphasizes understanding and adjusting for distinct neurobiological profiles, ultimately guiding more effective, personalized treatments for ADHD, thereby reducing the risks associated with addiction and improving overall treatment outcomes.