Chapter 42: ADHD – Stimulant & Nonstimulant Drug Therapy

Attention Deficit Hyperactivity Disorder (ADHD) is a widespread neurodevelopmental condition stemming from complex biopsychosocial factors, often lasting into adulthood, characterized by clinically significant impairments in attention, impulsivity, and/or hyperactivity that disrupt academic, social, or occupational functioning. Its pathophysiology involves diminished volume and activity in key brain regions like the prefrontal cortex, caudate, and cerebellum, which are crucial for executive functions, emotion regulation, and attention. These areas rely on the balanced interaction of the neurotransmitters dopamine and norepinephrine. Diagnosing ADHD utilizes criteria from the DSM-5, requiring a persistent pattern of symptoms (at least six for children/adolescents or five for adults aged 17 and older) present in multiple settings and causing clear functional impairment, with symptom onset required before age 12. Diagnosis can be complicated in adults due to recall bias and the development of sophisticated compensatory mechanisms used to mask or overcome functional deficits. Since ADHD is frequently comorbid with other psychiatric disorders, such as anxiety, depression, and Substance Use Disorders (SUDs), assessment for these coexisting conditions is mandatory. Treatment generally follows a multimodal plan combining behavioral interventions with pharmacotherapy. Stimulant medications, derived from methylphenidate or amphetamine, are the established first-line treatment for all ages, primarily due to their superior efficacy and rapid onset of action, working by blocking the reuptake of dopamine and norepinephrine. Extended-release stimulant formulations are preferred for their convenience, improved compliance, and reduced risk of abuse, especially prodrug options like lisdexamfetamine. If stimulants are clinically ineffective, intolerable, or contraindicated (such as in patients with active SUDs or cardiovascular disease), second-line therapy is the nonstimulant atomoxetine, which targets norepinephrine reuptake and poses no risk of abuse. Third-line options include bupropion, often chosen for patients with comorbid depression or SUD history, and alpha-2 agonists (guanfacine, clonidine), which are primarily utilized for behavioral manifestations, aggression, or tics. Consistent monitoring of efficacy and adverse effects, particularly cardiovascular changes and growth in children, is critical throughout the treatment course.