Chapter 43: Substance Use Disorders – Treatment Pharmacology

Substance Use Disorders (SUDs) are defined by the recurrent use of drugs or alcohol leading to clinically significant impairment, representing a major public health concern that remains largely undertreated. Addiction, the severe form of SUD, is understood as a chronic brain disease rooted in the mesolimbic reward pathway, where substances disrupt the normal dopaminergic signaling from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Diagnosis is established using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, requiring a patient to exhibit at least two of eleven criteria to determine mild, moderate, or severe disorder. Effective management utilizes the evidence-based Screening, Brief Intervention, and Referral to Treatment (SBIRT) approach, employing tools like the AUDIT or DAST-10 to assess severity and identify the appropriate intervention level. Treatment programs share generalized goals: reducing substance use, improving overall life functioning, and minimizing the frequency and severity of relapse, with total abstinence being linked to the best long-term outcomes. For Alcohol Use Disorder (AUD), acute withdrawal—which can progress to life-threatening delirium tremens (DT)—is managed primarily with benzodiazepines. Long-term AUD pharmacotherapy includes first-line options: naltrexone, an opioid antagonist that reduces cravings (avoided in hepatic dysfunction), and acamprosate, used post-withdrawal to maintain abstinence (avoided in severe renal dysfunction). Disulfiram, which causes highly unpleasant reactions when alcohol is consumed by inhibiting acetaldehyde metabolism, serves as a second-line deterrent. For Opioid Use Disorder (OUD), first-line medication-assisted treatment (MAT) is buprenorphine, a mixed agonist/antagonist, which is safer than methadone but requires the patient to be in early withdrawal upon induction to prevent acute withdrawal. Methadone, a full mu-agonist, is second-line and typically administered in controlled settings due to the risk of respiratory depression and diversion. Injectable naltrexone is a viable third-line option, provided the patient has 7 to 10 days of verified opioid abstinence before administration. Special populations, such as adolescents, older adults, and pregnant women, require tailored approaches and monitoring, including baseline and routine renal/hepatic function tests for all patients beginning pharmacotherapy.