Beyond Addiction: Burden of Polypharmacy and Risk in Frail Patients with Substance Use Disorder

Substance use disorder (SUD) is a chronic and clinically complex condition, frequently complicated by significant organic and psychiatric comorbidities. Most patients are polymedicated and require opioid substitution programs (OSPs). This complexity is further exacerbated by drug-drug interactions, therapeutic duplication, and fragmentation of the healthcare system. This retrospective observational study analyses the prevalence of polypharmacy and associated pharmacotherapeutic risks in a cohort of 1050 patients with SUD treated at Drug Care Units (DCUs) in Tenerife (Canary Islands, Spain). Prescriptions were dominated by methadone (62%), antidepressants, and antipsychotics, often in combination with benzodiazepines. Significant polypharmacy (>10 active prescriptions) was observed in 2.3% of patients, while 8.1% received 6-10 medications and 37.2% were using 2-5 medications. Women showed a higher pharmacological burden, with 3.5% experiencing significant polypharmacy (>10 different prescriptions) compared with 1.1% of men. Overall, 31% of patients received antidepressants, 31% were treated with antipsychotics-frequently with concurrent use of multiple agents-and 6.4% received opioids outside the OSP. Therapeutic duplication was observed in 15.6% of patients for psycholeptics, 14.2% for psychoanaleptics, and 3.2% for antiepileptics. Additionally, 25.2% of patients reported self-medication, predominantly with benzodiazepines. These findings underscore the need for integrated pharmaceutical care programs incorporating individualized therapeutic review and deprescribing strategies to enhance the safety and efficacy of SUD treatment.