Antipsychotic polypharmacy remains a common practice despite evidence little evidence of efficacy compared to monotherapies and a well-documented increase in side effects for patients. A recent systematic review and meta-analysis published by Højlund and colleagues in The Lancet Psychiatry analyzed the prevalence of antipsychotic polypharmacy. The study spans 53 years and includes 517 studies and suggests that antipsychotic polypharmacy remains prevalent across all mental disorders. Indeed, on average, 24.8% of patients are prescribed antipsychotic polypharmacy. Schizophrenia spectrum disorders had the highest rates at 33.2% whereas bipolar disorder, intellectual disability, and dementia had lower prevalence rates ranging from 5.2% to 11.0%.

Evidence from the study made it clear that antipsychotic polypharmacy increases poor outcomes for patients, matching published literature. Poorer outcomes include increased risks of relapse (RR 1.42), psychiatric hospitalization (RR 1.24), and all-cause mortality (RR 1.19). Patients also experience more side effects, such as extrapyramidal symptoms (RR 1.63), dystonia (RR 5.91), and the need for anticholinergic medications (RR 1.91). Antipsychotic polypharmacy was also linked to worse global functioning, greater side-effect burden, and prolonged QT intervals, raising concerns about its tolerability and long-term impact on patient wellbeing. Perhaps most importantly, fewer than 10% of polypharmacy regimens involved evidence-based combinations.

Importantly, despite updated clinical guidelines discouraging polypharmacy, the prevalence of antipsychotic polypharmacy has actually increased in the last five decades, particularly in adults (27.4%) and inpatients (31.4%). There is disparity in its prevalence across the globe; varying from 15.4% in North America to 38.6% in Africa. Overall, this study’s findings highlight the urgent need for clearer guidelines surrounding polypharmacy and efforts to better align clinical practice with published guidelines. Reducing unnecessary antipsychotic polypharmacy and ensuring its use for treatment-resistant cases with evidence-based combinations is critical for positive patient outcomes and successful treatment strategies.

Reference:

Højlund M et al The Lancet Psychiatry 2024;11(12):975-989. Abstract