Polypharmacy: Deprescribing Frameworks

Polypharmacy creates a multiplicative pharmacological burden through predictable mechanisms. Drug-drug interactions increase exponentially with medication count: a patient on 5 medications has a 50% probability of a clinically significant interaction, rising to nearly 100% at 8 or more medications. Pharmacokinetic interactions occur at multiple levels — CYP450 enzyme inhibition (e.g., fluoxetine inhibiting CYP2D6, causing toxic accumulation of metoprolol or codeine therapeutic failure), enzyme induction (e.g., carbamazepine inducing CYP3A4, reducing efficacy of warfarin and oral contraceptives), and protein binding displacement (highly bound drugs like warfarin and phenytoin compete for albumin sites, transiently increasing free drug levels). Pharmacodynamic interactions produce additive or synergistic toxicity: combining anticholinergic medications (oxybutynin + diphenhydramine + paroxetine) creates cumulative anticholinergic burden causing delirium, urinary retention, and cognitive decline. Prescribing cascades represent a particularly insidious pattern in which a drug side effect is misidentified as a new condition and treated with an additional medication (e.g., amlodipine → peripheral edema → furosemide → hypokalemia → potassium supplement → GI upset → PPI). Deprescribing frameworks such as the Deprescribing.org algorithms provide structured approaches: identify target medication, assess indication and time-to-benefit...