The Art of Subtraction: A Structured Clinical Approach to Deprescribing in Complex Medication Regimens

Medical training has long emphasized the prescribing decision—when to initiate a medication, at what dose, and for how long. The equally consequential question of when and how to stop a medication has historically received far less attention. That imbalance is beginning to shift. As polypharmacy reaches near-epidemic proportions among older Americans—data from the CDC suggest that nearly 40% of adults aged 65 and older take five or more prescription medications—the clinical and ethical imperative to deprescribe has never been more pressing.

Deprescribing, broadly defined as the intentional reduction or discontinuation of medications when the risks of continued use outweigh the benefits in the context of an individual patient's goals and clinical status, is not simply the inverse of prescribing. It demands a distinct skill set: the ability to assess cumulative medication burden, anticipate discontinuation syndromes, navigate patient expectations, and manage the institutional inertia that often keeps inappropriate medications in place long after their clinical rationale has expired.

Understanding the Scope of the Problem

Before a clinician can deprescribe effectively, it helps to understand the mechanisms by which inappropriate medications accumulate. Prescribing cascade—the phenomenon in which a new drug is added to treat an adverse effect of an existing one, which is misinterpreted as a new clinical condition—is among the most common culprits. A patient started on a calcium channel blocker develops ankle edema; a diuretic is added; the diuretic causes urinary urgency; an anticholinergic agent is prescribed in response. Each step is individually defensible; the cumulative burden is not.

Additionally, medications initiated for acute conditions are frequently continued indefinitely. Proton pump inhibitors prescribed for hospital stress ulcer prophylaxis remain on discharge summaries for years. Benzodiazepines prescribed for situational anxiety become long-term fixtures. Statins initiated for primary prevention in patients who have since developed terminal illness continue to generate monthly refills. These are not failures of intent—they are failures of systematic review.

Step One: Conduct a Structured Medication Review

The foundation of any deprescribing effort is a comprehensive, structured medication reconciliation that goes beyond simply listing what a patient is taking. Clinicians should verify the indication for each medication, confirm whether that indication remains active, assess whether the drug is achieving its therapeutic goal, and evaluate the current risk-benefit balance in light of the patient's evolving clinical picture.

Several validated tools can support this process. The Beers Criteria, published by the American Geriatrics Society, identifies medications that are potentially inappropriate in adults aged 65 and older based on evidence of harm, limited efficacy, or safer alternatives. The STOPP/START criteria offer a complementary European-derived framework that many US clinicians have found useful for structuring systematic review. For patients with multiple chronic conditions, the Medication Appropriateness Index (MAI) provides a ten-item checklist that evaluates each drug across dimensions including indication, effectiveness, dosage, and clinical interactions.

Clinicians should also apply the Good Palliative-Geriatric Practice (GP-GP) algorithm, which categorizes medications as either disease-modifying, preventive, or symptomatic—a distinction that becomes especially important when aligning the medication list with a patient's goals of care.

Step Two: Sequence and Prioritize Discontinuation

Not all medications can or should be stopped simultaneously. Prioritization should account for the magnitude of potential harm from continued use, the likelihood and severity of discontinuation effects, the patient's willingness to engage in the process, and the prescribing history of each drug.

As a general rule, medications with the highest risk of adverse effects and the weakest remaining indication should be addressed first. Anticholinergic agents—particularly those with high anticholinergic burden scores, such as diphenhydramine, oxybutynin, and certain tricyclic antidepressants—are frequent early targets in geriatric patients given their association with cognitive impairment, falls, and urinary retention.

Drugs with significant physiological dependence require a structured taper rather than abrupt cessation. Benzodiazepines should be reduced by no more than 25% every one to two weeks, with the rate slowed further if withdrawal symptoms emerge. SSRIs and SNRIs carry discontinuation syndrome risk—particularly with short half-life agents like paroxetine and venlafaxine—and should be tapered over weeks to months depending on duration of use. Corticosteroids used chronically require gradual reduction to allow adrenal recovery. Beta-blockers should never be abruptly discontinued in patients with ischemic heart disease due to rebound tachycardia and angina risk.

Step Three: Communicate the Decision Effectively

Patient communication is where many deprescribing efforts stall. Patients who have taken a medication for years may interpret a discontinuation recommendation as a signal that their condition has worsened, that their prescriber is giving up on their care, or that cost rather than clinical judgment is driving the decision. Proactively addressing these concerns is not merely courteous—it is clinically necessary.

Effective deprescribing conversations share several characteristics. They frame discontinuation as an active, positive clinical decision rather than a withdrawal of treatment. They acknowledge the patient's experience with the medication and validate any concerns about stopping. They set clear expectations about what symptoms to monitor, when to follow up, and under what circumstances the medication might be restarted.

A useful communication framework is the "PAUSE" approach: Present the rationale clearly; Acknowledge patient concerns; Understand individual preferences; Set a monitoring plan; Establish a re-evaluation timeline. Shared decision-making tools, including patient-facing handouts from the Deprescribing.org initiative (a Canadian resource widely used by US clinicians), can supplement verbal counseling and improve patient adherence to the discontinuation plan.

Step Four: Address Liability Concerns Directly

Fear of medicolegal consequences is a documented barrier to deprescribing. Clinicians worry that stopping a medication—particularly one with a guideline-supported indication—may expose them to liability if the patient experiences an adverse outcome that could be attributed, however loosely, to discontinuation.

This concern, while understandable, is not well-supported by the evidence on malpractice claims. Liability in deprescribing cases is more likely to arise from inadequate documentation and absent follow-up than from the decision to discontinue itself. Thorough documentation of the clinical rationale, the patient's informed consent or assent, the monitoring plan, and scheduled reassessment intervals creates a defensible record of thoughtful, individualized care.

It is also worth noting that the liability calculus cuts both ways. Continuing a medication that causes harm—a fall from a sedating agent, a gastrointestinal bleed from prolonged NSAID use, cognitive decline from high anticholinergic burden—carries its own liability exposure. Inaction is not a neutral choice.

Building a Culture of Medication Review

Sustainable deprescribing is not a one-time intervention—it is a practice culture. Health systems that have embedded structured medication reviews into annual wellness visits, transitions of care protocols, and pharmacist-led chronic disease management programs have demonstrated measurable reductions in potentially inappropriate prescribing and associated adverse events.

For individual clinicians, beginning with a single patient panel audit—identifying the five patients carrying the highest medication burdens and applying a structured review to each—can build both the skill and the confidence to make deprescribing a routine part of practice. The goal is not minimalism for its own sake. It is ensuring that every medication a patient takes is earning its place on the list.