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Annals of Pharmacy Practice and Pharmacotherapy

2026 Volume 6 Issue 1

Safe Deprescribing Requires More Than Medication Withdrawal: A Clinical Pharmacy Framework for Sequencing, Monitoring, Therapeutic Substitution, and Restart Decisions in Complex Polypharmacy


, ,
  1. Department of Deprescribing and Polypharmacy Management, Faculty of Pharmacy, University of Tokyo, Tokyo, Japan.
  2. Department of Clinical Pharmacy and Medication Safety, Faculty of Pharmacy, Kyoto University, Kyoto, Japan.
Abstract

Deprescribing is often described as the planned reduction or discontinuation of medicines whose harms, treatment burden, or limited expected benefit no longer justify continued use. That definition is necessary but incomplete for complex polypharmacy because a safe medication change does not end when a prescription is stopped. The clinical consequences of withdrawal depend on which medicine is changed first, what other medicines and conditions remain, whether symptoms represent withdrawal or recurrence, whether the original treatment need persists, and whether a stopped medicine should later be replaced or restarted. This Comment develops a proposed clinical-pharmacy framework that treats deprescribing as a reversible, monitored process rather than a one-way medication-removal task. It integrates four decision functions: sequencing medication changes under interacting risks; monitoring for withdrawal, recurrence, and effects of treatment substitution; reassessing whether an indication still requires therapy and, if so, whether a safer substitute is appropriate; and explicitly adjudicating restart decisions. The framework distinguishes medication-level change from patient-level benefit, appropriateness flags from individualized treatment plans, and restart from automatic evidence of deprescribing failure. Its purpose is to make the post-withdrawal treatment state clinically visible and to clarify where pharmacists can contribute regimen-level reasoning, follow-up design, communication, and continuity. The framework is conceptual, not prospectively validated. Drug class, frailty, cognition, care transitions, monitoring capacity, patient priorities, and health-system resources remain important boundaries. Evaluation should therefore test both clinical outcomes and whether the proposed decision states can be implemented, measured, and revised safely across settings.


How to cite this article
Vancouver
Tanaka K, Kobayashi Y, Nakamura T. Safe Deprescribing Requires More Than Medication Withdrawal: A Clinical Pharmacy Framework for Sequencing, Monitoring, Therapeutic Substitution, and Restart Decisions in Complex Polypharmacy. Ann Pharm Pract Pharmacother. 2026;6(1):31-40. https://doi.org/10.51847/1t2qIL7aTs
APA
Tanaka, K., Kobayashi, Y., & Nakamura, T. (2026). Safe Deprescribing Requires More Than Medication Withdrawal: A Clinical Pharmacy Framework for Sequencing, Monitoring, Therapeutic Substitution, and Restart Decisions in Complex Polypharmacy. Annals of Pharmacy Practice and Pharmacotherapy, 6(1), 31-40. https://doi.org/10.51847/1t2qIL7aTs
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