New Research Highlights Underreported Risks of Deprescribing

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Polypharmacy, the concurrent use of 5 or more medications, is prevalent among older adults. While necessary for managing multiple chronic conditions, polypharmacy carries significant risks, including adverse drug events (ADEs) such as falls, cognitive impairment, hospitalization, and even mortality.¹ As a response, deprescribing—the clinically supervised process of reducing or stopping medications when risks outweigh benefits—has emerged as a strategy to mitigate these risks. However, deprescribing itself is not without potential harms, particularly adverse drug withdrawal events (ADWEs), which can range from mild symptoms to serious physiological consequences.² Recent research evaluates how ADWEs are reported in randomized controlled trials (RCTs) of deprescribing interventions and explores the criteria used to assess and quantify these events.³

“Our systematic review underscores the need for robust ADWE detection criteria with a step that assesses for causality, to improve the reporting and safety of deprescribing trials,” researchers wrote. “By addressing the limitations in the current methods and adopting a more standardized reporting framework, future research can ensure consistent and reliable results, ultimately enhancing clinicians' confidence in trial results.”

Methods

A systematic review was conducted following PRISMA guidelines, with database searches in Ovid Medline, Embase, and CENTRAL up to July 2024. Eligible studies included RCTs evaluating deprescribing interventions in adults aged 65 and older. Studies were screened using Covidence, and risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Data extraction focused on study characteristics, ADWE reporting criteria, and incidence rates.

Results

Of the 7,795 studies retrieved, 139 met inclusion criteria, but only 12 (8.6%) explicitly reported ADWEs. Studies varied in setting, sample size, and deprescribing approach. The most common methods for identifying ADWEs included:

• Naranjo ADWE Probability Scale: A structured algorithm assessing causality, offering high reliability but requiring trained reviewers.
• Clinical monitoring for withdrawal symptoms: Focused on specific known withdrawal effects but lacked broad applicability.
• ICD-10 codes: Provided standardized diagnostic classification but had limitations in sensitivity and specificity.
• Patient/caregiver self-report: Captured patient perspective but was subjective and potentially unreliable.
• Clinical judgment: Flexible but prone to variability and bias.

Across the 12 studies, 3,037 ADWEs were reported among 12,223 participants, with incidence rates varying significantly. Deprescribing was associated with an overall increase of 1.02 ADWEs per 100 person-months compared to controls, but heterogeneity was high (94.2%).

Discussion

The review highlights the inconsistency and underreporting of ADWEs in deprescribing trials. Many studies relied on subjective measures or lacked standardized assessment tools, leading to potential misclassification of events. The absence of causality assessment in most studies further complicates comparisons. Higher ADWE prevalence was noted in studies deprescribing sedative-hypnotics, likely due to well-documented withdrawal syndromes.

Researchers suggested future research should standardize ADWE reporting criteria, incorporate validated assessment tools, and ensure rigorous monitoring to balance the benefits and risks of deprescribing. Improved detection and reporting will enhance clinician confidence and patient safety in deprescribing practices.

Conclusion

Despite its importance, the review found ADWE reporting remains inconsistent in deprescribing RCTs. Researchers stated standardized methodologies are necessary to ensure reliable detection and accurate risk-benefit assessment in deprescribing interventions. They noted future trials should prioritize comprehensive ADWE evaluation to inform clinical decision-making and optimize medication management for older adults.

Clinical Implications

The review stated clinicians should be aware of the potential for ADWEs when deprescribing, especially for medications with known withdrawal effects. They noted standardized ADWE assessment tools should be integrated into deprescribing protocols to improve patient safety. Future guidelines should emphasize the importance of structured ADWE monitoring in clinical practice.

References

1. Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA. 1997;277(4):307-311.
2. O'Donnell LK, Ibrahim K. Polypharmacy and deprescribing: challenging the old and embracing the new [published correction appears in BMC Geriatr. 2022 Oct 3;22(1):777. doi: 10.1186/s12877-022-03465-x.]. BMC Geriatr. 2022;22(1):734. Published 2022 Sep 7. doi:10.1186/s12877-022-03408-6
3. Lee JJ, Bortolussi-Courval É, Filosa E, et al. Criteria to report adverse drug withdrawal events in clinical trials: A systematic review. J Am Geriatr Soc. 2025. doi:10.1111/jgs.19457