Mechanism-Informed Pharmacotherapy Optimization and Deprescribing: A Redox-Mitochondrial Framework

Area of Science:

• Gerontology and Pharmacology
• Mitochondrial Biology and Redox Homeostasis
• Clinical Pharmacology and Medication Management

Background:

• Current pharmacotherapy for multimorbidity often overlooks cumulative treatment burden and individual physiological reserve.
• Mitochondrial dysfunction and redox imbalance are key factors in disease vulnerability and drug toxicity but are underutilized in medication reviews.
• Existing medication review and deprescribing strategies may not adequately address the complex interplay of factors in patients with multiple chronic conditions.

Purpose of the Study:

• To integrate mechanistic, translational, and clinical literature on redox-mitochondrial biology and its implications for pharmacotherapy in multimorbidity.
• To propose a novel framework, redox-mitochondrial reasoning, to guide medication review and deprescribing.
• To enhance the assessment of treatment intolerance, functional decline, and cumulative medication burden by considering a patient's adaptive capacity.

Main Methods:

• A narrative review integrating literature on redox-mitochondrial biology, drug liabilities, polypharmacy, frailty, and deprescribing.
• Searches conducted through 2024 with targeted updates through June 2026.
• Development of structured tables and a prioritization algorithm to translate concepts into practical medication review signals.

Main Results:

• Identified shared biological processes (mitochondrial dysfunction, redox imbalance) influencing disease vulnerability and drug toxicity.
• Illustrated pharmacological plausibility of drug-class-specific mitochondrial liabilities with clinical and preclinical examples.
• Proposed a conceptual framework and heuristic aids (vulnerability strata, algorithm) for medication review.

Conclusions:

• Redox-mitochondrial reasoning offers a complementary approach to traditional medication review and deprescribing.
• This framework can help interpret treatment intolerance and functional decline as potential mismatches between drug exposure and patient adaptive capacity.
• The proposed conceptual tools should be used alongside established deprescribing methods, benefit-harm assessments, and shared decision-making.