Medication appropriateness is an important component of medicines management, but multimorbidity creates therapeutic decisions in which a medication can be indication-concordant yet still be poorly aligned with the patient’s overall clinical situation. Disease-specific benefit, treatment burden, practical workability, and patient priorities may diverge, change over time, or operate at different levels of care. To develop an evidence-bounded conceptual model of therapeutic optimization that treats these dimensions as analytically distinct and requires their explicit reconciliation rather than assuming that appropriateness, medication count, or deprescribing alone defines success. This original non-empirical article integrates recent and foundational evidence on multimorbidity, polypharmacy, medication review, adverse medication outcomes, treatment burden, shared decision-making, patient priorities, and medicines-review feasibility. The synthesis is conceptual rather than a systematic review and does not estimate intervention effects. The analysis distinguishes medication-level appropriateness from patient-level therapeutic value. It proposes that optimization requires four concurrent questions: whether clinically meaningful benefit remains plausible within the relevant time horizon; what workload and adverse consequences treatment imposes; whether the regimen is practically executable given patient and system capability; and whether its purpose is concordant with what matters to the patient. Discordance among these dimensions should trigger explicit trade-off deliberation and reversible, monitored decisions rather than automatic continuation or discontinuation. Therapeutic optimization in multimorbidity is proposed as a dynamic reconciliation process, not a one-time appropriateness judgment. The model requires prospective validation, context-sensitive measurement, and testing across heterogeneous patients, regimens, clinicians, and health systems.
