case. The use of multiple drugs, even in fairly straightforward illnesses, is not an indicator of poor treatment and is not necessarily overmedication. Moreover, it is well accepted in pharmacology that it is impossible to accurately predict the side effects or clinical effects of a combination of drugs without studying that particular combination of drugs in test subjects. Knowledge of the pharmacologic profiles of the individual drugs in question does not assure accurate prediction of the side effects of combinations of those drugs; and effects also vary among individuals because of genome-specific pharmacokinetics. Therefore, deciding whether and how to reduce a list of medications (deprescribe) is often not simple and requires the experience and judgment of a practicing physician, as the physician must weigh the pros and cons of keeping the patient on the medication. However, such thoughtful and wise review is an ideal that too often does not happen, owing to problems such as poorly handled care transitions (poor continuity of care, usually because of siloed information), overworked physicians, and interventionism. Appropriate medical uses While polypharmacy is typically regarded as undesirable, prescription of multiple medications can be appropriate and therapeutically beneficial in some circumstances. “Appropriate polypharmacy” is described as prescribing for complex or multiple conditions in such a way that necessary medicines are used based on the best available evidence at the time to preserve safety and well-being. Polypharmacy is clinically indicated in some chronic conditions, including diabetes mellitus, but should be discontinued when evidence of benefit from the prescribed drugs no longer outweighs potential for harm (described below in Contraindications). Often certain medications can interact with others in a positive way specifically intended when prescribed together, to achieve a greater effect than any of the single agents alone. This is particularly prominent in the field of anesthesia and pain management – where atypical agents such as antiepileptics, antidepressants, muscle relaxants, NMDA antagonists, and other medications are combined with more typical analgesics such as opioids, prostaglandin inhibitors, NSAIDS and others. This practice of pain management drug synergy is known as an analgesia sparing effect. Examples A legitimate treatment regimen in the first year after a myocardial infarction may include: a statin, an ACE inhibitor, a beta-blocker, aspirin, paracetamol and an antidepressant. In anesthesia (particularly IV anesthesia and general anesthesia) multiple agents are almost always required – including hypnotics or analgesic inducing/maintenance agents such as midazolam or propofol, usually an