The increased incidence of multimorbidities and polypharmacy is a major concern, particularly in the growing aging population. While polypharmacy can be beneficial, in many cases it can be more harmful than no treatment, especially in individuals suffering from psychiatric disorders, who have elevated risks of multimorbidity and polypharmacy. Age-related chronic inflammation and immunopathologies might contribute to these increased risks in this population, but the optimal clinical management of drug-drug interactions and the neuro-immune mechanisms that are involved warrants further investigation. Given that neurotransmitter systems, which psychiatric medications predominantly act on, can influence the development of inflammation and the regulation of immune function, it is important to better understand these interactions to develop more successful strategies to manage these comorbidities and complicated polypharmacy. I propose that expanding upon research in translationally relevant human
in vitro
models, in tandem with other preclinical models, is critical to defining the neurotransmitter-mediated mechanisms by which psychiatric drugs alter immune function. This will define more precisely the interactions of psychiatric drugs and other immunomodulatory drugs, used in combination, enabling identification of novel targets to be translated into more efficacious diagnostic, preventive, and therapeutic interventions. This interdisciplinary approach will aid in better precision polypharmacy for combating adverse events associated with multimorbidity and polypharmacy in the future.