Whenever a new psychotropic medication is prescribed or a patient’s physical health condition changes while on chronic psychotropic treatment, the following factors should be considered. • Can the underlying medical illness cause or exacerbate the presenting psychiatric symptomatology (e.g., hypothyroidism causing fatigue and depression)? • Do medications used to treat the underlying medical illness have potential for aggravating the psychiatric illness (e.g., corticosteroids and depression, mania or psychosis)?• Can the underlying medical condition affect the availability, metabolism, or elimination of the psychotropic medication (e.g., reduction of drug absorption after bariatric surgery, changes in protein binding in pregnancy, reduction of drug elimination in end-stage liver disease)? • Does any underlying genetic variability affect drug metabolism (e.g., more whites than other races are poor metabolizers of CYP2D6 an enzyme that metabolizes many psychotropic medications; more people of Southeast Asian descent have a particular variation of the major histocompatibility complex gene (HLA-B), namely, HLA-B* 1502, that increases risk for Steven–Johnsons syndrome or toxic epidermal necrolysis when treated with carbamazepine)? • Does the psychotropic medication cause harm to the underlying or newly developed medical condition (e.g., atypical antipsychotics and diabetes; drugs with teratogenic potential and pregnancy)? • Do the medications used to treat the medical illness interact with the psychotropic medication causing (a) change in serum level of an agent with a narrow therapeutic index (e.g., lithium toxicity with lithium and diuretics), (b) a serious adverse reaction during combination therapy (e.g., serotonin syndrome with a serotonergic antidepressant and triptans), and (c) loss of effcacy of medication (e.g., decreased effcacy of both phenytoin and carbamazepine when used in combination).