When selecting and managing psychoactive medications in older people, it is equally important to focus on avoidance of toxicity as it is to focus on efficacy. Higher psychoactive medication load is associated with increased rate and risk of all cause hospitalization. The medication classes used to treat depression and related comorbidities include antidepressants, antipsychotics, stimulants, mood stabilizers, lithium, anxiolytics and sedative hypnotics. This discussion will examine considerations to help avoid medication related problems relevant to medications used to treat depression in the antidepressant pharmacological class.