Rational drug use in the treatment of depression.

New drugs are being developed for the management of depression in response to the growing awareness of the prevalence and disability associated with the disorder and the need for agents with improved side effect profiles. All antidepressants are equally effective for treating uncomplicated unipolar depression without psychotic features. For patients with atypical depression with prominent anxiety, agitation, sleep loss, and irritability, monoamine oxidase inhibitors are the first choice. Data are accumulating supporting the efficacy of selective serotonin reuptake inhibitors (SSRIs) in these depressive subtypes. Factors to consider when choosing an antidepressant include spectrum of adverse effects, long-term tolerability, dosing schedule, clinically significant drug interactions, underlying medical conditions, earlier response to therapy, and pharmacoeconomics. Based on these criteria, it is suggested that a trial with the SSRIs be attempted first. Venlafaxine and nefazodone are newer agents with mechanisms of action that have advantages over tricyclic antidepressants and monoamine oxidase inhibitors. Choosing a drug that is effective, tolerable, and convenient will improve the likelihood of achieving and maintaining a full remission. It will also decrease the morbidity and mortality of this very treatable disease.