Characterizing the ideal antidepressant therapy to achieve remission.

A paradigm shift in the management of depression has transpired in recent years with the modification of treatment goals toward remission, an outcome that transcends response. Pharmacotherapy, psychotherapy, electroconvulsive therapy, and combination therapies are treatment modalities available to the clinician for facilitating remission in depressed patients. For patients with moderate-to-severe depression, pharmacotherapy, either alone or in combination with other therapeutic approaches, is the treatment of choice. Antidepressants have heterogeneous effects on neurotransmitter systems that are manifested in different levels of selectivity and potency, influencing the drugs' safety profile through their potential for inducing drug-drug interactions. In terms of the pharmacokinetic-pharmacodynamic characteristics of antidepressants, a positive dose-response relationship has been shown to enhance the achievement of full remission because it allows the clinician to maximize drug dosage to optimize efficacy. Evidence from several studies indicates that treatment strategies that involve combined serotonergic and noradrenergic mechanisms result in pharmacologic synergism that leads to an enhanced antidepressant effect. This article identifies key characteristics of antidepressants that have been associated with greater efficacy.