Article May 1, 1998

Antidepressant Drugs: Disturbing and Potentially Dangerous Adverse Effects

Edmund C. Settle, Jr., M.D.

J Clin Psychiatry 1998;59(suppl 16):25-30

Article Abstract

Adverse effects associated with antidepressant drug therapy rarely cause significant morbidity ormortality. Nevertheless, the successful management of patients with depression requires recognitionof potential adverse effects that have serious consequences, which include the discontinuation of otherwiseeffective therapy. The aim of this overview is to highlight the more common and potentiallydeleterious adverse effects of both older and newer classes of antidepressant drugs. Major adverse effectsattributed to the tricyclic antidepressant drugs (TCAs) include conduction defects and lethaloverdose. Most worrisome with the selective serotonin reuptake inhibitor drugs (SSRIs) is the serotoninsyndrome. Although rare, this syndrome can be insidious and lethal. Recent trends toward the useof medication combinations and augmentation therapies significantly enhance the risk of serotoninsyndrome. Cognitive impairment also may occur, especially with the TCAs. Apathy is occasionally aproblem with SSRI therapy. The syndrome of inappropriate antidiuretic hormone (SIADH) has beenreported with most antidepressant drugs but appears to be more common with serotonergic agents andin elderly patients. Although seizures are uncommon in patients receiving antidepressant therapy, therisk must be understood by both the patient and the clinician. Adverse effects related to sexual functionare common, especially with TCAs, SSRIs, and venlafaxine. Sexual dysfunction often leads tononcompliance and self-discontinuation of therapy. Sleep disturbances are common in patients withdepression, and recent data illustrate how crucial sleep regulation is to mood. Antidepressant drugsvary in their sleep effects. Although antidepressant drugs can cause a variety of adverse effects, thesedrugs save lives and their benefits far exceed their risks.