New and Emerging Classes of Antidepressants

Kiran Rabheru, MD, CCFP, FRCP, ABPN, Physician Leader, Geriatric Psychiatry Program, Regional Mental Health Care and Chair, Division of Geriatric Psychiatry, Associate Professor of Psychiatry, University of Western Ontario, London, ON.

Depression is the most common psychiatric disease in the elderly. Over 30% of community-dwelling elderly suffer from subsyndromal depression and over 10% of hospitalized elderly have syndromal major depressive disorder (MDD). Depression is frequently a persistent and recurrent disorder leading to increased morbidity and mortality, as well as poor quality of life.

Early antidepressant medications, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) were discovered through astute clinical observations. These first-generation medications are effective because they enhance serotonergic and/or noradrenergic function. Unfortunately, the TCAs also block histaminic, cholinergic and alpha-1 adrenergic receptor sites, causing unwanted side effects such as weight gain, dry mouth, constipation, urinary retention, confusion, drowsiness and dizziness. MAOIs interact with tyramine to cause potentially lethal hypertension and cause dangerous interactions with a number of prescribed and over-the-counter medications.1

A major goal of antidepressant development is to improve on preceding drug classes for greater specificity, fewer unwanted side effects and more rapid onset of action.