Pharmacologic treatment of acute major depression and dysthymia. American College of Physicians-American Society of Internal Medicine.

M depression and dysthymia are two of the most common and debilitating illnesses. The World Health Organization estimates that worldwide, major depression is the fourth leading cause of loss of disability-adjusted life-years. Major depression is a clinical syndrome lasting at least 2 weeks, during which the patient experiences either depressed mood or anhedonia plus at least five of the following symptoms: depressed mood most of the day, nearly every day; markedly diminished interest or pleasure in most activities most of the day; significant weight loss or gain or appetite disturbance; insomnia or hypersomnia; psychomotor agitation or retardation; inappropriate guilt; diminished ability to think or concentrate, or indecisiveness; or recurring thoughts of death, including suicidal ideation. Dysthymia, by contrast, is a chronic but mild depressive disorder found in approximately 3% of community populations. It also causes significant impairment and is characterized by depressed mood, less severe than that in major depression, that is present on more days than not for 2 years. During this period, two of the following symptoms must also be present: appetite disturbance, insomnia or hypersomnia, decreased energy or fatigue, low selfesteem, decreased concentration or difficulty making decisions, or feelings of hopelessness. This guideline is based on an evidence report on pharmacotherapies for depression from the San Antonio Evidence-based Practice Center that was commissioned by the Agency for Healthcare Research and Quality (1). It answers the following questions: What is the evidence supporting the benefits of pharmacologic treatment? What are the data on the efficacy and side effect profiles of “newer” compared with “older” pharmacotherapies? How can the evidence assist physicians and patients in making informed decisions about treatment options? The lifetime risk for major depressive disorder ranges from 10% to 25% for women and 5% to 12% for men, with a point prevalence rate of 5% to 9% for women and 2% to 3% for men. Persons of all ages, ethnicities, and socioeconomic status experience the burden of depression. The prevalence of depressive disorders varies; it is lowest in community samples, intermediate in outpatient populations, and highest in inpatient settings. Because of the increasing prevalence of depression worldwide, especially in elderly persons, primary care physicians can expect to encounter and screen more patients with this condition (2) [2.2]. Three types of therapies have proven efficacy for depressive disorders: pharmacotherapy, psychotherapy, and electroconvulsive therapy. Because pharmacotherapy is the main tool of the primary care physician, it forms the focus of this guideline. Clinicians are faced with a multitude of antidepressants to choose from. These include “older” agents, such as the firstand second-generation tricyclic antidepressants, heterocyclics, and monoamine oxidase inhibitors. During the past decade, several “newer” classes of antidepressants have become available. The most notable of these is selective serotonin reuptake inhibitors (SSRIs). Lesser-known new agents include serotonin and noradrenaline reuptake inhibitors; selective norepinephrine reuptake inhibitors; reversible inhibitors of monoamine oxidase; 5-hydroxy-tryptophan2 (5-HT2) receptor antag* This paper, written by Vincenza Snow, MD, Steven Lascher, DVM, MPH, and Christel Mottur-Pilson, PhD, was developed by the Clinical Efficacy Assessment Subcommittee: David C. Dale, MD, Chair; William E. Golden, MD; Robert D. McCartney, MD; Keith W. Michl, MD; Stephen G. Pauker, MD; Sean R. Tunis, MD; Kevin B. Weiss, MD; Preston L. Winters, MD; and John J. Whyte, MD. Approved by the Board of Regents on 17 July 1999.