The use of antidepressant medications in the United States has increased fivefold since the introduction of selective serotonin reuptake inhibitors (SSRIs) in the late 1980s.^1,2 Between 2015 and 2018, the percentage of U.S. adults who reported taking an antidepressant medication in the past 30 days was 13.2%, compared with 2.4% between 1988 and 1994.^1,2

Antidepressants are the most commonly prescribed medications for U.S. adults 20 to 59 years of age.³ Rates of depression and suicide have increased, primarily among those younger than 25 years.^4,5 The percentage of adults 18 to 25 years of age reporting a major depressive episode in the past year doubled from 8.8% in 2005 to 17% in 2020. During the same period, rates among adults 26 years and older increased only slightly from 6.2% to 7.1%.^6,7

The definition of a major depressive episode is based on the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria for major depressive disorder.^6,8 Five or more depressive symptoms must be present for at least two weeks, cause distress or functional impairment, and not be due to another medical or psychiatric condition. Symptoms include depressed mood, anhedonia, changes in weight or sleep patterns, fatigue, psychomotor agitation or retardation, feelings of worthlessness or guilt, impaired concentration, and recurrent thoughts of death.^6,8 Clinical trials of antidepressants often use major depressive episode as an inclusion criterion. Although most patients with clinician-identified depression do not meet diagnostic criteria for a major depressive episode, many are prescribed antidepressants.⁹

Second-generation antidepressants are the most common medications used to treat depression in the United States.¹⁰ These include SSRIs (e.g., escitalopram, paroxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g., duloxetine [Cymbalta], venlafaxine), serotonin modulators (e.g., nefazodone, trazodone), and atypical antidepressants (e.g., bupropion, mirtazapine).

Effectiveness

Despite thousands of clinical trials, the effectiveness of antidepressants is not well established. High-quality reviews of randomized controlled studies show a statistically significant improvement in depression with use of antidepressant medications.^11,12 A 2016 systematic review showed that the number needed to treat for response to treatment or remission is 9 for tricyclic antidepressants, 7 for SSRIs, and 6 for venlafaxine.¹¹ Outcomes of other studies challenge these conclusions, with minimal difference in symptoms between placebo and antidepressants, publication bias favoring effectiveness, and pharmaceutical industry sponsorship of most clinical trials.^11,13,14 A recent national survey of adults with depression revealed that those who used antidepressants had no improvement in health-related quality of life at two years of follow-up compared with those who did not use antidepressants.¹⁵

Psychotherapy (e.g., behavior therapy, cognitive therapy, cognitive behavior therapy, interpersonal psychotherapy, psychodynamic therapy, supportive therapy) is also a first-line treatment for depression.^16,17 The effectiveness of psychotherapy is similar to that of antidepressants in the primary care setting (relative risk [RR] = 1.03; 95% CI, 0.88 to 1.22).¹⁸ Evidence for cognitive behavior therapy is more robust than for other types of therapy.¹⁰ The combination of psychotherapy and pharmacotherapy may be more effective than either treatment alone for moderate or severe depression and may reduce risk of relapse and recurrence.^17,19,20