Anti-Depression Meds: Drug Classes, Trial Results, Side Effects

Anti-depression meds, or antidepressants, are prescription drugs used to treat depression; prescribers also use them for anxiety, pain and insomnia^[2]. The most commonly prescribed groups are SSRIs, SNRIs and NDRIs such as bupropion, chosen because they treat a broad range of depressive and anxiety disorders with fewer side effects than older drugs^[2].

In 2023, 11.4% of U.S. adults said they took prescription medication for depression, according to the National Health Interview Survey^[1]. Use was more than twice as common among women (15.3%) as among men (7.4%)^[1].

Those figures count people taking medication, not people with the condition. For how common depression itself is, see the depression statistics and major depressive disorder pages; for trends in who takes these drugs, see antidepressant use statistics.

Medication is one of two first-line options. The 2022 VA/DoD guideline gives a strong recommendation that uncomplicated major depression be treated with either psychotherapy or medication alone, based on patient preference^[7]. The trial evidence for talk therapy is covered in cognitive behavioral therapy for depression.

SSRIs (selective serotonin reuptake inhibitors) include sertraline, escitalopram and fluoxetine. The FDA lists nausea, tremor, nervousness, sleep problems, sexual problems, sweating, agitation and tiredness as their common side effects^[3].

SNRIs act on both serotonin and norepinephrine. Their common side effects overlap with SSRIs and add dry mouth, constipation and dizziness; the FDA lists a rise in blood pressure as a less common but serious effect^[3].

Atypical antidepressants do not fit the other groups. The FDA lists weight gain and drowsiness among mirtazapine's common side effects, and seizures among bupropion's less common but serious ones^[3].

Tricyclics and MAOIs are older classes and carry more side effects, though NIMH notes they may be the best option for some people^[2]. MAOIs require avoiding foods such as aged cheese, wine and others containing tyramine, and the FDA warns against combining SSRIs, SNRIs, tricyclics, trazodone or mirtazapine with them^[3].

What guidelines list as first choices

For a first medication, the VA/DoD guideline suggests any of bupropion, mirtazapine, an SNRI, an SSRI, trazodone, vilazodone or vortioxetine, without ranking them^[7]. It suggests against starting with esketamine, ketamine, MAOIs, nefazodone or tricyclics^[7].

Medications for postpartum depression

Two drugs target postpartum depression specifically. Brexanolone is given as a continuous IV infusion over 60 hours in a certified facility^[3]. Zuranolone, approved in August 2023, was the first oral drug for the condition and is taken once daily for 14 days^[12].

Therapy and drug options after birth are compared in postpartum depression treatment.

A 2018 network meta-analysis in The Lancet compared anti-depression meds across 522 double-blind trials and 116,477 adults with major depression^[4]. Every one of the 21 antidepressants it studied was more effective than placebo, with odds ratios for response ranging from 2.13 for amitriptyline to 1.37 for reboxetine^[4].

The authors rated the certainty of that evidence as moderate to very low, and they judged 9% of trials to be at high risk of bias^[4]. When all trials were counted, odds ratios between active drugs ranged only from 1.15 to 1.55 for efficacy^[4].

Average benefit is modest. An FDA analysis of patient-level data from 232 placebo-controlled trials (73,388 participants, 1979 to 2016) found drugs beat placebo by 1.75 points on the 17-item Hamilton depression scale^[5].

That average hides a split. In the same analysis, 24.5% of people on a drug had a large response versus 9.6% on placebo, and the authors estimated that about 15% of participants get a substantial benefit beyond the placebo effect^[5]. The gap between drug and placebo widened as baseline depression got more severe^[5].

In short, these drugs help on average, and some people respond far more than others, with no reliable way yet to predict who^[5]. The VA/DoD guideline found insufficient evidence to recommend for or against pharmacogenetic testing to choose a drug^[7].

NIMH says antidepressants usually take 4 to 8 weeks to work, and that problems with sleep, appetite, energy and concentration often improve before mood lifts^[2].

The NIMH-funded STAR*D trial put numbers on that. Participants took an average of six weeks to reach a response and nearly seven weeks to reach remission on their first drug, citalopram^[6]. NIMH noted that full benefits may not appear until 10 or 12 weeks^[6].

Treatment usually continues after symptoms ease. The VA/DoD guideline gives a strong recommendation to keep taking an antidepressant at the therapeutic dose for at least six months after remission to lower the risk of relapse^[7].

STAR*D enrolled 4,041 outpatients at 41 sites and was, when published, the largest and longest study of depression treatment^[6]. About a third of participants reached remission on the first drug, and about half were symptom-free after two treatment steps^[6].

Across all four steps, almost 70% of those who stayed in the study reached remission^[6]. Dropout grew at each step, from 21% after the first to 42% after the third, and people who needed more steps were more likely to relapse^[6].

The VA/DoD guideline lists four next steps after a partial or no response, without ranking them: switching to another antidepressant, switching to psychotherapy, adding psychotherapy, or adding a second-generation antipsychotic^[7]. After two or more failed drug trials, it suggests repetitive transcranial magnetic stimulation; for severe cases with features such as psychosis or severe suicidality, it recommends electroconvulsive therapy^[7].

Esketamine for treatment-resistant depression

Esketamine (Spravato) is a nasal spray given under supervision in a certified health care setting^[11]. Its label, revised in January 2025, covers treatment-resistant depression in adults, either alone or with an oral antidepressant^[11].

The label carries a boxed warning for sedation, dissociation, respiratory depression and misuse, and requires monitoring for at least two hours after each dose^[11]. NIMH notes it often acts within a couple of hours^[2].

NIMH lists upset stomach, headache and sexual dysfunction as common side effects of SSRIs and other antidepressants, and says they are generally mild and tend to fade with time^[2]. The FDA's class charts add drug-specific effects, such as weight gain with mirtazapine and dry mouth, constipation and blurred vision with tricyclics^[3].

Combining antidepressants with other serotonin-acting products, such as triptans for migraine or the supplement St. John's wort, can cause serotonin syndrome, a rare but life-threatening reaction^[2].

Antidepressants as a class carry a boxed warning about suicidal thoughts and behavior in young people^[8]. The warning rests on pooled data from 24 short-term trials of 9 antidepressants in more than 4,400 children and adolescents, in which suicidal thinking or behavior occurred in 4% of those on a drug versus 2% on placebo; no suicides occurred in those trials^[8].

NIMH describes the current scope: children, teenagers and young adults under 25 may have more suicidal thoughts or behavior on antidepressants, especially in the first few weeks or after a dose change, and people of all ages should be watched closely early in treatment^[2]. As of 2019, the FDA listed fluoxetine as the only antidepressant approved for children with depression, and fluoxetine and escitalopram as the only ones approved for teens^[3].

A 2024 meta-analysis of 79 studies and 21,002 patients found that 31% of people who stopped an antidepressant reported at least one discontinuation symptom, compared with 17% of people who stopped a placebo^[9]. After subtracting that placebo effect, the authors put the true incidence at about 15%, or one in six to seven people^[9].

Severe symptoms were uncommon, at 2.8% after stopping an antidepressant versus 0.6% after stopping placebo^[9]. Desvenlafaxine, venlafaxine, imipramine and escitalopram were linked with more frequent symptoms^[9].

A 2025 JAMA Psychiatry review of 50 randomized trials with 17,828 participants found people stopping an antidepressant had about one more symptom in the first week than those who continued or stopped placebo^[10]. Dizziness was the most common, with 5.52 times the odds seen after stopping placebo, and stopping was not associated with depressive symptoms in the trials that measured them^[10].

NIMH and the FDA both advise against stopping a prescribed antidepressant without a health care provider, who can lower the dose gradually^[2][3].