Table 2.
First-Line Antidepressant Medications for Major Depressive Disorder.*
| Drug Class and Agent | Dose | Adverse Effects | Clinical Considerations | Indications |
|---|---|---|---|---|
| SSRIs† | ||||
| Fluoxetine | 20–80 mg/day | Gastrointestinal and sexual side effects, agitation | Long-acting active metabolites decrease risk of discontinuation syndrome‡; 1-wk washout required when switching to another SSRI or SNRI; increased risk of drug interactions | Major depressive disorder; also FDA-approved for PMDD, OCD, bulimia, panic disorder |
| Sertraline | 50–200 mg/day | Gastrointestinal and sexual side effects, headache; generally acceptable side-effect profile | Risk of sexual side effects higher than with other SSRIs and SNRIs | Major depressive disorder; also FDA-approved for PMDD, OCD, panic disorder, PTSD, social anxiety |
| Paroxetine | 10–60 mg/day | Anticholinergic effects (weight gain, sedation, constipation), gastrointestinal and sexual side effects | Risk of discontinuation syndrome‡: may require slower taper; controlled-release formulation may decrease risk of discontinuation syndrome; increased risk of drug interactions; consider for patients with coexisting depression and anxiety | Major depressive disorder; also FDA-approved for PMDD, OCD, panic disorder, social anxiety, generalized anxiety disorder, PTSD |
| Fluvoxamine | 50–300 mg/day | Anticholinergic effects (weight gain, sedation, constipation), gastrointestinal and sexual side effects, anorexia, insomnia; poor side-effect profile | May have fewer associated sexual side effects than other SSRIs and SNRIs; consider for patients with coexisting depression and anxiety; increased risk of drug interactions | FDA-approved only for OCD; off-label use for major depressive disorder |
| Citalopram | 10–40 mg/day | Gastrointestinal and sexual side effects, sedation; acceptable side-effect profile | Black-box warning regarding doses >40 mg because of QT prolongation | Major depressive disorder; off-label use for anxiety disorders |
| Escitalopram | 5–20 mg/day | Gastrointestinal and sexual side effects | May be associated with a lower risk of headache, dizziness, sedation, and gastrointestinal side effects than other SSRIs and SNRIs; S-enantiomer of citalopram | Major depressive disorder; also FDA-approved for generalized anxiety disorder |
| SNRIs | ||||
| Venlafaxine | 37.5–225 mg/day (extended-reiease formulation) or twice daily (immediate-release formulation, sustained-release formulation) | Agitation, insomnia, tremor, hypertension, tachycardia, sweating, gastrointestinal and sexual side effects, headache, discontinuation syndrome‡: | Risk of discontinuation syndromê: may require slower taper; extended-release formulation may decrease risk of discontinuation syndrome; may increase energy; may help with anergia or attentional symptoms; risk of death from over-dose greater than with other first-line agents | Major depressive disorder; also FDA-approved for generalized anxiety disorder, social anxiety, panic disorder, neuropathic pain |
| Desvenlafaxine | 50–100 mg/day | Agitation, insomnia, tremor, hypertension, tachycardia, sweating, discontinuation syndrome‡: | Primary active metabolite of venlafaxine; risk of discontinuation syndrome‡; extended-release formulation may reduce risk of discontinuation syndrome; may increase energy; may help with anergia or attentional symptoms; may need to adjust dose in patients with renal insufficiency | Major depressive disorder; off-label use for anxiety disorders |
| Duloxetine | 60 mg total/day, administered once or twice daily | Agitation, insomnia, tremor, hypertension, tachycardia, sweating | May increase energy; may help with anergia or attentional symptoms; consider for patients with coexisting pain conditions | Major depressive disorder; also FDA-approved for generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, chronic musculoskeletal pain |
| Other agents | ||||
| Levomilnacipran | 20–120 mg/day | Agitation, sweating, hypertension, tachycardia, palpitations, dysuria | L-enantiomer of milnacipran; may increase energy; may help with anergia or attentional symptoms; fewer gastrointestinal side effects, weight gain, sedation, and sexual dysfunction than SSRIs and SNRIs | Major depressive disorder |
| Bupropion | 50–450 mg/day (extended-rei ease formulation) or twice daily (immediate-release formulation, sustained-release formulation) | Tachycardia, agitation, insomnia, seizures | Consider in combination with SSRI or SNRI; sustained-release and extended-release formulations allow for less frequent dosing and may increase adherence than immediate-re-lease formulation‡; may help with anergia or attentional symptoms; 0.4% increased risk of seizure at approved doses; contraindications include seizure disorder, bulimia or anorexia, alcohol or benzodiazepine withdrawal; not associated with sexual dysfunction | Major depressive disorder; also FDA-approved as aid to smoking cessation; extended-reiease formulation indicated for prophylaxis of seasonal depression; may be helpful for ADHD, attention problems, or anergia symptoms |
| Mirtazapine | 15–45 mg/day | Sedation, increased appetite, weight gain | Consider in combination with SSRI or SN Rl; consider for patients with coexisting depression and anxiety; lower dose may be more sedating; consider bedtime administration if insomnia or low appetite are present; should not be used if weight gain is an issue; associated with less sexual dysfunction than SSRIs or SNRIs and may aid in SSRI-induced sexual dysfunction | Major depressive disorder; off-label use for anxiety disorders |
| Vilazodone | 10–40 mg/day | Gastrointestinal side effects, insomnia | Associated with less sexual dysfunction than SSRIs and SNRIs; should be taken with food | Major depressive disorder |
| Vortioxetine | 10–20 mg/day | Gastrointestinal and sexual side effects, dry mouth | Effective in patients with cognitive dysfunction from major depressive disorder | Major depressive disorder, cognitive impairment (may improve processing speed) |
| Agomelatine | 25–50 mg/day | Headache, gastrointestinal side effects, fatigue, back pain, anxiety, abnormal dreams, weight gain | May help to normalize sleep cycle (melatonin agonist); increased risk (1–3%) of transaminitis; liver function should be checked at baseline, at adjustment of dose (at 3, 6, 12, and 24 wk), and thereafter when clinically indicated | Major depressive disorder; not available in United States |
*
ADHD denotes attention deficit-hyper activity disorder, FDA Food and Drug Administration, OCD obsessive-compulsive disorder, PMDD premenstrual dysphoric disorder, PTSD post-traumatic stress disorder, SNRI serotonin-norepinephrine-reuptake inhibitor, and SSRI selective serotonin reuptake inhibitor.
†
SSRIs may increase the risk of bleeding and should be used with caution in combination with nonsteroidal antiinflammatory drugs, aspirin, or other anticoagulants, or in patients who are at risk for bleeding.
‡
The discontinuation syndrome may involve flulike symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal.