Adverse effect	Risk	Associated medications	Time to onset	Evidence
Gastrointestinal bleeding	Odds ratio = 1.55 (95% CI, 1.35 to 1.78)	SSRIs, especially when used with nonsteroidal anti-inflammatory drugs or antiplatelet drugs; risk mitigated by acid-suppressing medications	Anytime during treatment	Meta-analysis²⁷
Hepatotoxicity	Incidence = 0.5% to 3%	Nefazodone, bupropion, duloxetine (Cymbalta), trazodone	Anytime during treatment	Literature review ²⁸
Hyponatremia (sodium < 130 mEq per L [130 mmol per L])	Incidence = 0.06% to 2.6%	SSRIs, SNRIs, mirtazapine, TCAs	Within the first month	Literature review ²⁹
Osteoporosis and fractures	Hazard ratio = 1.88 (95% CI, 1.48 to 2.39) for fragility fracture	SSRIs, SNRIs	Over 10 years	Prospective cohort³⁰
QT prolongation	Dose dependent	Citalopram, escitalopram, amitriptyline U.S. Food and Drug Administration warns against exceeding recommended dose of citalopram (≤ 60 years of age, 40 mg per day; > 60 years, 20 mg per day)	At initiation Typically dependent on coexisting risk factors	Cross-sectional retrospective studies^31,32
Sexual adverse effects	Weighted mean incidence = 40% (95% CI, 28.3 to 52.6) across observational studies	Trend toward increased risk with escitalopram and paroxetine; decreased risk with bupropion	Within the first week	Meta-analysis^33,34
Suicidality	Age-related risk < 18 years: odds ratio = 2.39 (95% CI, 1.31 to 4.3) ≥ 18 years: odds ratio = 0.81 (95% CI, 0.51 to 1.2)	Duloxetine, fluoxetine, paroxetine, sertraline, venlafaxine	Not defined	Systematic review, meta-analysis of clinical reports³⁵
Weight gain (> 5%)	Rate ratio 1.21 (95% CI, 1.20 to 1.23) for SSRIs 1.17 (95% CI, 1.13 to 1.21) for SNRIs 1.16 (95% CI, 1.14 to 1.18) for TCAs	SSRIs, SNRIs, TCAs Decreased risk with bupropion	Over 10 years (highest risk in first two years)	Population-based cohort study, systematic review^23,36