Section 06 · Monograph

Venlafaxine

Reviewed Nov 2026FDA label

Effexor XRSNRI

Black Box Warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders.
Anyone considering the use of venlafaxine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Pooled analyses showed increased suicidality risk with antidepressants versus placebo in patients under 18, and for those aged 18-24 there was an increase in risk for antidepressants versus placebo in short-term studies; this increase was not seen in patients over age 24, and there was a reduction in risk with antidepressants versus placebo in adults aged 65 and older.
Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide.
Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Venlafaxine is not approved for use in pediatric patients.

Major depressive disorder (MDD) in adultsFDA-labeled
Generalized anxiety disorder (GAD) — extended-release formulationFDA-labeled
Social anxiety disorder (social phobia) — extended-release formulationFDA-labeled
Panic disorder, with or without agoraphobia — extended-release formulationFDA-labeled

Migraine prophylaxis (off-label) — SNRI used for chronic and episodic migraine prevention, particularly when comorbid depression/anxiety is presentOff-label
Chronic tension-type headache prophylaxis (off-label)Off-label
Neuropathic pain / diabetic peripheral neuropathy (off-label)Off-label
Vasomotor menopausal symptoms (off-label)Off-label

Serotonin-norepinephrine reuptake inhibitor (SNRI): venlafaxine and its major active metabolite O-desmethylvenlafaxine inhibit neuronal reuptake of serotonin and norepinephrine
Weakly inhibits dopamine reuptake
Has no significant affinity for muscarinic, histaminergic, or alpha-1 adrenergic receptors in vitro, distinguishing it from tricyclic antidepressants
No monoamine oxidase inhibitory activity

Immediate-release, depression: initiate 75 mg/day in 2-3 divided doses with food; may increase in increments of up to 75 mg/day at intervals of no less than 4 days; max 375 mg/day
Extended-release, depression/GAD/social anxiety/panic disorder: initiate 37.5-75 mg once daily; may increase at intervals of no less than 4 days; typical target range 75-225 mg/day
Off-label migraine prophylaxis (not FDA-labeled dosing): clinical practice regimens commonly use the extended-release formulation in a similar general dose range (e.g., roughly 75-150 mg/day) — verify against current guideline sources, as this is not an FDA-approved indication or labeled regimen
Discontinuation: taper gradually over at least 2 weeks (longer with longer treatment duration) rather than abrupt discontinuation, due to discontinuation symptoms

Hepatic/renal impairment: dose reduction required (e.g., reduce total daily dose by 50% in moderate hepatic impairment; further reductions with renal impairment or hemodialysis) per label guidance

Hypersensitivity to venlafaxine, desvenlafaxine, or product components
Concurrent use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders, or use within 14 days of stopping such an MAOI (and starting an MAOI within 7 days of stopping venlafaxine) — risk of serotonin syndrome
Concurrent use with linezolid or intravenous methylene blue (both are MAOIs) — risk of serotonin syndrome

MAOIs: contraindicated — risk of serotonin syndrome; requires washout periods (14 days after stopping an MAOI before starting venlafaxine; 7 days after stopping venlafaxine before starting an MAOI)
Other serotonergic drugs (SSRIs, other SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, St. John's Wort): increased risk of serotonin syndrome
CYP2D6 inhibitors: increase venlafaxine levels and decrease active metabolite levels, but no dose adjustment is required because total active moiety exposure is largely unchanged
Anticoagulants, aspirin, NSAIDs, and other drugs affecting coagulation: increased risk of bleeding when combined with venlafaxine
CNS-active drugs/alcohol: caution regarding additive effects

Nausea
Somnolence
Dry mouth
Dizziness
Insomnia
Asthenia/fatigue
Sweating (diaphoresis)
Constipation
Sexual dysfunction (ejaculatory delay, decreased libido, erectile dysfunction in males; orgasm difficulty in females)
Sustained, dose-dependent increases in blood pressure
Hyponatremia (particularly in elderly patients)
Discontinuation symptoms with abrupt cessation (agitation, anxiety, dizziness, paresthesias/'electric shock' sensations, insomnia)

Blood pressure regularly throughout treatment, given risk of sustained hypertension
Serum sodium, particularly in elderly patients or those on diuretics (hyponatremia/SIADH risk)
Suicidality and clinical worsening, especially early in treatment and after dose changes
Signs of serotonin syndrome, especially when combined with other serotonergic agents
Weight and growth in pediatric/adolescent patients if used off-label
Lipid profile (dose-related increases in cholesterol reported)

Pregnancy: no adequate and well-controlled studies in pregnant women; animal studies showed decreased pup weight and increased stillbirths at maternally toxic doses
Third-trimester exposure has been associated with neonatal complications including respiratory distress, feeding difficulty, and seizures, requiring extended hospital observation in some cases
Lactation: venlafaxine and its active metabolite O-desmethylvenlafaxine are excreted into human breast milk; risk-benefit assessment needed before use in nursing mothers