Skip to main content
Resources › Psychotropics A-Z › Venlafaxine | Effexor | Effexor
Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

Venlafaxine | Effexor

Clinical Overview

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) indicated for major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder. It was the first SNRI developed and demonstrates dose-dependent dual reuptake inhibition, with serotonin effects predominating at lower doses and norepinephrine effects becoming more prominent at higher doses.

Primary Clinical Applications

Venlafaxine is indicated for major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder. It may be particularly effective for treatment-resistant depression and patients with depression accompanied by fatigue or pain symptoms. The extended-release formulation allows for once-daily dosing and improved tolerability.

Mechanism and Clinical Benefits

Venlafaxine inhibits serotonin reuptake at lower doses (75-150 mg) and adds significant norepinephrine reuptake inhibition at higher doses (>150 mg). This dose-dependent dual mechanism may provide benefits for both emotional and physical symptoms of depression, as well as anxiety disorders. It has minimal activity at other receptors, reducing side effects.

Clinical Considerations

Venlafaxine can cause dose-related increases in blood pressure and requires monitoring, particularly at higher doses. It has a relatively short half-life (5 hours) requiring twice-daily dosing for immediate-release formulations, but the extended-release version allows once-daily dosing. The medication can cause significant discontinuation syndrome and requires careful tapering.

Prescribing Information

Dosing & Administration

Major Depressive Disorder:

  • Immediate Release: 75 mg daily in 2-3 divided doses, may increase by 75 mg every 4 days (maximum 375 mg daily)
  • Extended Release: 75 mg once daily, may increase by 75 mg every 4 days (maximum 225 mg daily)

Generalized Anxiety Disorder (XR only):

  • Initial: 75 mg once daily
  • Range: 75-225 mg once daily
  • Maximum: 225 mg once daily

Social Anxiety Disorder (XR only):

  • Dose: 75 mg once daily
  • Range: 75-225 mg once daily

Panic Disorder (XR only):

  • Initial: 37.5 mg once daily for 7 days
  • Target: 75 mg once daily
  • Range: 75-225 mg once daily

Administration:

  • Take with food to reduce nausea
  • XR: Swallow whole, do not crush or chew
  • Same time each day

Indications

  • Major depressive disorder
  • Generalized anxiety disorder (XR formulation)
  • Social anxiety disorder (XR formulation)
  • Panic disorder (XR formulation)

Contraindications

  • Hypersensitivity to venlafaxine
  • Use with MAOIs (within 14 days)
  • Use with linezolid or IV methylene blue

Warnings & Precautions

  • Boxed Warning: Increased risk of suicidal thoughts and behavior in patients under 25 years
  • Hypertension: Dose-related increases in blood pressure
  • Serotonin syndrome: Risk with concurrent serotonergic drugs
  • Discontinuation syndrome: Severe withdrawal symptoms, taper gradually
  • Activation of mania: Monitor in patients with bipolar disorder
  • Angle-closure glaucoma: Pupillary dilation may trigger attack
  • Abnormal bleeding: Increased risk with anticoagulants

Drug Interactions

  • MAOIs: Contraindicated – minimum 7-day washout from venlafaxine
  • CYP2D6 inhibitors: Increase venlafaxine active metabolite levels
  • Serotonergic drugs: Increased risk of serotonin syndrome
  • NSAIDs, aspirin: Increased bleeding risk
  • CNS depressants: Enhanced sedation

Adverse Reactions

Common (≥10%):

  • Nausea, headache, somnolence, dry mouth
  • Dizziness, insomnia, nervousness, sweating

Dose-related:

  • Hypertension (especially >225 mg daily)
  • Sexual dysfunction

Serious:

  • Severe discontinuation syndrome, serotonin syndrome
  • Sustained hypertension

Special Populations

  • Hypertension: Monitor blood pressure regularly, especially at higher doses
  • Renal Impairment: Reduce dose by 25-50% for moderate-severe impairment
  • Hepatic Impairment: Reduce dose by 50% for moderate impairment
  • Pregnancy: Category C – use only if benefits outweigh risks
  • Discontinuation: Very gradual taper required due to severe withdrawal syndrome
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.