What is Effexor (venlafaxine) used for and how is it typically prescribed?

Effexor (Venlafaxine): Clinical Uses and Prescribing

Effexor (venlafaxine) is FDA-approved for major depressive disorder and is also a first-line medication for neuropathic pain and anxiety disorders, prescribed as a serotonin-norepinephrine reuptake inhibitor (SNRI) with typical dosing starting at 37.5-75 mg daily and titrating to 150-225 mg daily. 1, 2

Primary Indications

Major Depressive Disorder

• FDA-approved indication for treating major depressive disorder in adults 1
• Efficacy established in 6-week controlled trials for outpatients and 4-week trials for inpatients with melancholic depression 1
• Demonstrated effectiveness in maintaining antidepressant response for up to 52 weeks in patients with recurrent depression 1
• May show superiority over fluoxetine in treating melancholia and anxiety symptoms associated with depression 2

Neuropathic Pain

• First-line medication for painful diabetic peripheral neuropathy (DPN) and painful polyneuropathies of mixed origins 2
• Does NOT show efficacy in postherpetic neuralgia (PHN) 2
• Frequently used as a coanalgesic combined with opioids for neuropathic cancer pain 2

Anxiety Disorders

• Effective for generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder, panic disorder, and obsessive-compulsive disorder 3
• May be superior to fluoxetine for treating anxiety symptoms in depressed patients 2
• Duloxetine is the only SNRI with FDA approval for pediatric anxiety, but venlafaxine is used off-label 2

Prescribing Algorithm

Starting Dosage

• Begin with 37.5 mg once or twice daily 2
• For depression: 75 mg/day in divided doses is the typical starting therapeutic dose 4
• Extended-release formulation allows once-daily dosing; immediate-release requires 2-3 times daily 2

Titration Schedule

• Increase by 75 mg each week as tolerated 2
• Requires 2-4 weeks to reach efficacious dosage of 150-225 mg/day 2
• Maximum dose: 225 mg/day for neuropathic pain; up to 375 mg/day for severe or resistant depression 2, 4

Duration of Adequate Trial

• 4-6 weeks at target dose before determining treatment failure 2
• Some patients show response as early as Week 1, particularly at higher doses 5

Critical Safety Considerations

Cardiovascular Monitoring

• Monitor blood pressure regularly - dose-dependent increases occur in 3-13% of patients depending on dose 2, 1
• Prescribe with caution in patients with cardiac disease due to reported cardiac conduction abnormalities 2
• Control hypertension before initiating treatment 1
• Check pulse and blood pressure at each visit 2

Discontinuation Protocol

• Must taper slowly when discontinuing - withdrawal syndrome is well-documented 2
• Abrupt cessation causes anxiety, irritability, electric shock-like sensations, dizziness, nausea, and confusion 1
• Do not stop within 7 days of starting an MAOI 1

Black Box Warning

• Increased suicidal thinking and behavior in patients up to age 24 years 1
• Monitor closely for new or worsening depression, anxiety, agitation, panic attacks, or unusual behavioral changes 1

Other Serious Adverse Effects

• Serotonin syndrome (life-threatening when combined with MAOIs, triptans, or other serotonergic drugs) 1
• Mydriasis (avoid in uncontrolled narrow-angle glaucoma) 1
• Abnormal bleeding risk, especially with concurrent NSAIDs or warfarin 1
• Hyponatremia, particularly in elderly patients 1

Common Adverse Effects

Most frequent side effects include nausea (6% discontinuation rate), somnolence, insomnia, dizziness, constipation, sweating, and sexual dysfunction 5, 6

• Nausea typically resolves within 1-3 weeks of therapy 5
• Overall discontinuation rate comparable to newer antidepressants and superior to tricyclic antidepressants 5

Contraindications

• Allergy to venlafaxine 1
• Uncontrolled narrow-angle glaucoma 1
• Concurrent MAOI use or within 14 days of MAOI discontinuation 1

Drug Interactions

• Absolute contraindication with MAOIs due to serotonin syndrome risk 2, 1
• Venlafaxine has minimal effect on CYP450 system compared to other antidepressants 2
• Cimetidine may increase venlafaxine levels 1

Clinical Advantages

• Dual mechanism (serotonin and norepinephrine reuptake inhibition) may provide superior efficacy in severe depression compared to SSRIs 5, 6
• Faster onset of action than traditional antidepressants, with some responses by Day 4-7 5
• Fewer anticholinergic effects and less cardiotoxicity than tricyclic antidepressants 6
• Much safer in overdose than tricyclic antidepressants 7