What is the recommended dosing for Effexor (venlafaxine) in adults with depression?

Venlafaxine (Effexor) Dosing for Depression in Adults

Start venlafaxine extended-release at 37.5-75 mg once daily, increase by 75 mg weekly as tolerated to reach the therapeutic target of 150-225 mg/day, with a maximum of 375 mg/day for severe or treatment-resistant depression. 1, 2

Initial Dosing Strategy

• Begin with 37.5 mg once or twice daily for the first week to minimize gastrointestinal side effects, particularly nausea 1
• The extended-release formulation allows once-daily dosing, improving adherence compared to immediate-release formulations 3
• Starting at 75 mg/day is acceptable in patients without significant medical comorbidities 4, 2

Titration Schedule

• Increase the dose by 75 mg every 4-7 days based on tolerability and clinical response 1
• The next step after 37.5-75 mg is 150 mg/day, which represents the lower end of the therapeutic range 1
• Most patients require 2-4 weeks to reach their target therapeutic dose 2

Therapeutic Target Range

• The optimal therapeutic dose is 150-225 mg/day for major depressive disorder, where dose-response relationships are most evident 4, 1, 2
• Doses of 75-225 mg/day were superior to placebo in outpatient studies, with clear dose-response relationships in this range 2
• Plasma concentrations of venlafaxine plus its active metabolite O-desmethylvenlafaxine should be 195-400 ng/mL for optimal therapeutic effect 4

Maximum Dosing for Severe Depression

• For treatment-resistant or severe depression (particularly inpatients), doses up to 375 mg/day are FDA-approved 2
• A mean dose of approximately 350 mg/day was effective in inpatient studies with melancholic depression 2
• Doses above 375 mg/day (up to 600 mg/day) have been used off-label in treatment-resistant cases, though this requires careful monitoring 5, 6
• No additional efficacy was demonstrated beyond 225 mg/day in most outpatient studies, though individual patients may benefit from higher doses 2

Critical Monitoring Requirements

• Monitor blood pressure at doses exceeding 150 mg/day, as venlafaxine can cause dose-dependent hypertension 4, 1
• Blood pressure increases are modest but occur in approximately 10% of patients at doses averaging 342 mg/day 6
• Check blood pressure before initiating therapy and regularly during dose escalation 1

Common Side Effects and Management

• Nausea is the most common side effect (dose-dependent) and the leading cause of discontinuation 1, 3
• Other frequent adverse effects include dry mouth, dizziness, somnolence, insomnia, sweating, and sexual dysfunction 4, 3
• Side effects are generally similar to SSRIs but with added noradrenergic effects at higher doses 3, 7
• At high doses (≥375 mg/day), patients report increased fatigue, concentration difficulties, sleepiness, and memory complaints more severely than at standard doses 6

Special Population Adjustments

Hepatic Impairment

• Reduce the total daily dose by 50% in patients with hepatic cirrhosis 2
• In Child-Pugh A or B hepatic impairment, venlafaxine clearance is reduced by more than half and elimination half-life doubles 2

Renal Impairment

• Reduce the total daily dose by 25-50% in patients with moderate to severe renal impairment (GFR 10-70 mL/min) 2
• In dialysis patients, reduce dose by 50% and administer after dialysis sessions 2

Elderly Patients

• Start at 50% of the standard adult dose (approximately 37.5 mg/day) in older adults 4
• Age alone does not significantly alter pharmacokinetics, but older adults are at higher risk for adverse drug reactions 4, 2

Discontinuation Protocol

• Never discontinue venlafaxine abruptly—always taper gradually over 10-14 days minimum 8, 1
• Venlafaxine has a well-documented discontinuation syndrome including dizziness, sensory disturbances, paresthesias, fatigue, myalgias, nausea, anxiety, and irritability 8, 1
• If withdrawal symptoms emerge, slow the taper further or temporarily increase the dose before resuming a slower taper 8

Duration of Treatment

• Continue treatment for 4-12 months after the first depressive episode to prevent relapse 4
• For recurrent depression (≥3 episodes), consider maintenance therapy for 1-2 years or longer 4
• Patients on continued venlafaxine experienced significantly lower relapse rates over 26-52 weeks compared to placebo in maintenance studies 2

Common Pitfalls to Avoid

• Do not increase doses too rapidly—weekly increments of 75 mg are appropriate, but faster titration increases nausea and dropout rates 1, 9
• Do not assume lack of efficacy before reaching 150 mg/day—subtherapeutic dosing is common in clinical practice 1, 2
• Do not overlook blood pressure monitoring at higher doses—hypertension can develop insidiously 1, 6
• Do not switch to another antidepressant without adequate dose optimization—many patients respond to dose increases who did not respond at lower doses 9, 3