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

Effexor (Venlafaxine) Dosing for Depression and Anxiety

For adults with depression or anxiety, start venlafaxine extended-release at 75 mg once daily, with a therapeutic target range of 150-225 mg/day for most patients, as clinical improvement is evident as early as 1-2 weeks at these doses. 1

Initial Dosing Strategy

• Begin with venlafaxine XR 75 mg once daily in the morning, as the extended-release formulation permits convenient once-daily dosing due to its sufficiently long elimination half-life 1
• The 75 mg starting dose has demonstrated efficacy in placebo-controlled trials and is generally well tolerated 2, 3
• Do not use 37.5 mg as an initial therapeutic dose—this lower dose is intended only for gradual tapering when discontinuing treatment 1

Dose Titration and Therapeutic Range

• Target 150-225 mg/day for most patients with depression or anxiety, as this range shows optimal efficacy with dose-dependent improvements in both psychic and somatic anxiety symptoms 1
• Clinical improvement becomes evident as early as 1-2 weeks, particularly at 150-200 mg/day doses 1, 4
• Allow 4-6 weeks at the target dose for an adequate therapeutic trial before considering further dose adjustments 1
• Dose-response data demonstrate statistically significant improvements in primary efficacy parameters at weeks 1-2 with 150-200 mg/day, with continued improvement through week 12 4

Higher Dose Considerations

• For severe or treatment-resistant depression, particularly in inpatients, doses may be increased up to a maximum of 375 mg/day 2, 5
• Studies in hospitalized patients with melancholia used venlafaxine doses titrated in the range of 150-375 mg/day (mean dose approximately 350 mg/day) with demonstrated efficacy 2
• Higher doses (225-375 mg/day) may exhibit better efficacy and shorter latency to response compared to standard doses, though they carry increased risk of adverse effects 5, 6

Special Population Adjustments

• Hepatic impairment: Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment (Child-Pugh A or B), as venlafaxine clearance decreases by approximately 50% and elimination half-life doubles in cirrhotic patients 2
• Renal impairment: Reduce dose by 25% in patients with mild to moderate renal impairment (GFR 10-70 mL/min), and by 50% in patients undergoing hemodialysis, as venlafaxine elimination half-life is prolonged by 50-180% 2, 1
• Elderly patients: Consider starting at lower doses (approximately 50% of standard adult starting dose) due to significantly greater risk of adverse drug reactions in older adults 7

Critical Monitoring Requirements

• Monitor blood pressure and pulse at baseline and during treatment, as venlafaxine is associated with sustained hypertension, increased blood pressure, and increased pulse, particularly at higher doses 1, 8
• Prescribe with caution in patients with cardiac disease, as cardiac conduction abnormalities have been reported 1
• Monitor height and weight at baseline and during treatment 1
• Watch for behavioral activation, agitation, hypomania, or mania, and monitor for suicidal thinking and behavior in patients through age 24 years, as venlafaxine may be associated with greater suicide risk than other SNRIs 1

Discontinuation Protocol

• Taper venlafaxine gradually over 10-14 days to minimize withdrawal symptoms, as a discontinuation syndrome has been reported following missed doses or acute discontinuation 1, 9
• Use the 37.5 mg dose for gradual tapering when stopping treatment 1

Therapeutic Drug Monitoring

• The recommended therapeutic plasma concentration range for venlafaxine plus O-desmethylvenlafaxine is 195-400 ng/mL, though this is classified as a level 2 recommendation (suggested therapeutic ranges from fixed-dose studies) rather than strongly recommended 10
• Therapeutic drug monitoring may be useful but is not routinely required for most patients 10

Common Adverse Effects

• The most frequently reported adverse events include nausea, dizziness, somnolence, insomnia, dry mouth, asthenia, sweating, and abnormal ejaculation 3, 4
• Dose-dependent dizziness and sedation can be minimized by starting low and titrating cautiously 1
• These adverse effects are generally consistent with the SSRI/SNRI class and are similar in incidence to fluoxetine and paroxetine 3