Is a dose reduction of venlafaxine from 150mg every other day to 75mg daily acceptable?

From the Guidelines

Reducing venlafaxine from 150mg every other day to 75mg daily is not recommended without medical supervision, as it may lead to discontinuation symptoms or a relapse of depression. When considering a dose reduction, it is essential to consult a doctor, who may recommend a more gradual tapering schedule, such as reducing by 37.5mg increments every 1-2 weeks, to minimize the risk of side effects 1. Venlafaxine has a relatively short half-life, and taking it every other day can lead to fluctuating blood levels and potentially unstable mood, whereas daily dosing is typically preferred for more consistent effects. Some key points to consider when adjusting venlafaxine dosage include:

• The recommended therapeutic range for venlafaxine plus O-desmethylvenlafaxine is 195-400 ng/mL, according to the AGNP-TDM expert group consensus guidelines 1
• The level of recommendation for routine monitoring of venlafaxine is 2, indicating that suggested therapeutic ranges are plasma concentrations at therapeutically effective doses obtained from fixed dose studies 1
• Any changes to antidepressant medication, including venlafaxine, should be done under the guidance of a healthcare provider to avoid discontinuation symptoms or a relapse of depression. The goal is to maintain therapeutic levels of the medication while minimizing side effects, and a doctor can help determine the most appropriate dosing regimen based on individual needs and response to the medication.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Initial Treatment The recommended starting dose for venlafaxine tablets, USP is 75 mg/day, administered in two or three divided doses, taken with food. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible.

The dose reduction from 150mg every other day to 75mg daily is acceptable as it is within the recommended dosing range and the reduction is gradual. Dose reduction should be done with caution and patients should be monitored for any symptoms. The recommended starting dose is 75 mg/day, which is the target dose in this reduction. 2

From the Research

Dose Reduction of Venlafaxine

• The question of whether a dose reduction of venlafaxine from 150mg every other day to 75mg daily is acceptable can be informed by several studies 3, 4, 5, 6, 7.
• A study on venlafaxine withdrawal syndrome 3 highlights the importance of gradual dose reduction to avoid withdrawal symptoms, but does not directly address the specific dose reduction in question.
• Another study 4 mentions a patient who was maintained on 150mg/day of venlafaxine after experiencing QTc interval prolongation at a higher dose, and also notes that the patient had previously responded well to 75mg/day, suggesting that 75mg/day may be an effective dose for some patients.
• A study on the tolerability of high-dose venlafaxine 5 found that doses up to 600mg/day were tolerated, but does not provide direct guidance on the safety of reducing the dose from 150mg every other day to 75mg daily.
• A pharmacokinetic study 6 found that dividing a daily 150mg dose of venlafaxine into 2 or 3 doses provided equivalent total exposure and peak plasma concentrations of venlafaxine and its active metabolite, suggesting that the dosing regimen may be flexible.
• A review of venlafaxine extended-release 7 notes that therapeutic responses were evident at doses of 75-225mg/day, and that 75mg/day was an effective dose in some studies, providing some support for the idea that 75mg/day may be a suitable dose for some patients.

Key Considerations

• The safety and efficacy of reducing the dose of venlafaxine from 150mg every other day to 75mg daily may depend on individual patient factors, such as the patient's medical history, response to treatment, and tolerance of the medication 3, 4, 5.
• Gradual dose reduction is generally recommended to avoid withdrawal symptoms 3.
• The pharmacokinetic properties of venlafaxine suggest that the dosing regimen may be flexible, but the clinical implications of this flexibility are not fully understood 6.