PAD Refills

What is the role of venlafaxine (Effexor XR, generics) in the management of menopause-associated hot flashes?

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Conclusion: Venlafaxine is recommended in menopause guidelines as an off-label option for hot flashes but only when menopause hormone therapy (MHT) is contraindicated or not suitable. The largest clinical trial initiated treatment with 37.5 mg per day then increased the dose to 75 mg after one week. The body of evidence supporting venlafaxine is limited, thereby introducing uncertainty into estimates of its effectiveness and tolerability.

The BC Provincial Academic Detailing (PAD) Medications for menopause-associated vasomotor and genitourinary symptoms delivers evidence and practical drug information for the most commonly prescribed estrogen and progestogen products (oral, transdermal, vaginal).¹ Visit www.bcpad.ca to book a session with an academic detailing pharmacist in your area. We received this question during PAD sessions: What is the role of venlafaxine in the management of hot flashes?

Guidelines^2-5

Menopause guidelines list venlafaxine as a non-hormonal, off-label option for vasomotor symptoms (hot flashes) but only when MHT is contraindicated or not suitable. In 2021, the Society of Obstetricians and Gynecologists identified venlafaxine as a first-line option for the management of hot flashes in breast cancer survivors. However, these recommendations preceded the recent availability of neurokinin receptor antagonists (fezolinetant, elinzanetant) which are non-hormonal and approved by Health Canada for the treatment of moderate to severe hot flashes. 

Evidence^6-9

The body of evidence for venlafaxine for the management of hot flashes is not extensive. The largest trial (339 participants without a history of hormone-dependent cancer) used venlafaxine at a starting dose of 37.5 mg for 1 week, then increased to 75 mg per day. From a baseline of approximately 8 hot flashes per day, venlafaxine reduced the frequency of hot flashes to approximately 4 per day at the end of the 8-week trial (placebo reduced hot flash frequency by approximate 2 per day). The effect was similar in a smaller trial enrolling 191 breast cancer survivors. These trials do not follow the regulatory criteria for a drug approval clinical trial, so it is challenging to put the results into context of other medications approved for hot flashes (MHT, neurokinin receptor antagonists). There are a few other trials enrolling breast cancer survivors, but they are too small (less than 100 participants) to quantify venlafaxine’s effectiveness relative to other options with certainty.   

Some practical considerations:^6-13

• Despite the more limited evidence for venlafaxine, at a drug cost of < $10 per month it may be more affordable than the newer neurokinin receptor antagonists for some people (fezolinetant ~ $180 per month)
• From the largest trial it appears that a reduction in hot flashes occurs during weeks 1-2 with maximal effect occurring during weeks 4-6
• Adverse events captured during the short-term trials include dry mouth, decreased appetite, nausea, constipation, somnolence, asthenia, dizziness, insomnia
• Venlafaxine does not interact with tamoxifen, whereas some other antidepressants do (e.g., fluoxetine, paroxetine)
• Venlafaxine has the potential to cause withdrawal symptoms upon discontinuation and it warrants an individualized tapering plan
• Additional monitoring may be warranted for patients on concomitant chemotherapies or supportive therapies that increase blood pressure, heart rate or increase the risk of hyponatremia or bleeding. Blood pressure monitoring is recommended in the National Comprehensive Cancer Network Survivorship guideline for those prescribed venlafaxine

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¹BC PAD Service Medications for Menopause-Associated Vasomotor and Genitourinary Symptoms (May 2025); ²Yuksel J Obstet Gynaecol Can 2021 (PMID:34390867); ³NAMS Position Statement Menopause 2023 (PMID:37252752); ⁴BMS Consensus Statement 2025; ⁵AMS Non-Hormonal Treatments for Menopausal Symptoms; ⁶Joffee JAMA Intern Med 2014 (PMID:24861828); ⁷Loprinzi Lancet 2000 (PMID:11145492); ⁸Bordeleau J Clin Oncol 2010 (PMID:21060031); ⁹Boekhout J Clin Oncol 2011 (PMID:21911720); ¹⁰McKesson Canada (accessed December 30, 2025) drug cost only; ¹¹BC PAD Service Antidepressants Newsletter 2020; ¹²Liamis AJKD 2008 (PMID:18468754); ¹³National Comprehensive Cancer Network Guidelines Survivorship Version 2.2025