Want a hormone-free way to manage hot flashes? The evolving landscape of menopause management includes more than just hormone therapy. There is a new non-hormonal FDA-approved medication for hot flashes that changes the way women+ can beat the heat, and more of these types of medication could be on the way. There are also non-hormonal medications prescribed “off-label.” Knowledge is power! Learn about your non-hormonal options.
Non-hormonal medications for hot flashes
Hot flashes are one of the most common menopause symptoms, impacting 80% of women+.
You have choices on your menopause journey, especially around how you manage symptoms.
While you may be most familiar with hormonal options, they’re not the best choice for every woman+. It may be a personal decision or for medical reasons.
The effectiveness of these medications varies and comes with its own set of considerations, including the age at which you start taking HT and potential side effects.
There are also non-hormonal medications that can help you manage hot flashes, including FDA-approved medications and those used “off-label,” which means they are used to treat symptoms for which they were not originally intended when receiving FDA approval.
FDA-approved hot flash medication
For moderate-to-severe hot flashes, there are two non-hormonal medications approved by the Food and Drug Administration (FDA).
They are:
- Brisdelle™ (paroxetine)
- VEOZAH™ (fezolinetant)
Paroxetine was the first non-hormonal option and was approved by the FDA in 2014.
It took nearly 10 years before a new class of drugs came on the market targeting an area of the brain responsible for thermoregulation (regulation of body temperature).
Veozah™ was the first to emerge and received FDA approval in 2023. There is also a similar drug currently in late-stage development.
Let’s break down these medication options.
Paroxetine
Brisdelle™ (paroxetine) is a selective serotonin reuptake inhibitor (SSRI), a class of drugs used to treat mental health conditions like depression and anxiety. A low dose (7.5 mg) can be used to treat hot flashes.
At the time of approval, it was significant for women+ because they had no other non-hormonal medications for hot flashes.
The approval of the medication was not without controversy. The FDA advisory committee initially voted not to approve it due to a “Black Box” warning (the highest safety-related warning issued by the FDA) about the potential for paroxetine to increase suicidal thoughts. There was also a reluctance due to questions raised about its effectiveness.
But, without another hormone-free drug on the market for hot flashes, the low dose was approved, given its potential benefit.
Clinical results
For hot flash treatment, paroxetine works by reducing blood flow in blood vessels.
In studies, women+ saw results quickly, as early as 1 or 2 weeks for moderate symptoms. When used for depression (at a higher dose), it takes up to 6 weeks to experience an improvement.
The most common side effects were nausea, fatigue, and dizziness.
For almost a decade, this was the only FDA-approved non-hormonal option. That changed in 2023 when VEOZAH™ hit the market.
VEOZAH™ – a new type of treatment
VEOZAH™ (fezolinetant) is a breakthrough medication because it belongs to a new class of drugs that targets the part of the brain responsible for thermoregulation. It is not an antidepressant.
It works by blocking a specific receptor in the brain known as the neurokinin B receptor. This receptor plays a role in regulating the body’s temperature. A review of fezolinetant studies found the drug was as effective as estrogen hormone therapy at reducing hot flashes.
Reported side effects include:
- headaches
- dizziness
- nausea
- fatigue
- cold-like symptoms
Interestingly, some women+ experience more hot flashes when they first start the medication. Since fezolinetant (VEOZAH™) is a newer and specialized medication, it’s much more expensive than SSRIs, SNRIs, and gabapentin, which have generic versions available, some of which are used off-label for menopause symptoms.
As with all medications, some people should not take the drug. Talk to your doctor about other medications you’re taking to ensure they won’t impact how VEOZAH™ works or might not be safe to use in your particular situation.
Also, it’s not cheap! Foro example, the average monthly cost is $500+ on GoodRx, with most charging around $570 but some pharmacies more than $700. That price tag is generating headlines as much as the novel mechanism for which VEOZAH™ targets hot flashes.
A patient assistance program is available for those who qualify. (While there are no income requirements, if you have insurance through a state or federal program, you aren’t eligible. The maximum benefit is $1,300 a year.)
Elinzanetant is still in development
VEOZAH™ may not be the only option for long.
Another drug, in late-stage development, targets the brain but in a slightly different way.
Elinzanetant is the first dual antagonist, targeting both NK-3 and NK-1 receptors. VEOZAH™ targets just NK-3. These are estrogen-sensitive neurons in the brain that regulate body temperature.
A phase III study of women+ in 9 countries found Elinzanetant significantly reduced vasomotor symptoms (hot flashes and night sweats) in post-menopausal women.
The medication also shows promising results for sleep disturbances. Again, it’s still in development.
Keep reading…
VEOZAH: Medical Breakthrough Gives Women+ More Hot Flash Treatment Options
VEOZAH (fezolinetant) is a new breakthrough medication for hot flashes, that’s non-hormonal. It can reduce the frequency and severity.
Other hormone-free medication options
While there are only two FDA-approved, hormone-free hot flash medications, several drugs are used off-label.
These include:
- Other SSRIs and SNRISs
- Anti-seizure medication
- Blood pressure medication
Let’s explore each one.
Other SSRIs and SNRIs
Even though only one antidepressant medication was approved for the use of hot flashes, it’s not a woman’s only option. There are other SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) that are used off-label to alleviate mild to moderate, natural or surgically-induced menopausal hot flashes.
These drugs were originally developed for depression and anxiety. They are not as effective for hot flashes as estrogen hormonal therapy but may still be a helpful option for some women+, especially for those who already suffer from either condition or can’t/have chosen not to use hormone therapy.
Common SSRI or SNRI medications include
- paroxetine (Brisdelle™) – FDA approved
- citalopram (Celexa®)
- escitalopram (Lexapro®)
- fluoxetine (Prozac®)
- duloxetine (Cymbalta®)
- venlafaxine (Effexor®)
- sertraline (Zoloft®)
- desvenlafaxine (Pristiq®)
They usually have a two-week onset of action. Some women experience nausea or dizziness at first, but this usually resolves after one or two weeks.
Symptom improvement can vary significantly from person to person. While one SSRI/SNRI may work very well for some people, providing the desired relief from symptoms with minimal side effects, the same medication might not be as effective for others or could cause significant side effects.
Three side effects — reduced sexual desire and response and weight gain — are often especially concerning for women+, since these issues are commonly experienced during the menopause journey.
There can be differences in the type and/or frequency of side effects. For example, paroxetine has a lower incidence of causing insomnia, while fluoxetine and sertraline tend to have a reduced risk of weight gain.
Gabapentin for hot flashes
Gabapentin (Neurontin®) is a medication that’s used for controlling seizures and to help with nerve pain from diabetes or shingles.
Gabapentin can reduce the number and intensity of hot flashes.
Dizziness or tiredness is common during the first week of taking it, but usually gets better in two weeks and goes away in four weeks.
Higher doses of gabapentin seem to be just as good as estrogen therapy for cooling down severe hot flashes. However, at this higher dose, side effects like dizziness, headaches, and feeling confused are more common, which makes it less appealing for many women+.
Since it can cause drowsiness and doesn’t stay in the body for very long, taking it at bedtime might be a good option for women+ who are having trouble sleeping because of hot flashes. It’s important to know that medications for seizures, including gabapentin, have a warning about the rare chance of developing suicidal thoughts or behaviors.
Gabapentin is recommended by The Menopause Society in its 2023 non-hormonal position statement.
Lyrica
Pregabalin (Lyrica) is another anti-seizure medication that’s used off-label to treat hot flashes and is structurally related to gabapentin. This medication is typically taken 2 times a day versus 3 times a day with gabapentin.
In a study of 163 women, of which 40% had a history of cancer, vasomotor symptoms decreased by 59% with the lower dose of 75 mg twice a day and 61% for those taking 150 mg twice a day.
The studies showed taking this medication may cause drowsiness and impact cognitive abilities.
Because it’s a controlled substance that can be abused, and may cause weight gain, unlike gabapentin, pregabalin was not recommended by The Menopause Society in their 2023 position statement.
Clonidine for hot flashes
Clonidine is a blood pressure medication that has been shown to have a modest impact on hot flashes.
However, The Menopause Society says it’s used infrequently because of adverse side effects, including:
- hypotension (low blood pressure)
- lightheadedness
- headache
- dry mouth
- dizziness
- sedation
- constipation
Also, if you suddenly stop taking it, your blood pressure can rise significantly.
The Menopause Society believes there are more effective treatment options with fewer side effects, so it does not recommend it.
While it showed improvement compared to placebo, they found clonidine was also less effective than SSRIs, SNRIs, and gabapentin.
Choosing the Right Medication
Hot flashes are among the most common menopausal symptoms, and they can cause both physical and mental distress.
Thankfully, besides hormone therapy and integrative modalities like acupuncture, there are many non-hormonal medication options that can bring relief.
We’ve detailed 36 non-hormonal techniques, mind-body therapies, non-hormonal medications, herbal remedies, and lifestyle modifications in our pausitive health non-hormonal 101 guide.
Your experience with hot flashes may vary from your friends and colleagues. Every woman’s journey is unique, making the choice of the right non-hormonal medication a personal one.
It’s important to weigh factors such as:
- individual health concerns
- the intensity and frequency of hot flashes
- underlying medical conditions
- other drugs you may be taking with which there may be interactions
- medication costs
- possible side effects
By addressing hot flashes, you may also reduce some of the accompanying negative effects (e.g. sleep issues) and risks (e.g. hot flashes during sleep as a potential indicator of women+ at a greater risk of developing Alzheimer’s) associated with hot flashes.
Yet, a medication’s impact on other aspects of menopause remains uncertain, such as mood swings associated with hot flashes, the well-being of the bladder and vagina, heart, sexual health, bone health, as well as maintaining a healthy weight.
You may explore other non-hormonal medications that can help with various symptoms of the menopause journey, including those used to treat vulvar and vaginal atrophy (VVA) and urinary conditions.
Connect with your healthcare practitioner to discuss your options and determine the best one for your situation.
And, don’t suffer in silence!
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Lisa Miller, PharmD, BCPS, MSCP
This content was made possible through a collaboration with Dr. Lisa Miller. She is a clinical pharmacist and a North American Menopause-Certified Practitioner with a graduate degree in clinical mental health counseling.
Dr. Miller is the owner of Women's Precision Health, LLC and works with women on mindset, hormones, and their medications, developing individualized plans for a balanced body and mind. Dr. Miller is also the Assistant Dean of the Orlando Campus of the University of Florida College of Pharmacy and a Clinical Professor. In addition to working with midlife women, she also has research interests in women's health and women's mental health.
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Home | VEOZAH®
Veozah | GoodRX
At $550 A Month, New Menopause Hot Flash Drug May Be Out of Reach For Many Women | Forbes
Welcome to the VEOZAH Savings Program | VEOAH®
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Hot Flashes Yet Another Early Indicator for Alzheimer’s Disease | The Menopause Society™
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