Venlafaxine is part of a family of drugs called serotonin norepinephrine reuptake inhibitors (SNRIs) most commonly used to treat anxiety and depression. In lower doses, they are effective in decreasing the frequency and severity of hot flashes. For more information on venlafaxine see the Prescriber’s Digital Reference (PDR).

Take one tablet at the same time daily, with or without food. Many providers recommend patients take venlafaxine at night because it can cause drowsiness, but the rule of thumb is to take it at a time when you’ll remember. Make it part of your daily routine. For example: Take it before you brush your teeth every night.

Please log in to your Ro account and message your provider. Your provider should be your first point of contact regarding questions about medication efficacy, side effects, and whether or not you would benefit from a change in dose or even a change in medication.

Paroxetine should not be used if any of the following apply: – History of suicidal thoughts or attempts unless paroxetine is used under the direction of a psychiatrist – History of self-injurious behavior unless paroxetine is used under the direction of a psychiatrist – History of bipolar disorder unless paroxetine is used under the direction of a psychiatrist – History of manic or depressive episodes unless venlafaxine is used under the direction of a psychiatrist – Patients with uncontrolled high blood pressure – History of serotonin syndrome – Patients taking medication for depression, bipolar disorder, or anxiety-including a TCA, SSRI, or SNRI (see the full list of potential drug interactions here in the drug interactions section) – People taking MAOIs or who have taken MAOIs in the previous 2 weeks – People with a history of long QT syndrome or who are taking drugs that lengthen the QT interval – People with moderate-to-severe liver disease – People with moderate-to-severe kidney disease – People who are pregnant, trying to become pregnant, or nursing. – Children under the age of 18 – People with bleeding disorders, or who are taking medications that increase their risks of bleeding, should discuss this with their provider before taking venlafaxine. In most cases, an alternative treatment strategy will be used.

For a full list of contraindications and precautions, see the PDR. Please note that Rory patients under the age of 40 are not eligible for treatment with paroxetine.

Venlafaxine is well tolerated by most patients, but all medications can have side effects. These include:

– Decreased sex drive or difficulty with orgasm – Headache – Hypertension – Nausea – Constipation – Diarrhea – Blurred sision – Insomnia – Drowsiness – Xerostomia (dry mouth) – Hyperhidrosis (excessive sweating) – Abdominal pain – Tremors

For a full list of side effects, see the PDR.

Contact your provider and all of your healthcare providers if you experience any new symptoms after beginning venlafaxine for hot flashes.

If you have any serious signs or symptoms like (but not limited to) palpitations, lightheadedness, confusion, muscle rigidity, or very elevated body temperature, please seek out emergency medical treatment. If your symptoms do not improve after three months, make an appointment to see your healthcare provider in person to discuss other possible causes of your hot flashes.

Hot Flashes/Flushes Overview

Hot flashes/flushes are short episodes of intense heat sensation of the head, neck, and chest. When it occurs with a red face, neck, and/or chest it is called a hot flush. Some women experience sweating and/or palpitations (a sense of the heart beating irregularly) during these episodes. They can occur at any time without warning and usually last 3–5 minutes. However, they can vary from 30 seconds to 30 minutes. Some women have hot flashes/flushes up to 20 times per day or more. Hot flashes/flushes can disturb sleep and can be awkward when they occur inexplicably in social situations.

The most common symptom of menopause and perimenopause is hot flashes/flushes, which are estimated to occur in up to 80% of women. Bothersome hot flashes can occur day or night. Nighttime hot flashes often cause night sweats and can interrupt a woman’s sleep.

Your plan: Venlafaxine

Your provider has reviewed your medical information and has prescribed venlafaxine to treat your hot flashes/flushes. Venlafaxine is part of a family of drugs called serotonin norepinephrine reuptake inhibitors (SNRIs). These drugs are most commonly used to treat anxiety and depression, but some of them have been studied and have been found to be effective at decreasing the frequency and intensity of hot flashes/flushes. When used to treat hot flashes, the dosages are typically lower than those used for treating depression, resulting in a lower incidence of side effects.

Venlafaxine is recommended by the North American Menopause Society (NAMS) for the treatment of hot flashes/flushes in doses ranging from 37.5–150 mg. Typical doses for depression are 150–225 mg per day. It is common for medications to be used at different dosages for different conditions based on providers’ clinical experience with the medication and studies of uses that were not included in the original FDA approval. For more information on venlafaxine, see the Prescribers’ Digital Reference (PDR).

Read carefully all of the material provided, along with the package insert and the information in the Prescribers’ Digital Reference (PDR).

Remember, the plan your provider has provided is just one plan for the treatment of hot flashes. Reach out to your provider if you would like to explore the different plans for the treatment of hot flashes offered by Rory, or if you have any questions or concerns after reading the information provided here.

Menopause is defined as a woman not having her period for 12 months. The ovaries stop producing large amounts of estrogen and progesterone and women no longer ovulate. Hormonal changes and symptoms usually begin before this happens, during a time called “perimenopause.” During the perimenopausal period, large fluctuations in hormone levels are thought to cause symptoms including irregular menstrual cycles, headaches, mood changes, insomnia, weight gain, breast pain (mastodynia), and hot flashes/flushes. With the onset of menopause, a dramatic decrease in estradiol (the body’s primary estrogen) and progesterone causes a host of changes in the body, including:

– Hot flashes: This is the most common symptom of menopause affecting over 75% of women during midlife. These symptoms typically last for 5–7 years but can last for up to 10–15 years in some women. If you have any of these symptoms, you may benefit from reading about the options available from your provider. – Absence of menstrual cycles: This is the hallmark of menopause. Once women stop ovulating, their uterine lining no longer grows and sluffs off as it does during a normal cycle. – Loss of bone density: Estrogen blocks the development of cells that cause the breakdown of bone called “osteoclasts.” When these cells are allowed to go unchecked by estrogen, bone density is lost. When bone density drops below a certain point, the result is a disease called osteoporosis. People with osteoporosis have a higher risk of bone fractures, including hip fractures, wrist fractures, and vertebral fractures. – Weight gain and bloating: Estrogen plays an important role in regulation of fat tissue and many women find that maintaining their weight becomes very difficult during this time. – Mood changes: Mood changes, like depression, are common during perimenopause and menopause. – Sleep disturbances: Sleep disturbance may be due to night sweats, but some women also have sleep problems separate from their night sweats. If you have menopause associated sleep disturbances, you may benefit from reading about the options available from your provider. – Increased risk of cardiovascular disease – Vaginal changes: These include vaginal shrinkage, loss of vaginal folds (rugae), loss of vaginal lubrication, vaginal itching and discomfort, and painful sex (dyspareunia). – Urinary symptoms: These can mimic a urinary tract infection (UTI), including urinary frequency, urgency, and painful urination. UTIs are more frequent, as well.

Although perimenopause and menopause are challenging times in a woman’s life, certain conditions that are worsened by higher estrogen levels actually improve after menopause. These include symptoms due to premenstrual syndrome (PMS), endometriosis, uterine fibroids, adenomyosis, and symptoms related to heavy, painful periods.

Are there specific health concerns that I should know that become more important during, and after, the menopausal transition?

Menopause does not mean that your general health will automatically deteriorate. However, preventive healthcare needs do change around this time. This is partly due to menopause itself and partly due to age. Here are some of the most important things to consider as you enter the perimenopausal/menopausal years:

Breast cancer screening: Breast cancer is the second most common cancer in women and the second most common cause of cancer-related deaths. The lifetime risk of breast cancer is about 12% or one in eight women—and most of these cancers occur in women with no specific risk factors. The risk for breast cancer increases with age with most women being diagnosed after the age of 50. Women aged 40–49 have a higher risk than younger women but not as high as after the age of 50.

Cancers diagnosed earlier have a better prognosis with a higher chance of survival. Many medical organizations have made recommendations about breast cancer screening. In general, screening for breast cancer with mammography in average-risk women should begin sometime between the ages of 40 and 50, depending on which recommendations are followed. Screening should be done every one or two years and continue to age 74.

Osteoporosis screening: One of the important functions of estrogen is to maintain bone density by inhibiting the development of cells that break down bone, called osteoclasts. The steep decline in estrogen levels that accompany menopause causes a decrease in bone density.

Osteoporosis is diagnosed when bone density decreases beyond a certain point. Osteopenia is a milder form of loss of bone density. These conditions greatly increase the risk of bone fractures. Fractures cause significant suffering and can even lead to death in the case of hip fractures.

Screening can help diagnose osteoporosis or osteopenia before a fracture, and treatment can be initiated to decrease the risk of fractures. The United States Preventive Services Task Force (USPSTF) recommends screening for osteoporosis in women aged 65 and older without risk factors for osteoporosis and for postmenopausal women younger than 65 who are at increased risk of osteoporosis. Screening is done with a dual-energy x-ray absorptiometry (DEXA) scan. The most commonly used tool to screen for fracture risk is the FRAX calculator. Some risk factors include smoking, caucasian race, rheumatoid arthritis, heavy alcohol use (three or more drinks per day), and people taking glucocorticoids (e.g. prednisone and hydrocortisone) for any condition.

Cervical cancer screening: Cervical cancer screening continues to be important throughout and after the transition to menopause. The USPSTF recommends cervical cancer screening with pap testing every three years or pap testing plus testing for high-risk HPV testing every five years. Women should stop cervical cancer screening if they fulfill one of the following: – Women who have had a hysterectomy (with the removal of the cervix) due to reasons other than cancer should stop screening if they have no history of abnormal pap smears. – Women over 65 should stop cervical cancer screening if they’ve had three negative paps in a row or two negative pap plus HPV tests in a row within the past ten years, with the last test being in the previous five years.

Cardiovascular disease: Male sex is considered a nonmodifiable risk factor for cardiovascular disease. However, after menopause, women have greater increases in cardiovascular risk and end up catching up to their male counterparts. This seems to be at least partially due to the withdrawal of a protective effect of estrogen on different parts of the cardiovascular system.

Hormone therapy after menopause has not been shown to protect against cardiovascular disease, although there is a possibility that it is protective if started in younger women who have gone through menopause more recently.

Cardiovascular risk factors that should be addressed are high cholesterol, high blood pressure, smoking, and diabetes. This is also a great time to pay more attention to a healthy diet and begin an exercise program (with your provider’s approval) if you don’t already have one.

Colorectal cancer screening: Colorectal cancer is the third most common cancer in women and the third most common cause of cancer deaths in women. Early detection through screening can save lives. Most colorectal cancers are diagnosed after age 50, although cases in people under 50 are on the rise.

For people with average risk, the USPSTF recommends screening for colorectal cancer starting at age 50 and continuing to age 74. The American Cancer Society recommends screening for colorectal cancer starting at age 45 in those with average risk and continuing to age 74. People aged 75–84 can discuss continuing screening with their provider. Colon cancer screening should stop once people reach 85. Various screening methods are available, including colonoscopy, fecal immunohistochemistry (FIT) testing, flexible sigmoidoscopy, Cologuard, and CT colonography. Discuss with your provider which method is best for you.

A special note regarding sexual transmitted infections and HIV/AIDS

According to the Centers for Disease Control and Prevention (CDC), of the almost 40,000 new HIV diagnoses in the United States in 2016, 6,812 (17%) were in people aged 50 and older. The American College of Obstetrics and Gynecology (ACOG) reported in 2005 that older women may especially be at risk because of age-related vaginal dryness and thinning that can cause tears in the vaginal lining. These tears, even if they are too small to see, may increase the chances of transmission of HIV and other sexually transmitted infections. It is important to practice safe sex, including condom use, to decrease the risk of sexually transmitted infections even if you are no longer concerned about contraception.

IMPORTANT:

If you experience any unusual side effects, contact your Rory provider or your primary care provider. If you are having a medical emergency, call 9-1-1 or go immediately to your local emergency room. Any new symptom should be discussed with your provider. Any severe symptom should be treated as an emergency. Contact your provider after it is addressed. Again, take the time to read the list of potential side effects.

If you have any questions about this information or any other concerns, we’re here for you. Please contact your provider to discuss any questions or concerns.

Venlafaxine is recommended by NAMS for the treatment of hot flashes in dosages of 37.5–150 mg per day. In a study, venlafaxine 75 mg per day was as effective as 0.5 mg of estradiol per day at reducing hot flash frequency at eight weeks (47.6% in the venlafaxine group vs. 52.9% in the estradiol group). It is thought to work by increasing serotonin levels and restoring the ability of the hypothalamus to regulate body temperature.

Venlafaxine (please read the PDR for a full discussion)

Please read everything below. It is a summary of some of the information in the PDR and other sources. Please read the full package insert when it arrives with your medicine. You can access the PDR directly, as well. Keep all the information handy in case your medical status changes and you need to refer back to it.

What are some important things my provider should know?

– Thoughts of doing harm to yourself at any point in the past – History of mental illness in you or your family (e.g., depression, psychosis, bipolar disorder, manic depression) – Glaucoma – Irregular heartbeats (arrhythmia) – High blood pressure – All medications taken now and within the past two weeks – History of illicit drug use – History of drug addiction – History of serotonin syndrome – A list of all your current medical problems, including, but not limited to, liver disease, kidney disease, heart disease, seizure disorder, and bleeding disorders – Allergy or negative reaction to venlafaxine or other serotonin norepinephrine reuptake inhibitors (SNRI) under different names or any components (e.g., Cymbalta, Effexor, Fetzima, Pristiq, venlafaxine, desvenlafaxine, duloxetine, levomilnacipran)

If you have any of these conditions and it has not been shared with your provider, please do so now.

Why it’s important to keep all providers in the loop

Hundreds of medications can interact with venlafaxine. Most of these interactions are not severe, but some can be serious and even life-threatening. That is why we ask for a detailed history of all your medications. Even simple over the counter medications must be checked for interactions. All your providers should be kept informed of any medication that is added, dropped, or changed in your regimen.

The Prescribers’ Digital Reference (PDR) lists the medications that can interact with venlafaxine along with the contraindications to its use. The PDR is included because it is comprehensive and should be read in its entirety. Certain conditions and medications mean that it’s never safe to take venlafaxine, while others mean that the risks and benefits need to be weighed. A few relevant sections are summarized below concerning contraindications and drug interactions, but it is not a complete overview. Please also read the entire package insert that comes with your medication.

SNRIs like venlafaxine are generally safe for most people, but all medicines have the potential for causing side effects. In rare circumstances, these side effects can be serious, and you should be aware of them.

Contact your Rory provider or primary care provider if you experience any new symptoms or side effects after you begin taking your medication.

Venlafaxine has a black box warning about a potential for increased risk of suicidal thoughts and behaviors in patients aged 24 and younger. Patients under the age of 25 are not eligible to be treated with venlafaxine through Rory. Venlafaxine is most commonly used as an antidepressant, typically at doses of 150–225 mg.

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. The risk from lower doses of venlafaxine cannot be excluded.

Serotonin syndrome is a potentially life-threatening condition that can occur when people take drugs that increase the activity of serotonin in the central nervous system (CNS). This risk can be higher when two or more drugs that increase serotonin activity are taken at the same time. Drugs like venlafaxine can increase the activity of serotonin in the central nervous system.

Serotonin syndrome is characterized by elevated body temperature and sweating, muscle rigidity, diarrhea, confusion, and agitation. In severe cases, it can lead to multiorgan failure and death.

Venlafaxine also has the ability to precipitate a manic episode in people suffering from bipolar disorder. People who have bipolar disorder, manic depression, or mania should not take venlafaxine without consulting with their psychiatrist. Patients with a history of bipolar disorder, mania, or manic depression are not eligible to be treated with venlafaxine through Rory.

You should always keep all of your providers informed of all medications that you are taking to avoid dangerous drug interactions. See below for contraindications and drug interactions.

There is a condition called antidepressant discontinuation syndrome, which may occur when a patient abruptly stops taking drugs like venlafaxine. It is very rare to experience antidepressant discontinuation syndrome from stopping low doses of venlafaxine (75 mg or less). If you are experiencing headaches, nausea, dizziness, fatigue, flu-like or other symptoms after stopping venlafaxine, please contact your Rory provider and your primary care provider.

NOTE:

Pregnancy and nursing Venlafaxine for hot flashes/flushes is not recommended in pregnant and nursing women. Women who are pregnant or nursing are not eligible to be treated with venlafaxine through Rory.

Children Venlafaxine for hot flashes/flushes is not recommended in children. Venlafaxine has a black box warning for an increase in suicidal thinking in patients aged 24 and under. Patients who are under age 25 are not eligible to be treated with venlafaxine through Rory.

Venlafaxine is well tolerated by most patients. Side effects can include: Decreased sex drive or difficulty with orgasm Blurry vision Headache Nausea Insomnia Drowsiness Diarrhea Weakness Anorexia Xerostomia (dry mouth) Hyperhidrosis (excessive sweating) Abdominal pain High blood pressure Tremor Other less common side effects can be reviewed here.

Most of these side effects will resolve with continued use. Venlafaxine has been associated with weight loss in some people.

If any of the contraindications and precautions below apply to you, or if you have a medical condition or are taking any medications and you haven’t already done so, please alert your provider. You should also alert your Rory provider or your primary care provider if you experience any new or worsening symptoms or side effects.

– History of suicidal thoughts or attempts – History of self-injurious behavior – History of bipolar disorder – History of manic or depressive episodes – History of serotonin syndrome – Patients taking an SNRI for another indication like depression or anxiety. (e.g. Cymbalta, Effexor, Fetzima, Pristiq, desvenlafaxine, duloxetine, levomilnacipran) – People taking MAOIs or who have taken MAOIs in the previous two weeks – People with a history of long QT syndrome or who are taking drugs that lengthen the QT interval – People with moderate-severe liver disease. Even people with mild liver disease may require lower doses – People who are pregnant or nursing – Children under the age of 18 – People with bleeding disorders or who are taking medications that increase their risks of bleeding should discuss this with their provider before taking venlafaxine. In most cases, an alternative treatment strategy will be used.

Although SNRIs were originally designed to reduce stress and anxiety, they can exacerbate psychiatric conditions in women with a history of clinical depression and increase the risk of suicidal thoughts or behaviors. They can also cause patients with undiagnosed bipolar disorder to become manic, which is a self-destructive condition. Patients with bipolar disorder are much more likely to have depressive episodes before mania. Venlafaxine should therefore not be taken for hot flashes/flushes by patients with a history of depression unless they are being followed by a psychiatrist for depression.

Children under 18 years should never take venlafaxine or any other SNRI unless directed to do so by their psychiatrist. A study showed an increase in suicidal thoughts and behavior (but not actually suicide), and therefore the U.S. Food and Drug Administration (FDA) has issued a black box warning against children taking this medication.

Venlafaxine cannot be used with medications called monoamine oxidase inhibitors (MAOIs)—examples include, rasagiline (brand name Azilect), selegiline (brand names Eldepryl, Zelapar), isocarboxazid (brand name Marplan), phenelzine (brand name Nardil), and tranylcypromine (brand name Parnate).

In fact, venlafaxine cannot be used by anyone who used an MAOI two weeks before starting venlafaxine or who even may need it two weeks after stopping venlafaxine.

Venlafaxine also cannot be used in anyone who is on linezolid (brand name Zyvox), which is an antibiotic, or intravenous methylene blue (used to treat a rare disorder called methemoglobinemia).

Treatment Many therapies have been studied for the treatment of hot flashes/flushes. The treatments fall into four broad categories:

– Behavioral techniques – Nutritional supplements – Prescription medications, including:Hormone replacement therapy estrogen +/- a progestin – Non-hormonal, prescription medications that have been studied for the treatment of hot flashes/flushes.

Some of these treatments may not be offered through Rory. You and your primary healthcare provider should balance the benefits and the risks in the use of any medication.

Behavioral and mind body techniques Many behavioral techniques and modifications have been studied. Some have robust evidence indicating that they are effective while others have little, or weaker evidence, but are still recommended by healthcare providers because they are very safe and may help. The following are some behavioral techniques that can be attempted though there is no strong evidence of benefit.

Cooling Techniques Various cooling techniques can be tried. These include wearing layers so that they can be removed as needed, wearing light breathable clothing (e.g. cotton), keeping fans and cold water handy, using devices that cool your blanket or comforter at night, and keeping an ice pack near the bed that can be placed under your pillow as necessary.

Avoiding Triggers Some have suggested avoiding hot beverages, spicy foods, and caffeine is helpful. However, there is no evidence that avoiding them is effective. Smoking and alcohol have also been proposed as triggers of hot flashes. It is recommended that all women who smoke should quit regardless of whether it will help with hot flashes. Moderate alcohol consumption (no more than one drink per day) is also recommended as part of a healthy lifestyle.

Weight Loss and Exercise Weight gain is one of the dreaded consequences of menopause, and many women feel that their bodies are rebelling against them. The same diet and exercise regimen that kept their weight stable through the years suddenly results in added pounds. Weight loss is difficult during this stage of life and may require the help of a professional dietician.

However, several studies have shown that weight loss is an effective treatment for decreasing the severity of hot flash/flush frequency. Weight loss was also associated with a greater chance of eliminating hot flashes at one year. Furthermore, weight gain was associated with an increased risk of moderate to severe hot flashes/flushes. These studies tell us that weight loss, when feasible, should be recommended for the management of hot flashes.

Exercise is an important part of a healthy lifestyle as long as there are no contraindications. Speak to your primary care physician before starting an exercise program.

Mind Body Techniques Various mind body techniques have been studied including cognitive behavioral therapy (CBT), relaxation training, paced breathing, mindfulness-based stress reduction (MBSR), and clinical hypnosis. Of these, CBT and clinical hypnosis have the best evidence showing effectiveness.

CBT is a form of psychotherapy that aims to modify dysfunctional thoughts, behaviors, and beliefs. Two studies showed its effectiveness at improving the symptoms of hot flashes/flushes, and the improvements were maintained after 26 weeks.

Clinical hypnosis involves achieving a deeply relaxed state through imagery and suggestion from a practitioner. It has been shown to decrease the frequency and severity of hot flashes/flushes.

CBT and clinical hypnotherapy are both recommended by the North American Menopause Society (NAMS). The downsides of these approaches are the time investment and cost, and access to practitioners may be limited in some areas. They are definitely worth a try if you have the finances, time, and access to a competent practitioner.

Nutritional supplements

Phytoestrogens (Plant Estrogens) Phytoestrogens are chemicals found in plants that are similar to human estrogen. They are able to bind to estrogen receptors and produce the same effects to a greater or lesser extent. One of the foods highest in phytoestrogens is soy. Soy contains several phytoestrogens, including genistein, daidzein, glycitein, biochanin A, and formononetin. Genistein and daidzein are the two most well known of these compounds.

Soy products and supplements vary greatly in the amount and potency of the phytoestrogens in them. In addition, only about 30% of North American women can metabolize daidzein into equol, which may be the beneficial compound in soy for hot flashes. NAMS does not recommend the use of soy foods or supplements for the treatment of hot flashes, although whole soy foods are safe to use as part of a healthy diet for those who do not have a sensitivity or allergy to soy.

Black Cohosh and Vitamin E Vitamin E is an essential nutrient needed for healthy vision, reproduction, and immunity. It is a fat-soluble vitamin that is also an antioxidant. Black cohosh is a plant whose roots are used as an herbal supplement. Both have been found in several studies to be effective in the treatment of hot flashes.

Rory offers a single tablet that combines black cohosh and vitamin E, which can be used alone or in conjunction with your prescription medication. If you would like to learn more, click here.

Prescription Medications

Estrogen With or Without Progesterone (Hormone Therapy)

Systemic estrogen (doses high enough to increase blood levels) is the oldest, most effective prescription drug for the treatment of hot flashes/flushes (and other menopausal symptoms). It comes in many different forms with slightly different chemical structures.

In women who still have a uterus, estrogen should be used with a progestogen (progesterone) because estrogen alone increases the risk of endometrial hyperplasia (increased growth) and cancer. No progestogen is needed when low dose vaginal estrogen is used to treat vaginal dryness and irritation associated with menopause. In general, the lowest dose of hormones for the shortest duration possible is recommended.

While estrogen is very effective at treating hot flashes, the Women’s Health Initiative (WHI) study made many women and providers reluctant to use systemic estrogen. The study showed an increased risk of stroke and blood clots. Those who also took progesterone (MPA) also had an increased risk of invasive breast cancer. There was also a decrease in bone fractures.

Who should not use estrogen therapy to treat hot flashes/flushes?

Women with the following conditions should not use estrogen therapy:

– Unexplained vaginal bleeding – Severe active liver disease – Prior estrogen-sensitive breast or endometrial cancer – Coronary heart disease (CHD) – Stroke – Dementia – Personal history or inherited high risk of thromboembolic disease (blood clots) – Porphyria cutanea tarda – High triglycerides

If you are not a candidate for estrogen therapy or prefer not to use it, there are other prescription medications that are effective to treat hot flashes/flushes.

Why does Rory not offer estrogen therapy for hot flashes?

Due to the concerns about blood clots, stroke, and breast cancer from the WHI study, many women are not candidates for estrogen therapy. Many others are concerned about the risks associated with hormone therapy. For this reason, we have chosen to offer non-hormonal treatments that have been proven to effectively treat hot flashes.

SSRIs/SNRIs Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are drug families most commonly used to treat anxiety and depression. Nevertheless, in low doses they have proven effective in the treatment of hot flashes/flushes. The paroxetine you were prescribed is an SSRI.

SSRIs include: – Fluoxetine (brand name Prozac) – Fluvoxamine (brand name Luvox) – Paroxetine (brand name Paxil) – Citalopram (brand name Celexa) – Escitalopram (brand name Lexapro) – Sertraline (brand name Zoloft) – Vilazodone (brand name Viibryd) – Vortioxetine (brand name Trintellix)

SNRIs include: – Venlafaxine (brand name Effexor) – Desvenlafaxine (brand name Pristiq) – Duloxetine (brand name Cymbalta) – Milnacipran (brand name Savella) – Levomilnacipran (brand name Fetzima)

Several of these drugs have been found effective for the treatment of hot flashes/flushes. One study showed that the SNRI venlafaxine (at 75 mg per day) and low dose estrogen (0.5 mg of beta-estradiol per day) were equally effective at reducing hot flash frequency at eight weeks (47.6% in the venlafaxine group vs. 52.9% in the estradiol group).

Although several SSRIs and SNRIs have been found to be effective at treating hot flashes, only paroxetine 7.5 mg is FDA-approved for this indication. This preparation can be expensive, and NAMS recommends using paroxetine in doses of 10–25 mg per day as a more affordable option of treating hot flashes. While any medication can have side effects, these medications are taken in low doses and are relatively safe. Also, they can be used in women who have contraindications to estrogen or who choose to avoid hormone therapy.

Other prescription therapies

Gabapentin (brand name Neurontin) and pregabalin (brand name Lyrica), collectively referred to as gabapentinoids, have been found effective. These drugs are technically anti-epileptics (seizure medications) but are more commonly used for different types of nerve pain. They are not frequently used for treating hot flashes/flushes due to their side effects (dizziness, drowsiness, headache, fluid retention, etc.).

Clonidine, a central-acting alpha-2 agonist (which means it works in the brain), is also effective at treating hot flashes/flushes but is less effective than SSRIs, SNRIs, and gabapentin. It is rarely used due to side effects (low blood pressure, lightheadedness, headache, dry mouth, dizziness, sedation, and constipation).

Contraindications and precautions for paroxetine

The following is a partial list of contraindications for paroxetine. Please, see the PDR for a comprehensive list. Additionally, if you have any of the below conditions and have not already done so, please inform your provider.

Sensitivity or Allergies: Patients with sensitivity or an allergy to paroxetine in any form or to any other ingredients in the formulation cannot take paroxetine.

Kidney Issues: Dose adjustments should be made for those with severe kidney impairment or issues. Decreased doses are needed as kidney impairment slows the clearing from the body of paroxetine. The exception to this is for people taking the 7.5 mg dose of paroxetine for which no dose adjustment is necessary.

Liver Issues: Dose adjustments should be made for those with severe liver impairment or issues. Decreased doses are needed as kidney impairment slows the clearing from the body of paroxetine. The exception to this is for people taking the 7.5 mg dose of paroxetine for which no dose adjustment is necessary.

The elderly: Patients over 65 are at higher risk of experiencing side effects when taking paroxetine, including balance and gait issues, sodium deficiency, fainting, cognitive impairment, dementia, and lower urinary tract symptoms and benign hyperplasia in men. Due to the increased risk in this population, members who are over 65 are not eligible for treatment with paroxetine through Rory.

Dehydration: SSRIs, like paroxetine, may cause hyponatremia (low sodium levels), which is frequently the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). People over 65 and those taking diuretics are at higher risk for this. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of the SSRI, as well as implementation of the appropriate medical interventions.

Pregnancy: Paroxetine is contraindicated in pregnancy for the treatment of hot flashes.

Breastfeeding: Paroxetine should be used with caution in breastfeeding women.

MAOI therapy: Paroxetine cannot be used with medications called Monoamine Oxidase Inhibitors (MAOIs)—examples include, rasagiline (Azilect), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate).

In fact, paroxetine cannot be used in anyone who used an MAOI two weeks before starting paroxetine or who may need it two weeks after stopping.

Paroxetine cannot be used in anyone who is on linezolid (Zyvox), which is an antibiotic or intravenous methylene blue (used to treat a rare disorder called methemoglobinemia).

Bipolar disorder, mania: Paroxetine can precipitate a manic episode in patients with bipolar disorder. It should not be used in these patients for the treatment of hot flashes/flushes unless under the direction of a psychiatrist.

Seizure Disorder: Paroxetine should be used with caution in patients with seizure disorders. It is generally avoided for the treatment of hot flashes/flushes in patients with seizure disorders.

Anticoagulant therapy, bleeding, thrombolytic therapy: SSRIs, like paroxetine, can increase the risk of bleeding especially in those with a bleeding disorder in those taking medications that increase the risk of bleeding (e.g. NSAIDs, aspirin, blood thinners).

Bone fractures, osteoporosis: Studies have shown an association between the use of SSRIs, like paroxetine, and the development of bone fractures. It is not known if the SSRI exposure was the cause of these fractures. Caution should be used in patients who have osteoporosis. If you have concerns about osteoporosis and bone fractures please speak with your provider.

Closed-angle glaucoma, increased intraocular pressure: Caution is recommended when prescribing paroxetine to patients with closed-angle glaucoma because the pupillary dilation that can occur with antidepressants may precipitate a closed-angle glaucoma attack in susceptible patients.

Akathisia: The use of paroxetine or other SSRIs has been associated with the development of akathisia, which is characterized by a sense of restlessness and agitation associated with an inability to sit or stand still and feeling distressed. This occurs most often in the first few weeks of treatment. Discontinue paroxetine if akathisia occurs.

Anorexia nervosa: Decreased appetite and weight loss have been observed during administration of SSRIs. Paroxetine should be used with caution by patients with anorexia nervosa or other conditions where weight loss is undesirable.

Driving or operating machinery, ethanol ingestion: Paroxetine may affect your ability to drive. Don’t drive or use machines unless you are sure you’re not affected. The PDR recommends avoiding alcohol while taking paroxetine although there is no known, specific drug interaction.

The list below is long and no drug on the list is meaningless. That is why your provider needs to know every drug you take and every healthcare provider needs to know you take venlafaxine.

The following is a list of the most common medications that have serious interactions with venlafaxine. Please note that this list does not include every medication that interacts with venlafaxine. Please, see the PDR for a comprehensive list.

Drugs that increase the risk of bleeding Venlafaxine can increase the risk of bleeding when used with other drugs that increase bleeding risk. This includes blood thinners (e.g. warfarin, Xarelto, Eliquis, Savaysa), aspirin, other drugs that affect platelet function (e.g. Plavix, Prasugrel, Brilinta) and NSAIDs (e.g. Aleve, naproxen, Motrin, ibuprofen).

Drugs that increase serotonin levels or activity in the body

There are many drugs in this category. This is why it’s extremely important to tell every provider about all of your medical conditions and all medications, herbs, and supplements you are taking. Some examples include:

Most antidepressants (SSRIs, SNRIs, TCAs, and MAOIs) Narcotic pain medications (e.g. morphine, oxycodone, oxycontin hydrocodone) Some cough medicines (e.g. Delsym, Nyquil, Dayquil, Tylenol Cold and Flu) Some migraine medicines (e.g. Imitrex, Zomig, Frova, Maxalt) Some nausea medicines (e.g. Zofran) Recreational drugs like cocaine and MDMA (aka ecstasy, Molly) Some herbs like St. John’s Wort and many others Drugs that affect the metabolism of venlafaxine

There are many drugs in this category.

As you can see, there are many drugs that interact with venlafaxine. See the PDR for the very comprehensive list of drug interactions, and make sure that every provider has a full list of your current medications.

IMPORTANT:

If you experience any unusual side effects, contact your Rory provider or your primary care provider. If you are having a medical emergency, call 9-1-1 or go immediately to your local emergency room. Any new symptom should be discussed with your provider. Contact your provider after it is addressed. Again, take the time to read the list of potential side effects.