Menopause & perimenopause

Antidepressants for menopause symptoms: pros and cons

by Dixie Mills, MD

With the downsides of hormone replacement therapy now widely known, menopausal women and healthcare providers short on time (and often patience) are turning to antidepressants to ease hot flashes in menopause. Such a simplistic, one-size-fits-all approach may be enticing for all of us… except that menopause is not a mental health disorder.

And this is not the 1950’s — a time when women were widely given Valium to “fix” their moods and anxieties. We at Women to Women feel the fact that so many women are now being prescribed antidepressants for their menopausal symptoms is sending a very negative message: that this is a time in your life subtly surrounded by depressive factors that you cannot avoid, and by taking a pill to make one factor go away, you can make them all go away.

Using antidepressants to treat the symptoms of menopause may be one way for your doctor to help you feel better quickly and easily, which, after all, is his or her job. But, apart from how women feel about this “magic bullet” approach, we’re concerned about whether treating menopausal symptoms with antidepressants is safe — or even effective. We want to know what the side effects are for off-label use of antidepressants in menopause, and how this treatment will affect women now and in the long run.

To us, a large part of the women’s movement has always been about choice, and when it comes to women’s health, the best way to make the best choices is to stay as informed as possible. So let’s look at the antidepressants commonly prescribed for menopausal women today, how they actually work in your body, whether they are safe and effective for your symptoms, and how you can achieve similar — or even superior — results naturally.

Which antidepressants are prescribed for menopause?

There are four main types of antidepressants: tricyclics, MAOI’s, SSRI’s and SNRI’s. Antidepressants from the classes of medications known as SSRI’s (selective serotonin reuptake inhibitors) and SNRI’s (serotonin and norepinephrine reuptake inhibitors) have been found to relieve hot flashes in some clinical trials. They also conveniently “treat” the mood fluctuations that can arise during menopause. Some antidepressants have been approved, and their brand names changed, to be marketed to women for PMS and PMDD. But the FDA has not yet approved any of these drugs for the treatment of menopausal symptoms such as hot flashes, mood changes or insomnia.

Healthcare practitioners who prescribe antidepressant drugs for hot flashes are doing so “off-label,” meaning that the FDA has not approved them as either safe or effective for treating hot flashes. Although this raises a host of ethical questions, doctors routinely and legally prescribe them as the FDA does not consider off-label prescriptions (except for controlled substances) to be unlawful. There are several antidepressants currently being prescribed off-label to treat symptoms of menopause, but the ones most commonly used are:

• SSRI’s:

fluoxetine (Prozac)

paroxetine (Paxil)

and

• SNRI’s:

venlafaxine (Effexor)

There is also an SNRI antidepressant being developed specifically for menopausal symptoms called Pristiq. This drug is currently in the process of receiving approval from the FDA.

Pristiq — the menopause antidepressant

Pristiq is the trade name for a chemical compound known as desvenlafaxine succinate, which is a metabolite of the active ingredient in Effexor (venlafaxine). Its developer and manufacturer, Wyeth Pharmaceuticals, is awaiting FDA approval for its use for depression and vasomotor symptoms of menopause, particularly hot flashes and night sweats. (You may find it revealing that Effexor, also made by Wyeth, will lose its patent and therefore its profitability in 2010.) A recent decision by the FDA postponed approval of Pristiq until more information on the long-term (or at least one-year) side effects of the drug are known.

A few short-term clinical trials, sponsored and paid for by Wyeth, have been conducted on both men and women with depression, and on women with menopausal symptoms to test Pristiq’s effectiveness against hot flashes, night sweats and mood disturbances. One study recently reported that Pristiq showed a reduction in hot flash frequency from 11 to 5 per day. However, women taking the placebo showed almost the same reduction, and there was no significant benefit to Pristiq on depressive symptoms. This study has not yet been published, and was just presented at a gynecology conference.

By the way, attending conferences is one of the ways drug companies try to get their message out to doctors with the potential to prescribe their medications to women, and unless the doctor reads the fine print, he or she may not be aware that the study has not been peer-reviewed by unbiased researchers. These conferences also house multiple booths with an excess of “freebies,” including pens, water bottles, and key chains with logos on them. While doctors deny this influences their practices, studies have shown it does, and the bottom line is: why would the pharmaceutical companies spend the money if they weren’t seeing a reward?

Our view is that Pristiq may well receive approval soon from the FDA for menopause — probably for depressive symptoms first — but that doesn’t change the fact that it is an antidepressant that will be prescribed around the country as a homogenized way of treating the symptoms of menopause, when we know that every woman’s menopausal experience is different.

How can an antidepressant help menopausal symptoms?

Here’s how each of the two main groups of antidepressants achieve their effects.

Selective serotonin reuptake inhibitors (SSRI’s) Serotonin (or 5-HT) is a well-known and very complex neurotransmitter which regulates — among other things — mood, sleep, appetite, and body temperature. SSRI’s increase the efficiency of serotonin by blocking its reuptake at the nerve endings. “Reuptake inhibition” means that after serotonin transmits messages between brain cells, and it is reabsorbed into nerve endings to await recycling, SSRI’s like Prozac, Paxil and Zoloft block this recycling, allowing the serotonin molecule to remain available in the presynaptic space, or area between nerve cells, thus able to regulate body temperature and carry messages that control moods and emotions. One cannot just take supplemental serotonin for this effect because it does not pass freely over the blood-brain barrier.

Serotonin-norepinephrine reuptake inhibitors (SNRI’s) SNRI’s were developed more recently than SSRI’s, and are different in that they function in a compound fashion: they treat depression by inhibiting the reuptake of serotonin, but also of norepinephrine, a stress hormone that regulates attention, focus and the body’s ability to respond physiologically to stress. Increasing the amount of norepinephrine is thought to help with neuropathic discomfort and also temperature control, so inhibiting the reuptake of both serotonin and norepinephrine, like the SNRI drugs Effexor, Zyban, and Cymbalta do, may alleviate many menopausal symptoms at once: body temperature, hot flashes, emotional stress and nerve pain.

In the body, the naturally occurring chemicals called neurotransmitters regulate electrical signals between our nervous system and other types of cells — they are, in essence, the “messengers” of information between the brain, the spinal cord, and the remainder of the body. Neurotransmitters govern numerous activities in our bodies, including temperature regulation.

So how does this relate to hot flashes and night sweats? Because the cause of hot flashes (and how they occur) is not yet clearly understood, there is still a fair bit of hand-waving going on. One theory is that a decrease in estrogen during menopause may disrupt the balance of serotonin, a neurotransmitter in our brains. Serotonin may be involved in regulating temperature, and this disruption reportedly causes confusion between what the brain registers and what is actually occurring in the body.

You might think of it like a thermostat in your house. The thermostat (the hypothalamus in your brain), receiving improper signals, thinks the house (your body) is too hot and tries to cool it down. In our bodies, the result is the profuse sweating and release of heat we experience during a hot flash.

Antidepressants artificially allow more of the brain’s neurotransmitters — specifically the monoamines like serotonin and norepinephrine — to reach key receptors in the brain, which may allow the hypothalamus to rebalance itself.

By itself, the notion of reducing your hot flashes may sound like a miracle, especially if you have a severe case. The challenge is to learn as much as we can about how both SSRI’s and SNRI’s might react with our unique bodies. So much is still unknown, though some researchers are looking to find a genetic basis and devise a test to see which people can truly benefit from SSRI’s. It is important to understand that when used for treating your menopause, the best antidepressants can probably do is mask your symptoms. These drugs are not “cures” for a “disease,” and there is not only a controversy over their efficacy, but also over side effects and possible long-term complications.

How effective are antidepressants for menopausal symptoms?

Several studies done in recent years have spawned doubt about the effectiveness of antidepressants, largely because a great many subjects experienced the same physiological effects from taking a placebo as those taking the actual antidepressant. A 2002 American study concluded that the difference between antidepressants and placebo was “close to negligible.” In fact, in over half of FDA trials, the effects of antidepressants on people suffering from depression could not be distinguished from those who had been given a simple sugar pill.

A 2006 meta-analysis identified ten studies on antidepressants for menopausal symptoms, but only two of the ten studies were of good quality. Those two lasted a mere four to six weeks and showed only modest improvement in the number of hot flashes subjects experienced; moreover, there was a significant fall-out rate — most likely due to side effects. A couple of the fairly rated studies were done with women who had breast cancer or who were at high risk, and a recent report on this population found again only modest reduction in hot flashes with venlafaxine (Effexor). Taking this SSRI pill long term was not worth it for many women due to side effects.

So if your healthcare professional is recommending that you take an antidepressant for your hot flashes, or if you reach the pharmaceutical counter at your local drugstore and “discover” that your doctor has written you a prescription for an antidepressant (which has happened to many of our Women to Women clients!), we suggest you ask more questions. We simply do not have enough evidence pointing to antidepressants as the best way or even a way to treat your hot flashes at all, and recommend careful consideration when it comes to filling this prescription. The last thing you want to do is begin taking an antidepressant which may not even help at all, yet cause adverse side effects and perhaps lead to long-term consequences.

Should I take antidepressants if I’m not depressed?

Women in menopause and perimenopause can experience changes in mood and emotions, sometimes deeply and profoundly. Nevertheless, it’s important to understand that if you are at the age for menopause and are feeling down, you’re not necessarily clinically depressed. This is relevant because antidepressant drugs were developed by pharmaceutical companies and approved by the Food and Drug Administration for patients with major depression and other mental health conditions — not for menopausal symptoms, nor even for mild depression, anxiety, or feeling blue.

I will admit that I have prescribed Paxil and Effexor (although I could never spell it right) for some of my breast cancer patients. Many of them had been on HRT and, after going off it with their diagnosis or being thrown into menopause by chemotherapy, were truly suffering with hot flashes and lack of sleep, and could not take any estrogen. They weren’t clinically depressed and questioned me about going on an antidepressant, but (now I realize rather naïvely) I told them it was a low dose and didn’t have many side effects.

Well, I think I succumbed to the false hope that there would be an easy fix. They had just been diagnosed with a life-threatening disease, and it seemed like too much to suggest they try some lifestyle changes. But for most of these women, I don’t think that the pills really helped. Now I did not conduct a random, double-blind placebo-controlled study of my patients, but my experience showed me that they didn’t work for the majority of my patients, and most of them discontinued the medication soon afterwards.

I probably should have figured that out, as I had seen some of my breast cancer patients who were on antidepressants before diagnosis, and these drugs didn’t seem to help their symptoms afterwards either. I also didn’t realize the possible severity of antidepressant side effects.

What side effects might I experience if I take antidepressants in menopause?

Regardless of the reason for taking antidepressants — whether to treat depression, as the approved purpose of the drug intends, or “off-label” for menopausal symptoms — both SSRI’s and SNRI’s are known to produce side effects. These include headache, nausea and vomiting, sexual dysfunction and anxiety, all of which can range from mild to severe, depending on how your body responds to the drug. (Click here for a list of antidepressants and their potential side effects.)

But with regard to taking antidepressants specifically for menopause, I want to talk about venlafaxine (Effexor), now being widely prescribed around the country. Reported side effects from taking venlafaxine include an increase in blood pressure, adverse lung reactions, and even heart failure. I mention this separately because it’s especially pertinent to Pristiq, which again, is chemically very similar to Effexor. So if Pristiq is indeed the first antidepressant approved for treating menopausal symptoms, we strongly recommend speaking with your healthcare professional about its relationship to Effexor and its possible side effects, both during and after discontinuing treatment with the drug, especially if you have high blood pressure or a history of heart trouble.

Another side effect of antidepressants often overlooked is their impact on the sleep cycle. Virtually all major antidepressant drugs suppress REM sleep, especially SSRI’s. This means that although your hot flashes and night sweats might be treated with an SSRI, there’s a good chance that if you’re on the drug, your body still won’t be getting the kind of deep rest it needs. And we all know that not giving your body enough rest can bring on a whole host of system-wide problems.

If your menopausal symptoms are severely impacting your quality of life, then it may be reasonable to consider the option of using antidepressants to treat them. But because there is always a risk in introducing a new drug to your body, if you suffer mild to moderate hot flashes, you may wonder whether exchanging hot flashes for fatigue, nausea or anxiety is worth it, especially when considering the possible long-term effects of taking antidepressants. Though modern antidepressants do not evoke as many side effects as the older ones do, they all have a side effect profile. In addition, many people, once stopping the drug, do suffer withdrawal symptoms — so an important part of deciding whether or not to take antidepressants for menopause is to examine not only what might happen to your body during treatment, but also during the months and years after stopping the drug.

Antidepressants for menopause and dependence

Answering the question of whether or not antidepressants are addictive is not easy, and depends on how we define “addiction.” Although antidepressants aren’t addictive in the sense of opium narcotics or nicotine — they don’t cause uncontrollable urges to increase or ingest more of the dose — many doctors and people who have taken them report that the drugs can be dependency-inducing and that all have some type of withdrawal syndrome. Some users are beginning to sue the makers of certain antidepressants for not being forthcoming about the risks for dependency.

Withdrawal is one of the biggest reasons we believe it’s not a good idea to begin taking antidepressants, unless your symptoms are severe and there are no other working alternatives for relief. The majority have some minor symptoms like headaches and dizziness — similar to going cold turkey from caffeine. However, a smaller percentage but significant number have more serious side effects such as panic attacks, tremors or shakes, intractable tinnitus (ringing in the ears), gait problems, and disorientation.

On top of the physical symptoms, there is also the possibility of psychological need to continue the drug. It makes sense when you think about it: if you take an antidepressant without being clinically depressed, in effect you’re inducing the same mood-altering reaction you would if you were indeed treating depression. Antidepressants may alleviate your hot flashes and night sweats, and may make you feel temporarily “happier,” but when the time comes to stop the drug, even just six to nine months later, the longing to feel emotionally the same as you felt while on the drug could linger.

For many women, this lingering can become a physical need that’s quite powerful — enough to severely affect their daily lives. The term thymoanesthesia directly refers to this — the phenomenon of emotional numbness or mood anesthesia, and many users of SSRI’s and SNRI’s complain of apathy, lack of motivation, emotional numbness, feelings of detachment, and indifference to surroundings, along with a feeling of just “not caring about anything anymore.”

SSRI’s, in fact, if suddenly discontinued, may produce somatic and psychological symptoms so severe there is now a medical name for it: SSRI discontinuation syndrome. There is even a mnemonic — FINISH — to remember the symptoms: Flu-like, Insomnia, Nausea, Imbalance, Sensory disturbances, and Hyperarousal.

So even if your hot flashes last just a few months, treating them with antidepressants could mean that you’ve got to cope with coming off of the antidepressant afterward. Most healthcare agencies now advise at least four to five months of continuation treatment with antidepressants to see the effect, by which time the majority of people would be subject to suffer withdrawal symptoms. Likewise, primary care offices (where SSRI’s are most commonly prescribed) are now becoming aware of these symptoms and are more knowledgeable about tapering doses to reduce the side effects.

We need to keep in mind that this kind of “weaning” off antidepressants may only reduce the severity of a discontinuation reaction — it may not prevent it. And although most cases of discontinuation syndrome last only between one and four weeks, there are examples of patients experiencing adverse effects such as impaired concentration, poor short-term memory, elevated anxiety, and sexual dysfunction for not just months but even years after discontinuation.

How did we get here?

Drug companies spend millions of dollars on research and development of new drugs. For FDA approval they need to provide safety and efficacy results. The drug company, with a vested interest, runs a clinical trial usually for a short time, sometimes a few weeks or maybe six months but rarely more than a year. Their new drug merely has to work as well as the standard drug it is being compared to. Sometimes the drug is compared to a sugar pill to be sure it is safe and that there are no severe side effects.

Once the drug is approved, marketing wizards take over, the ads are plastered on TV, in the magazines, and on the internet, and then the journalists get in the thick of things too, for better or worse, and spin the drug for good or bad. Many doctors rarely read the original study on the drug’s effectiveness — but they are given free samples, free lunches, free pens, and fancy brochures about the latest and greatest new drug.

Since 1997, drugs companies have been allowed to directly advertise to the public (prior to that ads were only placed in medical journals). But it’s still illegal to advertise a drug for an indication that the FDA has not approved. So one can see that the drug companies have resorted to a different level of promotion — word of mouth, which we know from playing the game “telephone” as children, may set us up to lose important information.

We understand that transitioning through menopause can be a major life challenge — we know that there are good days, bad days, and everything in-between. We know, too, that the experience is not merely a physical one. It’s not just about hot flashes and night sweats; there is a very powerful emotional shift taking place in your life, as the way in which you now view yourself — and the way in which women at menopause are viewed at large — is changing. We also recognize that there’s a lot to think about before a woman decides to take antidepressants for hot flashes and other symptoms of hormonal imbalance, as the efficacy and potential side effects of these drugs, short and long term, carry real risks. The good news is that we also know that there are other, much healthier options for finding relief from your symptoms.

Achieving relief for menopausal symptoms — naturally

Simple lifestyle and diet changes can so often achieve the same or similar effects as an antidepressant, and will certainly improve your overall strength and wellness. For specific ways to treat your hot flashes naturally — with a nutritional plan that includes quality micronutrients; omega-3’s to help with inflammation, depression and anxiety; and information on creating hormonal balance such as that we offer in our Personal Program — see our article on hot flashes and night sweats.

In addition, we all know that aerobic exercise increases energy reserves and helps prevent not just depression, but also high blood pressure, obesity, heart disease, insomnia, and some types of cancer. Exercise benefits the nervous system in many ways, too, increasing blood flow and oxygen to the brain; increasing growth factors that help create new nerve cells, and increasing the chemicals in the brain that promote cognition. Regular exercise releases serotonin, which is where the notion of a “runner’s high” comes from, enabling us to achieve much the same effect as an antidepressant, but naturally.

Here is where exploring pleasure can fit in. Menopause can certainly be a time to reevaluate and reclaim certain joys that may have been forgotten in the midst of career and family demands. Stay tuned for more of this in an upcoming article on menopause and filling the empty nest.

Looking for a lifestyle change rather than a “fix” might not be as quick and easy for your healthcare practitioner, but if you are in perimenopause or menopause with mild to moderate symptoms, we strongly encourage you to try the natural route.

Where to go from here

We have all been shown thousands of images of our society’s view of the cheerful 1950’s housewife, but where we once might have felt pressured to be like her, we may now on some level feel sorry for her. If her culture prohibited her from experiencing and openly celebrating her menopause as we now can, she could not have realized that her symptoms were integral to this normal and natural process of her life, caused by a normal fluctuation and resetting of hormones within her body — she was merely given a pill and told, “Take this. You’ll be fine.”

At Women to Women, we understand that the symptoms of menopause are not just about the body; nor are they “all in your head.” Using antidepressants to treat menopause symptoms may be one option for some women, and can be used as part of a comprehensive wellness strategy. But using antidepressants without understanding how they work in our bodies, or how they are affecting our process of menopause, isn’t bringing us any closer to the kind of self-knowledge we need to achieve a deep and long-lasting foundation of health during this important transition in our lives.

Related to this article:

References & further reading on antidepressants in menopause

Original Publication Date: 10/02/2007
Last Modified: 02/16/2010
Principal Author: Dixie Mills, MD, FACS