Tamoxifen and Antidepressants

I just received this as part of my Advocates weekly e-mail and thought it might be of interest. I had hearad about this prior but paid it no mind until this latest article. I wonder if arimidex supports this same claim?
Antidepressants may reduce tamoxifen's benefits
Antidepressants used to treat hot flashes in women taking the breast cancer drug tamoxifen may reduce the effectiveness of the tumor-fighting medication, U.S. doctors said on Tuesday. Their study, published in the
Journal of the National Cancer Institute, also offered a possible explanation for why tamoxifen works better in some women than others.
"Our study suggests that tamoxifen's metabolism, and possibly its effectiveness, can be modified by the genetic makeup of the person taking the drug and by the use of another drug prescribed to reduce tamoxifen-related hot flashes," said David Flockhart of the Indiana
University School of Medicine, who led the study.

Up to 80% of women taking tamoxifen, which helps block the effects of the hormone estrogen, experience hot flashes as a side effect.
Antidepressants in a class called selective serotonin reuptake inhibitors are often used to treat the hot flashes. Flockhart's team tested the SSRI Paxil. SSRI drugs are known to interfere with the enzyme that breaks down tamoxifen into active anticancer agents called metabolites, including 4-hydroxy-tamoxifen, believed to be tamoxifen's most active breakdown product. Looking at the study subjects' blood, the researchers discovered a previously unknown metabolite they named endoxifen that also appears to have significant anticancer activity.
However, in the women taking Paxil, endoxifen concentrations fell anywhere between 24% and 64% when compared with levels in women not taking the antidepressant. The study included only 12 women, so more research is needed to show whether taking antidepressants reduces the benefits of taking tamoxifen, the researchers concluded.

Sorry, that first bit applied to Remeron, not Elavil. I did read them at
2am. The rest of it was however what it says.
How it is classified in various databases is rather irrelevant to the question.

The question was whether it would interfere with Tamoxifen. The research on paroxetine had suggested that drugs which inhibit the re-uptake of serotonin might interfere with the mechanism of Tamoxifen. The research on Elavil suggests that it does inhibit the re-uptake of serotonin, whether or not that is its main mechanism of operation. Therefore there is the possibility that there might be an interaction.

Remember that this is not a proven problem anyway, just a possible interaction that needs investigating; and all I am saying is that this drug is not proven to be excluded from the issue.

<< Yes I did post the aforementioned post. With Webtv, we can smallify with our own "thingees" so we don't have to be concerned with what will

First to J and Bea, please excuse the misquote.

<< Onc that he can't use the Tamoxifen on me due to my being
Herp2+ and ER+. So.....it's Arimidex for me soon as I complete my radiation treatments...Kaye said she is on it and isn't having tremendous problems so far. I will "try" to keep a positive atitude about it and maybe I can do well on it too. >>

After a few months on it I did start feeling 'arthritic-like' stiffness in my knees and elbows but Celebrex took care of that.

posting inaccurate information. Thank you Kaye, Tim and Bea for correcting my mistakes. - Tony >>

s'okay. I do the same, but I could get in 'trouble' (in my profession) if I didn't know something about this area
One area that is often not researched in depth involves drug interactions. Not all can be evaluated--just too many out there and not enough resources to evaluated each. In addition different people respond differently and there may not be a large enough sample to get valid data.

Elavil (Amitriptyline ) probably classes as an SSRI but its classification appears disputed. Here is what RxList has to say

"Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.
Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline."

from http://www.rxlist.com/cgi/generic/amitrip_cp.htm

I ought to put RxList on our FAQ links page, it is quite handy for this sort of thing.

This list also says that Remeron is not an SSRI. and appears to be in a class on its own.

Tim, I have great respect and appreciation for your responses because you seem to understand quite a lot about bc. However, I am confused by the above post about the Arimidex..

First f all, I am post-menopause by age and due to a partial hysterectomy in my 30's. But when I asked my Onc why he was not giving me the Tamoxifen, unless I misunderstood him, he seemed to indicate it had to do with my being positive on "both" the Her and ER thing. I feel so stupid because I really don't understand all this stuff. The radiologist doctor was the one who told me it was unusual for a bc patient to be both Herp2+ and ER+.

Are you stating that you think (in your opinion) that I could still take the Tamoxifen? and that the Arimidex would be the wrong drug for me?
Tamoxifen has been around longer and I was beginning to adjust to the idea of it when he told me it had to be the Arimidex. Maybe I should get a second opinion before I go 5 years on the wrong drug! Any advice you can give me will be greatly appreciated. Thanks!

I understand that in order for a study to be deemed successful, you need more than 12 people! For some reason at least 2500 sticks in my mind. The more you have, the better the study results.

Thanks so much for the webpage on the Arimidex, Tim. Your post sure saved me from doing a lot of research today and is a great education for me on this stuff!

If you are a doctor and ever put up a practice in my neck of the woods,
I would be seriously considering being your patient (that's "if" you were on my medical plan). I don't know what medical school you went to but I bet even our Su-Texas would have to give it a thumbs up if it turns out students and doctors like yourself. My heartfelt thanks to you and all the other posters on here who have shared their wealth of bc knowledge with me.

Thank you Kaye for some excellent insights. However, I feel that the patient (in this case, myself) should have the right to decide what they consider their quality of life should be. As I experience it now in the US and the medical profession, "they" seem to take that power away from me by trying to impose drugs on my body which I may not be able to withstand. BTW....poor Dr. Kervorkian is spending his last days in prison when all he tried to do (in my opinion) was allow people to decide when they had had enough suffering. A dog would be put out of it's misery but man must be allowed to be tied to tubes so he can stay
"alive".

Thanks for the additional info Kaye. Are you Her2+ and ER+ too?? Also can you tell me if Tamoxifen and Arimidex are both called "aromatase inhibitors"? (I will research what an Aromatase inhibitor is tomorrow).
I am so uneducated in this stuff but do want to learn what I can to make sure I get the best help for myself. My problem is that I can't take
Celebrex or any anti-inflammatory type drugs due to an ulcer and stomach problems so I will be in a fix if the drug I am given triggers off joint pain.

Thanks for any additional info you may be able to give me.

J wrote << So like I see it.....we either have a choice of letting the cancer destroy our lives or living a few years longer in misery and depression with Tamoxifen. "Quality" of life has got to have some meaning even for bc patients.>>

Okay, I don't see it that way at all. I am not depressed. Yes I do have hot flashes, but they have gotten better. What worsens them is everytime I eat any food with sugar. It's almost a given that a hot flash will soon follow. I don't miss giving up as much sugar as I used to consume. I don't miss it at all. I do choose my sugared foods more selectively, though. That has not affected the quality of my life. It has made it even better. I would much rather savor the taste of one small piece of dark Godiva chocolate that a bunch of other sugary desserts.
Also, latest research reports indicate that exercise improves depression as much as if not more than antidepressants. I don't know if it does or doesn't since I began crash exercise at time of my diagnosis--ONLY to change the state of my body at that time. I had no idea what I was doing or whether or not it would help. I do get angry about having b.c. but I am channeling that anger into doing as much as I can about it. I am not feeling sorry for myself. I don't have time to feel 'sad'---overwhelmed at times, but not sad.
Oh, and I am taking Arimidex. It started to result in stiff joints but that improved when I started Celebrex. If ever Celebrex bothers my stomach--which I don't think it does--but the Doxycycline sometimes does--I drink aloe vera gel which I get at the health foods store. I expect to need several glasses of it--but am amazed that taking one glass of about w to 4 oz of it mixed with about the same amount of grape juice, the problem goes away. So, I can say that the Arimidex has not yet affected the quality of my life after taking it regulary for 22 mos.
I am doing what I can to survive. That has given me a sense of enpowerment that I never expected. I have no clue if it will help but as many of you know

she gave me all her reasons. I told her I was choosing not to take it. She was not forceful, and ask me at the next few visits if I had changed my mind. I continued to tell her no, that for me, I did not feel it was an option. She respected my right to make that decision for myself. I do not feel my decision is for everyone, this is strictly a personal choice.>>

I feel the same. I also refused Tamoxifen; however, at the time it was the only way I would be offered an aromatase inhibitor which according to most recent research was the better of the choices, particularly since I am Her2+

I do want to state that I feel my doctor was doing her job by making her suggestion and giving me her reasons for her decision >>

I'm surprised the RXlist puts Elavil in the category of an SSRI. The info I read stated that the SSRIs did not come on the market until quite some time after the older tricyclic type antidepressants (which I thought Elavil was). That could be why it is in dispute that Elavil is actually an SSRI.

Thanks for the info on Remeron. I thought it was an SSRI since I also thought it was one of the newer drugs. I just recently heard about it.

BTW, I think it is a good idea to put the RXlist on the FAQ page. The good old "everything in one place" type thing comes in real handy.
Thanks for the info.

<>

I had also read this. I dunno about whether or not effectiveness of Arimidex would be effected or not; however, it acts/responds differently than Tamoxifen.
Still, the effectiveness of most medications and efficacy with other medications has not been evaluated, and there is always the potential for them to have some effect--either positive or negative.

Sorry, I am strictly an amateur at this. I think I am too old to consider starting a new profession. In my day job I am a "machine doctor", a freelance diagnostic engineer in industry. My medical knowledge is entirely learnt from having nursed my late wife through all the stages of this disease.

Not at all. As you are post menopausal then an aromatase inhibitor would probably be the drug of choice from the viewpoint of minimising cancer risk, but the long term side effects are less well understood. I was surprised that the HER2 status was the deciding factor, but I suppose it makes sense.
Yes it indicates a reduced effectiveness for Tamoxifen, but I don't think it is yet proven that it does not do the same for Arimidex. I think the main reasons for Tamoxifen being most commonly prescribed in this situation are low cost and long track record.

With regard to your question about aromatase inhibitors in the other post,
Tamoxifen is not an aromatase inhibitor. It attaches to estrogen receptors but unlike estrogen does not stimulate cell growth, and so it blocks estrogen from working. The biological effect does appear to be somewhat different from removing estrogen altogether. The aromatase reaction is the method by which adrenal hormones are converted to estrogen around the body in fat, muscle etc, outside of the ovaries. Aromatase inhibitors block the production of the enzyme aromatase and so prevent estrogen being produced by this pathway. As the ovaries produce estrogen by a different chemical route, this is only useful if the ovaries are non-functional. The aromatase pathway is particularly significant in people of high body mass.

See the "about arimidex" page at www.arimidex.com, http://www.arimidex.com/1000_about/1020_how.asp and watch the little animated description.

If the particular drug causes unmanageable side effects, there are alternative possibilities, reverting to Tamoxifen would be an option.

Am I missing something here?

As far as I know HER2+ and ER+ doesn't contra-indicate Tamoxifen.

The indication for Arimidex should be being post-menopause as indicated by blood test (or deliberately induced). That implies that all estrogen is being produced by the aromatase reaction and so will be effectively blocked by Arimidex.

(Prozac is one) work by inhibiting MAO. >>

The first sentence is correct. However, Prozac is a relatively new antidepressant. It was the first of a new class--SSRI's to be developed. It came out about 1987.
Here's some info on it: http://www.activeliferx.net/pages/prozac.html
"Prozac
About Prozac
Prozac was first approved by the FDA (Food and Drug Administration) in 1987.
Prozac is manufactured by Lilly Research Laboratories. Prozac was the first of the class of drugs known as selective serotonin reuptake inhibitors (SSRIs)
that was approved for use in the United States. Prozac was first approved in
Belgium in 1986, one year earlier than its FDA approval date.
Prozac has been used by over 40 million patients across the globe. Prozac is approved for the treatment of depression in over 90 countries. Since its first approval, the FDA has now approved Prozac for the treatment of obsessive compulsive disorder and bullimia.
What is Prozac?
Prozac is a prescription medication. The active ingredient in Prozac is
Fluoxetine. The fluoxetine in Prozac helps to restore the balance of brain chemicals by increasing the amount of the neurotransmitter serotonin.
Prozac and other SSRIs do not cure depression or anxiety disorders. Instead,
Prozac helps to relieve the symptoms of depression and anxiety that plague so many Americans. Prozac has helped millions of patients live happy, vibrant lives.
Taking Prozac
Prozac is taken orally, usually once a day. Prozac is typically taken in the morning. Take Prozac with or without food, only as directed. Only take the exact dose of Prozac as prescribed. Do not take more Prozac than described, and do not stop taking Prozac without first talking to your doctor. Prozac may take several weeks to become effective.
Prozac Side Effects
Prozac may cause side effects for some patients. Common side effects from
Prozac include; trouble sleeping, headache, nausea, dry mouth, drowsiness, sweating, or stomach upset. These side effects from Prozac typically disappear as treatment progresses. If these side effects from Prozac use worsen or become bothersome, talk to a doctor. Serious side effects from Prozac use may occur.
These should be reviewed by a doctor immediately. Serious Prozac side effects include; decreased interest in sexual activity, flu-like symptoms, including chills, fever, weakness or muscle aches, loss of appetite, unusual weight loss, unusual or severe mental or mood changes, uncontrolled movements (tremors), changes in vision, problems swallowing, swelling or white spots on the tongue or mouth, changes in sexual ability, or painful/prolonged erection. The following side effects from Prozac are very serious. Seek medical attention immediately if you experience fainting, or irregular or increased heartbeat. If symptoms from allergic reaction to Prozac develop, such as itching, rash, swelling, difficulty breathing or dizziness, seek medical attention at once.
Any other side effects caused by Prozac should be reviewed with a doctor.
Precautions with Prozac Use
Discuss your complete medical history with a doctor before using Prozac. Tell your doctor if you have kidney problems, liver problems, allergies, heart problems, a history of seizures, or diabetes before taking Prozac. Prozac may cause drowsiness or dizziness. Do not drive or operate machinery until you know how Prozac reacts to your body. Alcohol intake should be limited or avoided altogether while using Prozac. Prozac may heighten the effects of alcohol.
Prozac should not be used by patients with a history of alcohol or drug problems unless advised by a doctor. Elderly patients may be more sensitive to the effects of Prozac. Discuss Prozac use during pregnancy with a doctor.
Generally, Prozac is not advised for use in either pregnancy patients or patients who are breast feeding. Prozac is excreted in breast milk. If a Prozac overdose is suspected, contact the hospital immediately.
Prozac Dosage
Only take the precise dosage of Prozac that has been prescribed. Taking extra doses of Prozac will not help symptoms, but can increase side effects. Do not double up doses of Prozac. If a dose of Prozac is missed, take it as soon as possible if it is not close to the time of the next dose. Otherwise, skip the missed Prozac dose and continue on with the normal Prozac dosing schedule.
Prozac and Other Drugs
Prozac used in combination with certain other drugs can be very dangerous, and even fatal. Discuss all medications that are currently used or that have been used recently with a doctor before starting on Prozac. Do not take the following medications at the same time as Prozac; MAO inhibitors, including isocarboxazid, linezolid, procarbazine, furazolidone, moclobemide, phenelzine, selegiline, or tranylcypromine (within 2 weeks), thioridazine (within 5 weeks), weight loss medicines, such as phentermine or sibutramine, astemizole, thioridazine, or terfenadine. Before using Prozac, tell your doctor if you take the following; sleep medications, propafenone, tranquilizers, haloperidol, other SSRI antidepressants, nefazodone, trazodone, venlafaxine, migraine medications, tramadol, tricyclic antidepressants, flecainide, clozapine, lithium, tryptophan, muscle relaxants, psychiatric medicine, blood thinners, anti-seizure drugs, herbal medicines, anti-anxiety drugs, narcotic pain relievers, or antihistamines. All medications and over the counter products that may cause drowsiness should be reviewed by a doctor before being taken at the same time as Prozac. Tell your doctor if you take drugs that affect heart rhythm before taking Prozac. Do not start using a new medication at the same time as Prozac without first telling your doctor. Prozac can affect blood sugar levels. Discuss all anti diabetes medications with a doctor before using
Prozac.
Storing Prozac
Prozac should be stored safely out of the reach of children or pets. Keep
Prozac at room temperature. Don't store Prozac in the bathroom or near heat or light sources. Never share Prozac with another person."

Wow! Isn't it just like those drug companies to come up with one drug that will throw our body back into menopause with hot flashes and make it not work well with the "antidepressants" we will need to survive the side effects of the drug!

So like I see it.....we either have a choice of letting the cancer destroy our lives or living a few years longer in misery and depression with Tamoxifen. "Quality" of life has got to have some meaning even for bc patients.

Maybe the drug companies now need to find an antidepressant which WILL work with Tamoxifen! If anyone hears of any, please let me know it's name. Thanks!

Your statement was, "As I experience it now in the US and the medical profession, they" seem to take that power away from me by trying to impose drugs on my body which I may not be able to withstand." I guess I am doing well. My oncologist here in the USA suggested I take Tamoxifen and she gave me all her reasons. I told her I was choosing not to take it. She was not forceful, and ask me at the next few visits if I had changed my mind. I continued to tell her no, that for me, I did not feel it was an option. She respected my right to make that decision for myself. I do not feel my decision is for everyone, this is strictly a personal choice.

I do want to state that I feel my doctor was doing her job by making her suggestion and giving me her reasons for her decision

Betty.

I will be starting Tamoxifen hopefully this week so I did some checking on this interaction between certain antidepressants and Tamoxifen. From what I found, it is the SSRIs which are the problem. It seems Prozac,
Zoloft, Paxil and a host of the newer drugs are SSRIs. I was checking mainly about Elavil and it was not listed as an SSRI on the site I was reading. So I take it, it is safe to use Elavil with Tamoxifen. Does anyone know if the newer drug Remeron is in the SSRI category?
I also think the interaction has a lot to do with the quantity one takes of these SSRIs but I could be wrong.

I will, of course, double check with my pharmacist to make sure Elavil and/or Remeron are ok to take with Tamoxifen but if anyone has info, please let me know what you found. Thanks!

Yes, sorry, my mistake - see my post in another branch of this thread.

Technically, it doesn't. However, more recent research indicates that
Tamoxifen doesn't seem to work as well in those who are both ER+ and Her2+ In fact Tamoxifen has a failure rate of about 35 to 30% in those who are ER+
Before I started hormonal treatment my husband questioned whether the failure rate might be related to being both ER+ and Her2+. He presented that hypothesis to my oncologist who thought that was an interesting possibility.
Shortly after research came out suggesting that appeared to be the case.
That connection was what made me reluctant to take Tamoxifen. I learned that the only way I could get an aromatase inhibitor at the time was by rejecting
Tamoxifen. However, there is another possibility that I didn't mention--and that is that Herceptin might allow Tamoxifen to work in those who are Her2+
That is an interesting possibility and for awhile did think about trying it since I was on the Herceptin.
Also, a small study came out a little over 2 years ago. I can't recall how many subjects were in it but results indicated that Femara worked much better than Tamoxifen in those who were Her2+ I showed that study to my oncologist but he did not feel it was a large enough study to draw definate conclusions.
I talked with the head researcher about the study and my case. He thought that an aromatase inhibitor might be better for me. This researcher, also an oncologist, still prescribed Tamoxifen, too. My aunt also talked with her oncologist--head of hematology/oncology at NYU hospital and he concluded the same.
I have also read of some studies that showed that aromatase inhibitors may also be less effective in those who are Her2+ In fact I have read mixed results re such.

it's misery but man must be allowed to be tied to tubes so he can stay
"alive". >>

I had similar thoughts during my mother's last year of battle with breast cancer. My thoughts were that we treat animals more humanely than humans.
There came a time when she was no longer the woman who was my mother. She had raging thoughts that were senseless and beyond her control. I am not sure how much she even understood about the world and what was happening around her...

Bea wrote << "Quality" of life has got to have some meaning even for bc patients. >>

AND that is different for each one of us and should be left up to the interpretation of each individual, if they are capable of making that determination. I would hate for that to be put on a rating scale and for some
3rd party to arbitrarily decide such based on a survey from input of others.
For some the idea of being without breasts is worse than the experience of hot flashes or even physical pain; for others there may be other quality of life factors involved. Some families want their loved one around in order for future generations to have the experience of at the least getting to know them;
others want their memories of themselves only to be that--and at a time when they did not have cancer. Still, others (and other cultures) don't concern themselves with those issues and see a the failing health of a family member as a natural course of life and take care of them to the best of their ability until they are no longer with us. It's kind of the same with disabilities.
One parent I know moved to the U.S. from China because her disabled son's life was in danger. We were told that it is not uncommon for disabled children to be killed at birth. She left/divorced her former husband for the sake of this child.
Who determines 'quality of life' or who should be allowed to make those decisions...just some food for thought...

By the book, the estrogen deprivation side effects should reduce over time, so the sentence isn't quite so bad as it first appears. Now I know that the side effects vary a lot between patients and I know that some don't get much problem and some get chronic problems. The implication however is that any anti-depressants used may not be needed long term, and so any antagonism for the Tamoxifen will be limited.

Anyway as you say there is a risk-quality balance to be struck and perhaps the relatively small increase in risk is justified by the improvement in life quality. There are no absolutes here and this one is particularly personal.

patient (in this case, myself) should have the right to decide what they consider their quality of life should be. >>

I agree with that completely. My question re such was hypothetical.

Well then we should make sure that WebMD site corrects it's info:

"Amitriptyline is in a class of drugs called tricyclic antidepressants.
Amitriptyline affects chemicals in the brain that may become unbalanced and cause depression."

I also found numerous other sites which list it as a tricyclic and all my life that is what I was told it was and that is how it is listed in my own personal PDR. If they have recently reclassified it, then WebMD and the PDR should be corrected, IMO. It can be very important that people know and understand how their drugs are classified when taking with a slew of other drugs.

On a lighter note, I think the moral of antidepressants is "the people at the

Yes I did post the aforementioned post. With Webtv, we can smallify with our own "thingees" so we don't have to be concerned with what will

Herp2+ and ER+. So.....it's Arimidex for me soon as I complete my radiation treatments..

I was sure glad to read that Kaye said she is on it and isn't having tremendous problems so far. I will "try" to keep a positive atitude about it and maybe I can do well on it too. Thanks for sharing that info Kaye!