The People's Perspective on Medicine

FDA Warns of Serotonin Syndrome

Serotonin syndrome can be life threatening but many health professionals are unaware of the drug combinations that can trigger it. Beware drug interactions!

Several years ago we got a desperate phone call from a friend. He was afraid his wife had suffered a stroke.

She was in a coma, unresponsive and he feared he would soon be forced to decide whether to discontinue life support.

A CT scan, however, revealed no signs of stroke. The neurologists were puzzled. They began to suspect an infection in the brain, but cultures came back negative.

After four days she began to return to consciousness and gradually recovered full brain function. The doctors were mystified.

The Mystery Resolved:

Our friend began doing some research and asked us whether the rizatriptan (Maxalt) his wife took for a migraine headache might have interacted with the sertraline (Zoloft) she was taking to prevent migraines.

Bingo! Both medications can raise serotonin levels and together they can cause serotonin syndrome.

This woman had experienced all the symptoms of this potentially deadly condition. Although her experience was reported to the FDA, the agency did not express much interest. For the most part, doctors do not recognize serotonin syndrome. As a consequence many times they are mystified. It is infrequently diagnosed or is misdiagnosed as something else, like a stroke.

The FDA Responds:

At last, though, the FDA has issued a Public Health Advisory to warn physicians of the hazards of mixing migraine medicines such as almotriptan (Axert), naratriptan (Amerge, Naramig), frovatriptan (Frova), sumatriptan (Imitrex), rizatriptan (Maxalt), eletriptan (Relpax) and zolmitriptan (Zomig) with many popular antidepressants.

Drugs like citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), fluoxetine (Prozac) and sertraline (Zoloft), or related medications such as duloxetine (Cymbalta) and venlafaxine (Effexor) fight depression in part by changing levels of the brain chemical serotonin. Combining them with other medicines that affect serotonin, including the triptan migraine drugs above, could be dangerous.

Other drugs that may interact badly with these antidepressants include prescription pain relievers such as meperidine (Demerol) or tramadol (Ultram), the nonprescription cough medicine dextromethorphan (Robitussin DM, among others) and some herbal products containing St. John’s wort.

OTC Drugs and Serotonin Syndrome:

Some people may experience serotonin syndrome as a result of interaction with an OTC drug. Several years ago, we heard from a teacher who was taking Paxil. When he caught the flu, he took a nighttime cold medicine so he could get some sleep. Instead, by the middle of the night he was extremely agitated, dizzy and shaking. When he began throwing up, his wife took him to the emergency room, where he was diagnosed with serotonin syndrome.

As the FDA cautions, people taking two prescribed medicines that may interact should talk with their doctors before discontinuing either drug. But it makes sense to be aware of the danger.

Symptoms of Serotonin Syndrome:

Symptoms of excess serotonin include anxiety, restlessness, rapid heart beat, sweating, nausea, vomiting, diarrhea, uncontrollable tremors or muscle contractions, lack of coordination, confusion, high blood pressure, hallucinations or coma. The syndrome may be mild, with dizziness, nausea and sweating, or it may be severe, landing someone in the hospital in a coma, or even killing him.

Another Story from a Reader:

Charlotte in Plano, Texas shared this nightmare:

“My husband took tramadol after a lithotripsy procedure to break up a kidney stone. He was also on sertraline.

“After just one dose he became very agitated. He experienced extreme paranoia and terrifying hallucinations. After calling the doctor I took him to the emergency room. It took both my son and me, along with a tech, to prevent him from ripping out tubes and leaving.

“It took three injections of Valium and some other sedative to calm him down and put him out. His eyes never closed.

“We finally brought him home where the nightmare began of his getting out of bed and falling numerous times. I was told that he was allergic to the tramadol. Neither the prescribing physician nor the hospital staff connected the dots regarding an interaction between the sertraline and tramadol.”

We are grateful that our friend’s wife survived her terrible experience with serotonin syndrome. We are glad the FDA has finally warned the American public and their doctors about this potentially deadly drug interaction. We fear that too few people realize this kind of drug interaction can be dangerous, if not deadly.

Revised: 3/1/17

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About the Author
Terry Graedon, PhD, is a medical anthropologist and co-host of The People’s Pharmacy radio show, co-author of The People’s Pharmacy syndicated newspaper columns and numerous books, and co-founder of The People’s Pharmacy website. Terry taught in the Duke University School of Nursing and was an adjunct assistant professor in the Department of Anthropology. She is a Fellow of the Society of Applied Anthropology. Terry is one of the country's leading authorities on the science behind folk remedies. .
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I’ve been on Tramadol, Oxycodone, Hydrocodone, Percocet, Dilaudid, Morphine, and Fentanyl over the past 16 years (doctors keep changing me around). The worst withdrawal was with Oxycodone. Something that causes such a terrible withdrawal experience certainly should be kept for ‘end of life’ treatment if possible.

I experienced little difficulty when taken off Hydrocodone, Percocet, Dilaudid, Morphine, and Fentanyl, and in all cases Tramadol was the replacement pain reliever and continues to be so. When I’ve run out I’ve had nothing but the increased pain that I take Tramadol for but NOTHING else happens to me in the way of any withdrawal symptoms nor do I suffer from any side effects.

My doctor said to NOT take Tramadol with any other drug, and my other medications must WAIT for 3 to 4 hours before I can take them, so I have a printed schedule for when I can take my medications. Therefore, there’s no adverse interaction.

I’m quite suspicious that people are taking multiple medications AT THE SAME TIME, and that’s where that ‘cocktail’ causes so many of these side effects (according to my doctor).

I’d recommend each person do the same as I’m doing – space out your intake of your medications; make sure you are taking as directed, and if it says to take with food DO SO because I’ve only suffered problems when I’ve forgotten to take with food. Some drugs say to take with or without food so that’s an easy solution.

I’m also hypothyroid. I take my supplement at 4 in the morning ON AN EMPTY STOMACH (the only way a thyroid supplement will work properly and I DO NOT DRINK GRAPEFRUIT OR ORANGE JUICE when you take it because it will negate the effects). Then I set my alarm for 8 AM – take my Tramadol; set the alarm for noon when I can then take my heart medication with my blood pressure medication together. Then at 4 PM I take my second dose of Tramadol and wait until 8 PM to take my Xanax and the rest of my heart medication. I take all medications with just water and 8 ounces of water each time (another key factor – don’t use milk; juice or cut short the 8 ounce minimum amount). The last pain pill of the day is midnight and I sleep just fine (in fact my sleep has improved since I’ve set up this schedule for myself).

I no longer take OTC medications because they interact adversely with prescription medications, so the only thing I do take is the low-dose aspirin because I’ve had two heart attacks and quadruple bypass and I’m trying to avoid another heart attack.

I’m never pain-free but I have pain reduction enough so I can muster through the day. I find getting 10 hours of sleep a day is what helps me deal with it. Refreshing my body in this way allows me to better manage my mental outlook. Keeping a strict schedule for my medication intake by setting my alarm clock so I don’t miss the optimum time to take it is what helps me as well.

I have been taking tramadol for a week. Am experiencing odd symptoms. Was unable to sleep and last night, and if I dozed off I had a horrible nightmare. Thank you for this information. I have not had medication since 10 last night. Hope this goes well.

I was prescribed Tramadol (had never taken before) after foot surgery. I took for two weeks and began tapering off of it. I had severe motion sickness feeling for three weeks while stopping tramadol. I took dramamine for relief. I developed vertigo which was only when I lay down and moved my head- but in reality the odd daytime symptoms I had were part of vertigo. I didnt feel clearheaded-just an off feeling with slight underlying nausea. I had head sweating attacks followed by being cold. I fell during major vertigo episode when i was reaching for shoe on floor with subsequent hip fracture. I have taken Effexor a long time and discovered possible interaction with Ultram.

I was started on tramadol about 2 months ago for shoulder pain. They worked for pain then about a 2 weeks ago started noticing that my muscles were getting stiff and rigid, soreness in legs and arms. Itching is severe. I started looking to see what was going on. Tramodol is only new medication that I have taken so that is what I started checking.

Now I know that’s my problem. My doc is not working today so I can’t notify him, but I’m not going to take anymore. How long will itching and sore rigid muscles last. Wish I had known this to start with, would never have taken them.

I just spoke with my son about tramadol (he was using them too), and he swears by kratom. He said once he used it, he never took another tramadol, had no w/drawal from the trams and has never even thought about trams again. He was taking 150mg twice daily. If he can do that, I can stop my 100-mg two-three times daily use. I wonder if it makes a difference that I’ve been on it 22 years and he was “only” on it for three.

I’ve have been taking Tramadol for about 14 years now. It amazes me that none of my Dr.s had spoke about taking me off of them. I have my problems with pain. And always will I assume. I was reading the side effects of Tramadol last week and decided to stop taking them. And because I assumed that it probably wasn’t helping me anymore anyways because of the length of years that I’ve taken them. Here on day 7 of not taking any Tramadol. I dressedecided to look at sideffects of stopping them cold turky. I have experienced the shock feeling. Flushing, shivering, feeling of a fever but not having one, dizziness. I wasn’t putting all of this together In till I saw other peoples testmonyies. I’m going to go see my Dr. And let him know I stopped taking them. I’m glad this site is here. And thankful for people sharing their experiences. It helped me to understand. And I hope it helps others. Thank you..

I forgot to say I’ve taken two 50 mgs a day. The script said two every 4/6 hours. But I kept myself at two a day all these years.

We are literally being forced to consider buying illegal drugs on the street–and even having to become dealers just to afford them. Isn’t that proof positive that the medical profession is mentally ill?

I was prescribed tramadol for pain on Wednesday I took the right dosage. Today I felt like I had no coordination. My vision was blurry. I was very slow 1 minute the fast the next.. I couldn’t hold a conversation. I was confused.. It was the worse experience of my life..

I have been told to get off tramadol for a week before have oral surgery because it may contribute to excess bleeding. I’ve never been told that before and I was taking tramadol at the time.

The said 7 days I’m giving it 4. I did cold turkey off of it once before when I was going to be given an opioid for a broken foot. After about 5 days I would have terrible laughing and crying jags. But I still have not read anything about the possibility that it can increase bleeding. I’d like some help with that. Thanks in advance.

I have been taking tramadol for 17 years for extreme back pain. Last spring, and again this past November, I had undergone spinal surgeries to alleviate these problems.

At first, I was on oxy but after 1 month or so I went back to tramadol, my PCP has left town and I haven’t gotten a new one. I just ran out of tramadol and am feeling lousy. How should I proceed?

Dear ones, I was reading my regular email and suddenly had the impulse to get on my knees to pray. I was given tramadol in an emergency room situation and was not told anything to do later. I refilled the prescription and asked the pharmacy if it was addictive. he said no. When I saw my dr. , told him I was taking 50mg tramadol once a day, told him the pharmacy said it was not addictive, he said “he does not know what he is talking about”

I was unaware the change in my personality or other issues of not wanting to be with people, thinking all the time about me, depressed and unsocialble. My personality has changed from being a loving person, joyful to this and only on 1 50mg a day. When it wears off pain gets bad again. What I am trying to say is that when I got back to the computer there was all this stuff about tramadol and I feel God immediately answered my prayer.

Thank you is not sufficient to y thank you for being there for us. Years past I found low thyroid through your news column, followed your advice and have been on levoxyl for years. I intend to start in the morning tapering off and hope for the best.

I, too, experienced a mild bout with seratonin syndrome. I took 5-htp along with melatonin before bed. I became anxious, then had chills and trembling just like I would get with a fever, except I didn’t have a fever. After about an hour, they went away.

After this article I plan to make sure my local pharmacy is aware of this FDA warning. I’ve printed out the article for them. I wonder how long it takes for local pharmacies or other pharmacies to catch up with updates like this. Thank you, People’s Pharmacy!

I have been taking 5hTp as an antidepressant for many years. It is over the counter. I wonder if it interacts with other drugs as well and if there is a risk of Serotonin syndrome with it?

I have been taking the max doses of Tramadol, Valium and Percocet for 18 years. My doctor said that the DEA is taking everybody off of these medications. I’ve been weaning off everything for 6 weeks and feel like Hell! I don’t know if my doctor is going to stop the weaning off and give me Soboxon, but you need to be off the medication for 48 hours, and I don’t know how I’m going to do it. I see my doctor on Nov. 23. I hope he continues to wean me off. For the last 6 weeks I have felt like I’m going to die! Is there anyone out there who can give me some advice. My pain and anxiety started from carbon monoxide poisoning.

I was given tramodol 50mg x2 : to be taken 3 times a day following my 2nd operation for a shoulder injury, I went from being a quite physical person previously, to a fragile felt like dying person within weeks of taking the drug.

It helped so much with the pain I could do things with my arm I hadn’t done for a long time, so I didn’t question tramodol? I made sure I got my repeats in time I had my life back, no pain, I suffered from insomnia for years and have been on zimovane for years, I noticed my sleep started to stop which causes me anxiety, so I started to cut my tramodol down to 1x 3times a day, still not sleeping, I started noticing hallinuninations which I just scrubbed away, starting vomiting till I couldn’t take as much as a sip of water so any meds in me, were quickly coming out of me, I couldn’t walk felt like I was going to faint, I had jitters, just felt like I was going to die, even discussed my funeral /hospital things,

I lost over a stone in weight in a week, eaten nothing in a week, slept none in a week, finally with everything out of me,I tried taking just 1 sleeping tablet, to be woken after an hour to the sick feeling again, with no hope I just gave up, was in bed with my bowl, aching ribs, shoulder pain worse, just wanted to die, totally exhausted.

My partner wanted to take me to hospital but as we had discussed my wishes he knew I didn’t want that, I started to self meditate, got myself up into shower, suddenly felt a little better, still dizzy, I just got my head around it, now totally tramodol free, I took my first sleeping tablet again and slept for 10 hours through , I am writing this the next morning feeling a little more human again , I feel that there should be a little less tramodol given out so easily and should come with a health warning about this drug,, never again will I take another that was a dreadful experience .

I have taken Tramadol for several years because of chronic back pain and other related problems, and I recently came down with bad flu-like symptoms (moderate to bad headache; muscle aches; severe heartburn; projectile vomiting). I had to stop eating and drinking completely for two days and my stomach and abdomen were so sore I stopped taking my regular medications, including the Tramadol, and I also stopped taking the few vitamin supplements I use.
Along with the flu symptoms, which were awful enough, I experienced restless leg muscle-jerks, shooting pains in my feet, episodes of chilling, several moderate anxiety attacks, pronounced insomnia the second night, and even a few minutes here and there of suicidal thoughts.

I’ve had a handful of dreadful drug-interaction problems in the past, along with several instances where I had allergic reactions to prescribed medications, so, despite the sudden severity of the additional symptoms while I was in the grip of the flu, I was pretty sure I was having some kind of drug withdrawal reaction.
I “talked myself down” from the worst withdrawal anxiety and emotional aggravation after the nastiest flu symptoms slowed down and I was able to work a very short shift yesterday.

Because of having several intestinal disorders, not all the flu problems have disappeared yet, and my insomnia is still strong.
I will let my regular doctor know what happened to me and that I think I had moderate to severe withdrawal symptoms from stopping the Tramadol for only two days (!!).

Unfortunately, using it does greatly reduce the sometimes excruciating back pain, so I don’t think I can stop taking it altogether.
I’ve read about other painkilling drugs, and I don’t even want to think about having to adjust to a new one: As the saying goes, “Better the Devil you know, than the Devil you don’t.”

I’m grateful I found this site!
I wish everyone struggling with use of the Tramadol the best possible luck in being able to cope with what can definitely be a very uncomfortable and traumatizing experience with side-effects.
Thanks again for being here so we can share information and gain insight and inspiration from each other!

I have been on tramadol for about a year, my kidney Dr. Said I had stage 3 kidney failure probably from taking to much advil. When I called in for a new prescription
They said that he would not fill that perscription for me any longer, he didn’t discuss tapering off or what I should do except tell my regular doctor to write the script, I don’t have a PCP, my last one just left town, I have been going through a living Hell, unable to sleep, feeling very whole body is shaking . I drank a 1/2 a bottle of Jack Daniels and was only able to get 3 hrs sleep. Should be a law against a Dr. Doing this to a patient

Hi all. I’m Yvonne I’m from the UK. I suffer from fibromyalgia and am in constant pain daily which I manage however I get flare ups where I’m in really bad pin from head to foot. I am prescribed Tramadol as I can’t take ibruprohen it effects my stomach codeine based meds make me sick.
Anyway my last big fkare up was just after xmas so took the tramadol they helped loads bit when I stared to feel better so I stopped taking them and am suffering from awful withdrawal

I live in the UK, so many of the brand names listed are un-familiar to me. Firstly, I am virtually off Tramadol for the 9th time (100mg’s x 3 times per day). The first 8 times were to try different drugs for a servere reflux stomach, that may have also helped with a neurological condition affecting my legs, spastic paraparesis, such as amitriptyline or baclofen – old drugs. With no results apparent, I returned to the Tramadol.

I had none of the night-mare tales described here, just one recurring effect in a form of dizziness which gradually decreased as I titrated downwards. Now to the 9th time, which is now. I have reduced from 100mg x 4 times per day down to 50mg, or an occasional 100mg in 24 hours and expect not to be taking any within 5-7 days. Apart from my obligatory hard to intermittent pulsing in my head, the only thing I am left with, and it is very unpleasant especially at night is itchiness, tingling & “burning spikes” all over my body.

Frankly Tramadol is not the ogre it is described to be and is even sold over the counter in some European countries in preference to codeine products. Just to cheer you up I have incurable, untreatable cancer known as NETs (al la Steve Jobs) which in my case the excess seretonin that formed a tiny nodule in my small colon has wrecked my liver (his went to the pancreas) and my bones and I am forced to take a nightly pre-migraine drug, Topiramate (really for epilepsy) and if it hasn’t worked I am then forced to take a Sumitriptan tablet as the headache develops. From what I have read here these type of drugs could be a dangerous cocktail with any choice of anti-depressant or narcotic as my cancer pain inevitably develops.

Any magic thoughts, I would appreciate. As for Tramadol, there is a trade off with every drug taken and you will be a long time waiting for the US to ban it. Xanax, the 4th most abused drug in the US is a banned substance in the UK because of addiction and Valium, while still licenced here, is only prescribed as a single 30 day script (usually the 2mg strength), or to the terminally ill. The scripts for Tramadol grow & grow, but morphine derivatives like oxycodone are only for the terminally ill.

I thought coming off Morphine was bad enough! I refused to take the tramadol at first because a pharmacist (friend) said she wouldn’t give it to her dog! I had major back surgery 6 weeks ago. When you are in so much pain I decided to take the Tramadol(100mg) 3 to 4 times daily, ooh, I felt so ill, so I just continued with the Morphine which I reduced so I tried 200mg slow realease tramadol which I could cope with but when it was time to reduce my dose, it was a different story!! The lethargy, sleepless nights, low mood, poor appetite, fuzzy head and generally feeling under the weather. I then reduced from 100mg SR to 50mg (when needed) it was still awful because it was not released slowly, I felt sick as a dog!
I have completely stopped as of today and will play it by ear and will try resting, falsing myself to eat toast, drink plenty of fluids and hope for the best!
This is an awful drug which robs you of your personality and your life but what do you do when you’re in soo much pain??
I WOULD definitely consult the chronic pain team and a Pharmacist for advice on juggling your medications as we are all individuals when it comes to pain/medication tolerance. Gabapentin has helped a great deal, so I will stick with it until I hope to become toxic free in the future!!!
I wish anyone with chronic pain, a pain free and medication free future.

Don’t want to impinge on your time with my “pain story”, suffice it to say that over 50 years of chronic back pain, starting with a shot down helicopter in Viet Nam, and having had several re-injury episodes over the years and continually getting worse as time has passed drove me into the arms of Tramadol about a year ago (550mg then 400mg then 250 mg to 100mg presently) the withdrawal effects have been EXACTLY and More intense than stated here!

I am being treated for PTSD and BiPolar with Lamotragine, Sertraline, Quetiapine and Gabapentin. So the psychological effects of withdrawal started as soon as I began reducing the dosage and today seem to be greatly exacerbated. Have an appointment with my MD and hopefully the VA psychiatrist and can get a handle on this mess!

I am VERY empathetic toward my “fellow sufferers”. Maybe we can share experiences and successes toward a resolution of this horrible state we find ourselves in. I Pray that we can be helped toward that resolution. Maybe we can find a way to support each other?

Gabapentin is the biggest scam of all. It does NOTHING–ZEEERO–for even the slightest pain. If it “works” for you, you are experiencing the “placebo” effect doctors hope you will. It DOES, however, seem to help short-term memory in some.

Thank you for your comments. I think would be excellent to support each other with this! I have severe arthritis and Tramadol was a miracle for me, giving me my life back…and non-addicting!! Ha!!! How could they be allowed to say that when they have no long term studies with proof? Well, no problem until I could not get a repeat prescription on time…pharmacy requested on Thursday…went through Friday to Monday, begging doctor’s nurse for the repeat. Was angry because the side effects were awful. I am still on the same 300mg ER, as rheumatologist discussed it at length with me, and the alternative would be opioids. Have decided to at least reduce drastically with medical help as we get into the new year. Meanwhile I will not run out! Take care of yourself! Seems it’s the only way!

Stephen, your story isn’t a bother at all, it’s been very enlightening.

First, thank you for your service. It feels like Vietnam vets are the new WWII vets, replaced by the ME vets who are getting more media attention. ALL vets should be appreciated more, so thank you.

Second, your story is somewhat similar to mine although the psych meds are old and the Tramadol is new. I’ve felt ‘fluish’ since quitting it about two weeks ago but it’s gotten pretty bad today–not very common for flu which comes in like a hurricane and trails off with time. I was only taking the Tramadol for about a month and a half but am extremely sensitive to side effects so it isn’t surprising that I feel this bad I guess.

The more I read about Tramadol withdrawal and serotonin syndrome the more I think that’s what’s going on. I’ll see what I can do medically but my doctor’s appointment is a week away.

For support, Reddit can be a strange place but it can be a good place to start to look for support groups.

Take care, everyone.

I took a bad construction fall resulting in herniated, bulging discs, and lots of arthritis in lower back. I am taking zoloft and was prescribed tramadol, 100 mg (3X daily) as needed. I thought the pain was decreasing a bit, so stopped the tramadol and just took ibuprofen. That first nights sleep was restless, jittery, involved with involuntary muscle twitching (full arms and legs), and horrific nightmares. It was last night, that is why I am online trying to find answers.

My husband was taking oxycodone after his back surgery but the Dr lowered his dose to tramadol like you said in your article it’s not supposed to have the withdrawal symptoms but it does anyways lately he’s been sleeping very late (around 2am) wakes up feeling sad and also says he gets what you described as brain shocks but he recognizes them as thunder like sounds that only he hears.. I’m desperate to find something that he can do to stop taking pain meds and start working in a different method to help him cope with pain. Any advice??

This comment is for you as well as everybody else commenting here. Research Kratom and if you like it, join the effort to keep it legal. I think it is a miracle cure for many ills. It has saved my life.

I think this is happening to me. I take Zoloft, but couldn’t sleep so I took some Tramadol for about a month. Sweating, anxiety, irritable, muscle – flu like symptoms. I quit taking it a few days ago when I started investigating interactions between meds. So, no weening…just quit taking it.

This is very helpful information I was looking for answers and I was able to find them. Thank you

I thank God I found this Web site, I have been taking Tramadol for 5 years after a knee replacement. It took most of my pain away, I have suffered with leg pain and back pain for many years.
Lately I was experiencing restless legs when I went to bed, and I could not keep my balance, profuse sweating and shivers, also very bad stomach problems. I was diagnosed with Crohn’s disease then ulcerative colitis.
I felt like I was dying a slow death, I had a lot of anxiety and stress over all of this and was prescribed Xanax 25 mg. I looked up side effects of both tramadol and zanax there it was!!! I called my pharmacist the next morning and asked how to wean myself off of these poisons, he explained to me it had to be a very slow and gradual weaning. It has been 30 days since I started, and was feeling most of the withdrawal symptoms mentioned here. Although I have to say I have not been off balance, I feel like I am getting better.
I am writing this in hopes it will help others to understand how deadly these medications are.
It is almost 2 AM and my legs were jumping so badly I decided to give my input here. I have taken two 325mg of aspirin that seems to help. I will try and go back to bed now and hopefully get some sleep.
I will not go back to tramadol or any other narcotic.
My hope is that doctors will realize that most of these meds they prescribe are the cause of more illnesses.

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