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Antidepressant Reacts Badly With Cold Medicine: Interaction Can Be Deadly!

The antidepressant paroxetine plus dextromethorphan in a common cold medicine sent one reader to the hospital. Beware serotonin syndrome. It can kill!

When you reach for an over-the-counter medicine, do you think about whether it is compatible with other drugs you may be taking? Few people do, but that could be a big mistake. Even cold medicine could trigger a potentially lethal interaction. Have you ever heard of serotonin syndrome? It can be a killer!

Cold Medicine Plus Paxil Led to an Emergency Room Visit:

Q. I am a 38-year-old teacher at a private school. In the last several years the pressures of the job have increased considerably, and I have been feeling the stress.

A psychiatrist has prescribed a number of medications for mild depression. Fluoxetine (Prozac) upset my stomach and trazodone made me too drowsy to function. Now I am taking paroxetine (Paxil).

A few weeks ago I came down with the flu that was going around. I took a night-time cold medicine expecting it would help me sleep. But in the middle of the night I was too agitated to sit still. I felt dizzy and couldn’t stop shaking. Needless to say, I couldn’t sleep. When I became nauseated and started vomiting, my wife took me to the emergency room.

While waiting to be seen, I experienced tremors, diarrhea, confusion and had trouble breathing. The doctors said something about serotonin syndrome and gave me diazepam.

What is serotonin syndrome? Should I avoid cold medicine from now on?

What Is Serotonin Syndrome?

A. Serotonin syndrome can be extremely dangerous, if not lethal. People who are taking a medication that works through serotonin, such as the popular SSRI antidepressants paroxetine, fluoxetine and sertraline, may be susceptible to this condition if they are taking certain other medications. The antidepressants phenelzine (Nardil) or tranylcypromine (Parnate) are especially dangerous in combination with SSRI drugs.

Over-the-counter cold medicine containing the cough suppressant dextromethorphan (DM) can also interact with SSRI antidepressants (Skop et al, American Journal of Emergency Medicine, Nov. 1994). The drugs inhibit an enzyme (CYP 2D6) that is essential for metabolizing dextromethorphan (Ereshefsky et al, Clinical Pharmacokinetics, Suppl. 1, 1995). Paroxetine appears to affect this enzyme more strongly than most other SSRI antidepressants.

Because dextromethorphan is so common in cough and cold medicines(it’s the DM in Robitussin DM and dozens of other products), you need to be especially vigilant. For as long as you remain on this antidepressant, you should avoid cough or cold medicine with DM in the name or dextromethorphan in the ingredient list.

Other Drug Combinations Can Trigger Serotonin Syndrome!

Other medications can also predispose to serotonin syndrome in the wrong combination. Be cautious if you get a prescription for duloxetine (Cymbalta) or any other antidepressant. Tramadol could also lead to serotonin syndrome in combination with paroxetine (John and Koloth, The Australian and New Zealand Journal of Psychiatry, Feb. 2007). Fentanyl can also interact badly with paroxetine (Greenier, AANA Journal, Oct. 2014).

One medication that doctors might not connect to serotonin syndrome is the antibiotic linezolid (Zyvox). Nonetheless, linezolid could interact with the Parkinson drug carbidopa/levodopa to cause serotonin syndrome (Pettit et al, Journal of Clinical Pharmacy and Therapeutics, Feb. 2016). Another Parkinson drug, rasagiline (Azilect), also interacts with linezolid to trigger serotonin syndrome (Hisham et al, Indian Journal of Pharmacology, Jan-Feb. 2016).

Symptoms of Serotonin Syndrome:

Classic symptoms include agitation, confusion, hallucinations, rapid heart rate (palpitations and/or tachycardia), diarrhea, nausea or vomiting, fever, muscle spasms, overactive reflexes and rapid changes in blood pressure. There are, however, many other possible symptoms, including seizures and severe joint pain (Physical Therapy, June, 2008; Werneke et al, BMC Neurology, July 12, 2016). Doctors and pharmacists must be vigilant to prevent such drug interactions.

Readers’ Stories:

Although serotonin syndrome is considered rare, some other readers have experienced such an interaction. Here are a few stories to illustrate how dangerous this reaction can be. The first one involves gabapentin and tramadol along with duloxetine. Since gabapentin and tramadol aren’t antidepressants, the potential for this serious interaction might not be recognized immediately. Tramadol has been identified in numerous cases of serotonin syndrome, however, and this must be taken into account by patients and physicians (Beakley et al, Pain Physician, Jul-Aug. 2015).

A Serotonin Syndrome Story:

V.V. was taking once-a-day gabapentin (Gralise) and tramadol for pain, plus the antidepressant duloxetine (Cymbalta):

“I too had a very bad interaction from taking Gralise, tramadol and Cymbalta. The doctor told me that I had serotonin syndrome. I was weaned off twice and it has been 3 weeks since I have had any Cymbalta.

I believe that the FDA should be put to task for the lack of an appropriate weaning schedule and lack of appropriate box warnings.” 

Preventing an Interaction:

Some of our readers have realized that this interaction is far too risky to ignore. They have taken it upon themselves to monitor their prescriptions to make sure they or their loved ones do not take medicines that might trigger serotonin syndrome.

E.J. had to educate her doctors about two different interactions: Prozac plus the DM (dextromewthorphan) cough medicine and ibuprofen and antidepressants:

“Unfortunately, as stated above, many doctors do not seem to know about serotonin syndrome. My daughter takes fluoxetine (Prozac) and I actually had to tell two different doctors about serotonin syndrome when they wanted to prescribe her cough syrup with dextromethorphan in it.

“Also, ibuprofen can be a problem too for people who take antidepressants. I am glad I had read about it so I could tell the doctor. She went and looked it up and came back and said I was right and that she had learned something today! Amazing, but rather scary!” 

Ibuprofen and  and SSRI antidepressants can interact and cause serious digestive tract bleeding (Hersh et al, Clinical Therapeutics, Supplement, 2007). We suspect that most health professionals are unaware of the dangers of this drug interaction.

Millions of people take drugs like fluoxetine, paroxetine and sertraline for depression. Many of them also have aches and pains that may lead to the use of NSAIDs like ibuprofen (Advil, etc) or naproxen (Aleve, etc).

As far as we can tell, there is no specific warning about this drug interaction on the label of these OTC pain relievers. Many people do not heed the warning to ask a doctor “if you are taking any other drug.” 

Researchers writing in the American Journal of Gastroenterology, June, 2014 warn their colleagues that the risk of upper GI bleeding:

“…is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.”

Sudden Withdrawal Can Be Trying:

A person with serotonin syndrome may need to stop the medications immediately, as a matter of life and death. The aftermath of dealing with medication withdrawal can also be pretty terrifying.

L.D.V.D. describes what it is like to stop tramadol and duloxetine (Cymbalta) suddenly:

“I have been on tramadol for pain and Cymbalta for depression. I got depressed due to the constant pain I was in-sciatic nerve pain. About 10 days ago I felt extremely sick. Got myself out of bed and off to a doctor. She immediately said that I have serotonin syndrome and must go to hospital emergency department. She called them.

“They ran drips into me which stopped the uncontrolled twitching. They informed me to stop taking tramadol and Cymbalta immediately. Well, that was like sending me straight to hell! I have been so ill the last 10 days. Today is the first morning I could get out of bed without first walking into something.

“My symptoms are as follows:

“Severe brain zaps. If I move my eyes, I get brain zaps. Had really bad flu. Hyperthermia. Wake up every night and my pj’s are soaked through. My husband said he touched me one night as I was restless in my sleep. He said I was all wet. I have had diarrhoea now for 6 days. Get very weird dreams. In last 2 days I have felt depressed, crying my eyes out – the next minute I want to punch someone. Please tell me it will stop.” 

You can learn more about withdrawal from duloxetine or tramadol at these link:

How To Stop Duloxetine (Cymbalta) Without Withdrawal Symptoms

Tramadol Side Effects and Withdrawal are Daunting

Two people we know suffered from serotonin syndrome. One died, while the other recovered after a week in a coma. We describe these cases and other deadly drug interactions in our book, Top Screwups Doctors Make and How to Avoid Them. The chapter titled “Drug Interactions Can Be Deadly” provides our Top 11 Tips for Preventing Dangerous Drug Interactions. If you follow our guidelines you might be able to protect yourself or a loved one from serotonin syndrome or one of the other scary incompatibility reactions.

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Share your own drug interaction story in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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  • Anglin, R., et al, "Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis," American Journal of Gastroenterology, June, 2014, doi: 10.1038/ajg.2014.82
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