It is commonly recognized that certain medications should not be administered with some others. What is not well known is that several over the counter (OTC) medications and herbal supplements can be lethal if taken with SSRIs.
I have a patient who was taking fluoxetine and, experiencing some difficulty with sleep, decided to take one tab of melatonin. He woke up with a red and burning face, headache and blood pressure of 230/180. He was in a full serotonin syndrome.
Serotonin syndrome symptoms often begin within hours of taking a new medication that affects serotonin levels or excessively increasing the dose of one you are already taking. Symptoms may include: Confusion, agitation or restlessness, dilated pupils, headache, changes in blood pressure and/or temperature, nausea and/or vomiting, diarrhea, rapid heart rate, tremor, loss of muscle coordination or twitching muscles, shivering and goose bumps, heavy sweating.
This syndrome may develop within hours to days of increasing a serotonergic dose or adding a serotonergic agent to a drug regimen already containing a serotonergic medication. Symptoms range from mild and chronic, to others that progress quickly to death. My patient is lucky to be alive.
It is essential that persons taking medications that raise serotonin levels be warned that they must not add others that are often regarded as “natural” or “safe”. One of the most potentially dangerous is dextromethorphan (Benylin)
Since dextromethorphan is commonly recommended to treat a cough, the patient be advised of the risks associated with the use of dextromethorphan in combination with other serotonergic agents.
Who would think that rose hip syrup (a major source of vitamin C) can be just as dangerous? Or Gingko biloba?
The list of medications to be avoided in conjunctions with SSRIs and SNRIs is lengthy and includes the following:
Tricyclic antidepressants, MAOIs, amphetamines, lithium, bupropion, trazodone, all opiods including methadone, one antibiotic (linezolid), antiemetics including Gravol, dopamine agonists (Levadopa) and bromocriptine, triptans and many others that do not necessarily list serotonin as an ingredient.
In 1999, it was estimated that 85% of prescribers were unaware of serotonin syndrome.( Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-874.)
It is unfortunate that the responsibility often lies with the patient to determine whether or not an added medication is safe or not. In the case of melatonin, capsules it seems can also contain serotonin.
I am reminded of one of my favourite quotes from Sir William Osler:
“The person who takes medicine must recover twice, once from the disease and once from the medicine.”
Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-874.. Scary indeed.
US Pharm. 2010;35(4)(OTC Trends suppl):13-15.
Editorial Note: This post was by Dr Irene Campbell-Taylor. TaperMD is forthcoming from RxISK and will contain guides to medications that can trigger serotonin syndrome.
Another TIP-TOP article from Dr Irene Campbell-Taylor, a former Clinical Neuroscientist and Assistant Professor of Medicine at the University of Toronto.
Suffer The Little Children
August, 9, 2012 | 13 Comments
The prescription pad is the only thing doctors now have. As the little fellow in the film, asked why he is going to see Dr X, reply gleefully and accurately, “To get medicine!”
Another top-tip from Kristina
Kristina K. Gehrki
There isn’t one symptom listed here that Natalie didn’t exhibit. I wish it weren’t true. But it is. And many of these symptoms were shared w/ doctors.
TaperMD is a revolutionary solution to the problems of managing multiple medications in older adults. Developed with McMaster University, we built it to help patients, doctors, and pharmacists work as a team to address the serious problems of polypharmacy and drug side effects, and to fit in with normal consultation processes and flow. It is currently in clinical trials in Canada and Australia.
CBD oil interferes as a potent CYP2D6 inhibitor. Please be cautious.
This is a very important point and deserves a post by someone about their personal experience of combining cannabis and SSRIs. There is little question that SSRIs can cause a psychosis in some and if cannabis acts effectively to increase the dose of the SSRI being taken it would make sense that this can trigger psychosis in some
My eyebrows were raised when I saw the words “There is little question that SSRIs can cause a psychosis in some”.
I have suffered from Dysthymia for close to 18 years (provoked by a set of traumatic incidents during my mid and late teens), and had gone through 5 “double dip” depressions each a few years apart after that, often in winter, with very high anxiety comorbidity, for which I never sought any treatment (like many with dysthymia my perception of what a healthy emotional baseline is supposed to be was rather distorted so I didn’t recognize it for what it was, and felt ashamed, weak and incompetent).
Over a year ago I had a very bad “double dip” provoked by a very severe financial crisis which itself had followed 6 months of sustained high stress. My anxiety levels were through the roof for months, 4 hours of sleep every night for months, obsessive rumination and all that jazz.
This time I went to my GP and got referred to Health Minds (but with a huge waiting time), and prescribed the SSRI fluoxetine.
I had been on fluoxetine about 2 years before that, but only for a few months, for to some OCD symptoms that I had had for a few years that were interfering with my ability to work and study a part-time postgrad degree simultaneously. When my GP asked about depression I denied that I had it (I wasn’t lying, I genuinely didn’t realize that what I had previously experienced counted as such, because I never used to cry) I had no depression or anxiety at the time. My dosage was only 20mg daily and I reduced that to 10mg daily after 2 months and came off it. I had no side effects from that period at all, either on or coming off or afterwards, but my OCD symptoms vanished after a few weeks of starting the medication. Years later they hadn’t come back. So fluoxetine didn’t seem a bad idea this time around; same dosage as before, 20mg daily.
It is difficult to put into words the sheer suffering that I experienced.
My sleep went from 4 hours a night to 2 and a half hours, give or take 6 minutes (I am not exaggerating, I kept a record). That lasted for 36 days straight. But that was minor in the great scheme of things. My already obsessive rumination became even worse and I experienced a kind of emotional agony beyond and different to the ultra high anxiety and sense of emptiness and self-pity. It was a kind of what might be called “spiritual agony”.
The very fabric of reality seemed to take on a different character. Taking walks or visiting the shops took on a nightmarish quality, as animals and people ceased being living things and were now just machines moving around or were a booming random hostility. The textures and appearance of ordinary household objects signified death and decay in some abstract way. They were providing a kind of intuitive, forceful but abstract evidence that I was worthless and needed to die. However I didn’t hear voices in my head, like a schizophrenic might.
I know none of this makes any sense, its absolutely off the f*cking wall, but its the best I can do to describe the phenomenology of it without writing a 1000 word essay or some such. I don’t feel qualified to judge, but the above sounds like psychosis. Would that be a fair belief?
I also cried myself out endlessly, day after day. In all of my previous depressions, this sort of thing only happened during the original traumatic episodes when I was a teenager, not in any of the double dips since (I am in my mid-thirties). I never cried during those, even when things were very bad. I had never experienced suicidal ideation except in the original traumatic episodes. But after taking fluoxetine this time around I was thinking it very often. Only the thought that my family wouldn’t be able to afford my funeral (I come from a very poor background by UK standards), prevented me from doing so. I have multiple scientific degrees, and had read cognitive neuroscience as a hobby for years (though alas never about mental health, I was interested in things like theories of concept formation). That scientific knowledge did little to protect me from the delusions; my ability to think rationally was compromised. That’s how severe it was.
I went to my GP, told him that my anxiety was worse and my sleep pattern severely deteriorated, but I didn’t tell him about the suicidal ideation because I was afraid of being sectioned and being ruined entirely as a result. I also didn’t know how to express myself about the weird cognitions or that the emotional agony was different to anxiety, but did tell him about the constant crying.
He said that we should give it several more weeks, that everyone cries, that he didn’t need to know about my detailed history, because the cause of my current problem was obviously financial stress. Maybe change to a different SSRI or increase the dosage of fluoxetine in a few weeks. He also gave me some low dosage propranolol. I wasn’t encouraged that a possible side effect of the propranolol was less sleep. Needless to say this did next to nothing useful.
I came off the drugs at my own insistence and spent every lucid moment trying to understand what had happened better (I have studied medical statistics at postgrad level, which helps); watching the same videos by a certain Dr Healy, Andrew Solomon, Robert Sapolsky and a few others over and over again, trying to re-read Neuroscience books again and again, trying to put the pieces together.
[I have no proof, but one question that interests me is whether the SSRI provokes an increase in Substance-P in the dorsal raphae nucleus, which then affects the ventromedial prefrontal cortex. I wonder, because all of my episodes over the years have strongly involved very obsessive moralistic rumination, which screams of the ventromedial prefrontal cortex, which from what I understand is supposed to shut off the anxiety response when it thinks an anxiety inducing problem can be solved. Whereas the emotional agony, distinct from the anxiety sounds a lot like the work of substance-P, which is produced along with serotonin in the dorsal raphe nucleus, which also affects sleep pattern, and is linked the ventromedial prefrontal cortex]
I also got lucky and got offered out of the blue an easy summer job at a place I had worked at before, which stabilized my finances. However it took quite a while for my symptoms to dissipate after that good news (Over a week to lower to sort of bad depression with some anxiety thrown in for good measure and then a few more weeks to return to Dysthymia ) and I was emotionally scared for months afterwards.
I will never take SSRI’s again. I also wasn’t impressed by the very simplistic stuff I got over the telephone and in leaflets sent to me about anxiety. I teach myself CBT and other methods from advanced psychology books nowadays, and I find that a lot more helpful.
There’s need to be cautious about taking cannabis while having therapy sessions too. Letting thoughts flow amongst friends, streams of consciousness, philosophising, not following the unspoken ‘rules’ of the session can be be labelled as evidence of mental illness by a therapist
This is really interesting and vital to know. My son took Seroxat and having stopped it, soon afterwards took St John’s Wort, but didn’t tell anyone. He began feeling extremely unwell. The GP when he saw him at this time, ( he’d come home from Uni feeling ill) was very angry with us parents saying we should have known better than to let him do this, but he’d been away at Uni for many weeks, he was on Seroxat to help him cope with the low mood that RoAccutane isotretinoin (prescribed for his acne) had caused, he was 21, studying Biological Sciences, so presumably pretty savvy, and didn’t tell us anything. But from this article I now understand why the doctor got so angry. However it shows how young people do not know these dangers and would think St John’s Wort would be safe. It seems that taking it even after stopping Seroxat or 5HTP? Is very dangerous?
The dangers of mixing ‘so called’ natural alternatives with SSRI’s is underrated.
I can recall when I had very unbearable and unforgiving pain and pressure of the brain, a GP prescribed me Ginko Biloba.
This only made my matters worse.
I felt very dizzy and my morbid condition was amplified.
I agree with you Heather R , in regards to the dangers of mixing SSRI’s with other ‘so called’ healthy alternatives and other dubious concoctions.
There should also be a warning placed on these meds that undesirable/unwanted side effects or adverse reactions could result, as a result of mixing SSRI’s with other meds or ‘so called’ natural alternatives.
I must also mention that Health Professionals have NO CONCLUSIVE EVIDENCE of knowing the harm that results from mixing A/B/C or D.
This includes meds mixed with other meds.
Through clinical experience, surely, some senior Health Professionals, acknowledge what is occurring. It is NO SUPRISE!
They witness these negative results, every day.
To turn a blind eye and pretend that further health issues do not result, from mixing meds with meds or mixing meds with other alternatives, is indicative of a major problem within the medical system which needs to be addressed, so that patients cannot be put at further RXISK or HARM.
There should be NO EXCUSES for overlooking a patients medication history.
Health Professional do not manufacture the medication(s) and if one does not acknowledge the harms of mixing A/B/C or has no understanding of the dangers that are to come, one should try to avoid the perils of harm and err on the side of caution.
We must learn from PAST MISTAKES so that unnecessary HARM(s) can be eliminated and avoided.
If some Health Professionals choose LIFE, there should be NO EXCUSE(S) for RUINING or ENDING LIFE, unnecessarily.
Ralph Waldo Emerson once said that:
Life is short but there is always time for courtesy.
It’s a message that perhaps may well have been scripted for the modern healthcare professional.
It is about time, some Health professionals refrain from doing harm and attentively listen to how patients feel.
Positive changes can only take place when some Health Professionals stop building walls and create bridges to assist patients to heal from past mistakes.
It has amazed me for 20 years or more than no prescriber ever seems to query the possible dire synergistic effects of drugs, ie like Carla says, mix drug A and drug B and don’t worry about giving any thought to how they might work in a bad way together. We know that grapefruit should not be eaten whilst on certain drugs, and we know that Vitamin C in tablet form can double up the effect of others. We also know that taking Vitamin C can lessen intollerance reactions sometimes.
Now we know, from this excellent post, about the serontonin syndrome. I was last year inadvertently given in hospital a dose of 10 ml Oromorph (morphine) accidentally too soon (within 2 hours overlap) after two tablets of dissolved paracetamol. The nightmare visions of hallucinations which followed were indescribable. I did not dare close my eyes all night, and held onto snatches of reality with difficulty. This all because these medications had been given in good faith by the nurse, thinking they would bring pain relief.
The basic gist of my situation is that I was depressed and prescribed
SSRI Paxil by Toronto’s top Psychiatrist. I felt improvement. A Harvard educated DR friend’s example led me to try weed concurrently. I was psychotic for a year – my GP had no idea that anything was wrong despite my grandiose claims, like working directly for Michael Bloomberg. The change was imperceptible. I felt fantastic. But I then ended up in police custody then locked up for 2 months in a psychiatric hospital. When I was released I was treated by local docs/psychiatrists who had no idea what was wrong with me – they thought it was “just” bipolar. Cannabis psychosis will become more common now the weed is legal here. I just want the general understanding of this to be elevated, especially amongst medical practitioners. I think of my cost to the system and my lost earnings, for example. Suicidal ideation was extreme but now manageable.
The cavalier ignorance and disregard for caution of the medical professions continues to be highlighted in my meetings and conversations with people. I take Zoloft (struggling to taper, what’s new?) and was advised by a Naturopath to take melatonin for the jet lag I had after returning to Australia from the UK last year. I was ok, the melatonin appeared to work and not cause any interaction. However I have been advised by GPs that I can take anything from SAMe to St Johns Wort to HTTP5 in order to substitute for Zoloft in my tapering program.
David, another quote you may find pertinent:
“My patient is lucky to be alive.”
Did the serotonin syndrome leave any long-term side-effects for this person? any PSSD adjacent symptoms such as emotional numbness?