Posted by Elizabeth on April 4, 2002, at 19:01:30
In reply to Re: If both SSRI + MAOI were taken what would happen?, posted by Frankie on March 28, 2002, at 3:06:38
I have some experience with the "serotonin syndrome" (also known as "central serotonin syndrome," perhaps to distinguish it from the bad things which can happen from taking drugs that increase serotonin concentrations in the periphery, such as fenfluramine). After it happened to me I did some reading about it, and I learned some stuff which might be of interest to you if you're curious about this odd and potentially serious interaction (it's almost always associated with two or more drugs that increase serotonin concentrations). I call it the "CSS" for short.
The term "serotonin syndrome" was coined when it was noted that a cluster of symptoms appeared in patients who took fluoxetine in combination with MAOIs (a cocktail which is now considered to be absolutely contraindicated under any circumstances). This is *not* the same as the hypertensive reactions that occur more frequently when patients taking MAOIs eat certain foods (aged cheese, etc.) or take certain drugs (such as amphetamine and pseudoephedrine).
Most serious cases of the CSS involve MAOIs (including reversible MAOIs such as moclobemide) in combination with some other drug. IMO, the CSS is the most dangerous of all the potential food or drug interactions involving MAOIs (hypertensive reactions are pretty easy to identify and treat, while the CSS is difficult to diagnose and there isn't any specific treatment, only supportive measures).
Some of the drugs which can be associated with the CSS are serotonergic antidepressants (MAOIs, SSRIs, Effexor, Serzone, Remeron, clomipramine and perhaps occasionally other TCAs, and yes, St. John's wort), certain synthetic opioids (mainly Demerol and Ultram), MDMA ("ecstasy") and similar drugs, fenfluramine, antimigraine drugs of the "triptan" family (such as Imitrex), and serotonin precursors such as L-tryptophan and 5-hydroxytryptophan (this does *not* mean that it's dangerous to eat tryptophan-containing foods such as milk and turkey, but supplements should be avoided).
There have been isolated cases of the CSS reported involving lithium, antipsychotic drugs, and trazodone (probably others that I don't recall off the top of my head, too). These are extremely rare, though (like, one-report-in-fifty-years rare). It's considered safe to take any of these drugs with SSRIs or even with MAOIs (although the dose of trazodone used in combination with MAOIs is generally low).
Usually it is a combination of two or more of these drugs that triggers the CSS, and while MAOIs are most often involved in serious reactions, there are other combinations that are risky as well. SSRIs and Effexor should not be used in combination with Ultram or Demerol, in particular -- there are plenty of other pain medications to choose from. The cough medicine dextromethorphan should probably also be avoided by people taking SSRIs (it doesn't work very well anyway). In some cases that involve the newer ADs there may be pharmacokinetic factors contributing to the reaction, as some of the new-generation ADs -- notably fluoxetine, paroxetine, fluvoxamine, and nefazodone -- are inhibitors of one or more enzymes in the cytochrome P450 family. When these drugs are used in combination with other drugs, the potential for pharmacokinetic interactions should be taken into account; for example, a migraine sufferer who takes sumatriptan may wish to choose sertraline rather than fluoxetine.
Certain foods (exotic ones, like banana peels (!)) even contain serotonin (not tryptophan, but actual serotonin). Normally, the serotonin would be metabolized in the GI tract by MAO, but in the absence of MAO, the serotonin will be left to its own devices and may travel all over the body wreaking mayhem.
Although the CSS wasn't identified and given a name until fluoxetine came into use, in retrospect it was recognized that there had been some cases of the same syndrome decades earlier when psychiatrists experimented with cocktails that included MAOIs. Today it's become more common as a result of widespread use of the non-MAOI serotonergic ADs.
Like other CNS disorders, the CSS is a fairly amorphous syndrome, but some researchers feel that the symptoms can be divided into four major categories: autonomic, motor, gastrointestinal, and mental status changes. Autonomic symptoms include dilated (sometimes nonreactive) pupils, labile pulse, hypertension or hypotension (sometimes rapid shifting between the two: e.g., blood pressure increases initially, then "crashes;" hypotension may progress to shock), and fever which may progress to malignant hyperthermia. (I believe that in fatal cases, malignant hyperthermia is most often found to be the immediate cause of death.) Motor symptoms include hyperreflexia, rigidity, myoclonus (i.e., twitching), tremor, shivering (chattering teeth seems to be a particularly common manifestation), and nystagmus. Gastrointestinal symptoms can include nausea, vomiting, diarrhea, abdominal cramping, and hypersalivation. Mental status changes can include anxiety, mania, agitation, confusion, delirium, and coma. Some other common symptoms are excessive sweating, rapid and shallow breathing, and seizures. This list probably isn't exhaustive -- like I said, the syndrome is pretty amorphous and subject to much interindividual variation -- but it should give you an idea.
There are certainly plenty of centrally acting drugs that can be used safely in combination with MAO inhibitors. The risk of the CSS is limited to drugs affecting serotonin. Nonserotonergic drugs such as Wellbutrin can be used safely. Some drugs, such as stimulants, may have the potential for causing increased blood pressure (*not* the CSS), but many people can use them safely (monitoring is important here). Some drugs, such as the atypical neuroleptics and the antidepressant trazodone, interact with the serotonin system but do not appear to interact with MAOIs (or if they do, it is very rare and exceptional), and such combinations are commonly used. And of course, plenty of chemicals act as neurotransmitters and aren't affected by MAOIs at all: acetylcholine, endogenous opioids and other neuropeptides, GABA, glutamate, etc.; drugs whose effects are limited to these systems present no special danger when used with MAOIs.
"Serotonin syndrome" isn't a diagnostic category, and there isn't any universally agreed-upon definition (although several attempts have been made to define the syndrome, and in particular to draw the line between ordinary side effects of serotonergic drugs and the CSS).
I'm not sure what the mortality rate is from the CSS, but it's not like it's 100% fatal, or even close. (It's not a very effective way to attempt suicide, if that's what you have in mind.) Still, best not to tempt fate, eh?
-elizabeth
poster:Elizabeth
thread:100678
URL: http://www.dr-bob.org/babble/20020402/msgs/101847.html