Talk:Serotonin syndrome

Changes made

I made several changes and added a footnotes section. Note I forgot to log in and made them as 70.157.54.56, but it was me. Joema 20:14, 31 March 2006 (UTC)

Ondansetron

I would like to challenge what is says in this article about ondansetron contributing to serotonin syndrome. As far as I know all this drugf does is selectivly antagonise the subtype 3 receptor, absolutly nothing to do ith serotonin syndrome. —Preceding unsigned comment added by 82.30.229.218 (talk) 00:29, 2 April 2010 (UTC)

Diphenhydramine?

I'm not a biochemist but the article on diphenhydramine (Benadryl, Unisom, Tylenol PM, etc.) says that it inhibits serotonin reuptake similar to an SSRI. Should it be on the list of medications that can cause serotonin syndrome? I take an SSRI so now that I know about serotonin syndrome I might stop taking my Tylenol PM at night, although I haven't had any problems so far. CBRQ 18:06, 8 June 2006 (UTC)

Don't change any medication you take without first discussing with your doctor. You're right the article on diphenhydramine says that, however I don't see any medical literature indicating serotonin syndrome resulting from diphenhydramine and SSRIs. Drugs affecting serotonin reuptake vary widely in their strength. It's possible diphenhydramine is a very weak reuptake inhibitor or somehow affects only specific serotonin receptors (there are many). The point you raise is logical based on the article wording, but I'd suggest discussing with your doctor. Joema 02:21, 9 June 2006 (UTC)

RE: Here's some medical literature indicating serotonin syndrome from Diphenhydramine as an SSRI with an MAOI: http://meeting.chestpubs.org/cgi/content/abstract/134/4/c4002 —Preceding unsigned comment added by Illuminateur21 (talk • contribs) 10:53, 30 March 2010 (UTC)

Okay, great. Thanks a lot for the answer, I appreciate it. I should be seeing a psychiatrist again in a month or so; when I do I'll try to get an answer about that. CBRQ 01:47, 13 June 2006 (UTC)

It's not biochemist, it's pharmacist, I believe. Either way :P, most over the counter medications will not raise serotonin levels in the brain to levels at which serotonin syndrome is even moderately acquireable. The syndrome simply means youve in a way 'overdosed' on serotonin. Your brain will typically be able to work with these things if you have the help of a psychiatrist, but OTC meds will rarely cause the syndrome if taken at the recommended dosages.--Neur0X ^.talk 19:52, 5 October 2006 (UTC)

I'm quite sure it's pharmacologist, not pharmacist, to which you are referring, Neur0X (I say this as someone with many friends and colleagues in the organic chemistry and pharmacology communities). As for the subject of whether or not diphenhydramine could be responsible for serotonin syndrome, I agree with you, Joema, that there is no extant research to draw upon for inclusion in this article. However, I do know that diphenhydramine was the chemical which inspired the original push to develop SSRIs, starting with fluoxetine (see the History section of the Prozac article for details). Therefore, it seems reasonable to assume that diphenhydramine (and probably other members of the ethanolamine class of antihistamines such as doxylamine) could indeed be causative agent of the syndrome. I'd also like to add that I, too, have been afflicted by severe serotonin syndrome after taking (admittedly larger than recommended) doses of diphenhydramine along with 5-HTP. Wowbobwow12 (talk) 21:40, 2 October 2008 (UTC)

DXM'm manufacturer's insert alerts about the dangers of taking it while on SSRIs. 201.95.194.203 (talk) 00:53, 10 July 2011 (UTC)

Symptoms and mechanisms

I like this article, but I suspect it would be difficult for a layman to distinguish between Serotonin syndrome and simple medication side effects. Maybe one should set out that section more clearly. The reasons why the diffeent drug combinations affect 5-HT should be interesting, I have such a list somewhere and will post when I've found it. That would be a mechanism-based table as opposed to a drug-class table. The mechanism lay-out was easier for me to understand when I first came across this entity. --Seejyb 00:07, 14 August 2006 (UTC)

You are spot on there. Much of the discussion is confusing side effects with serotonin syndrome. The term serotonin syndrome is being used rather loosely in many medical reports, which are often by doctors who are not very familiar with this complex topic. This is why Professor Ian M Whyte (who has done the lions share of original research in this field), and I, advocate the term toxicity. This is meant to emphasise severity: i.e. toxicity = poisoning. That is essentially different to side effects, no matter how distressing those may be to individuals. The term toxidrome is being used increasingly (search the NLM data base) because it describes the picture of intoxication. For some drugs that effect the central nervous system (CNS) the picture is so unique that it is useful to describe it as precisely as possible to aid recognition when it presents. Serotonin toxicity is such a condition and only results from drug over-dose of single drugs, e.g. monoamine oxidase inhibitors like tranylcypromine, or combinations of monoamine oxidase inhibitors with serotonin reuptake inhibitors. I have written a series of explanatory pieces about this that may be seen on my website www.psychotropical.com under the section serotonin syndrome. Signature for aboveKen Gillman 00:11, 21 September 2006 (UTC)

Re serotonin syndrome being hard to confuse with other other conditions: As a thyroid patient, I would like to point out that the named symptoms are also characteristic of hyperthyroidism. Newtonium 12:28, 13 January 2007 (UTC)

Regarding the distinction between Serotonin Syndrome (SS) and Neruoleptic malignant syndrome (NMS): Fever is listed under the symptoms for SS and is also listed under symptoms which are exclusive to NMS. The paper sited (Birmes P, Coppin D, Schmitt L, Lauque D (2003). "Serotonin syndrome: a brief review.". CMAJ 168 (11): 1439-42) has a table listing some key differences between the two and fever is listed there as exclusive to NMS. However, elsewhere in the paper, it does list fever as a symptom of SS. The same paper does provide diagnostic criteria which may be worth including in the wiki, it lists the triad of autonomic, cognitive and somatic signs and symptoms and provides an inclusion criterion of addition of a serotonergic agent and an exclusion criterion of introduction or change of a neruoleptic treatment. --Dr. Doof 18:49, 10 June 2007 (UTC)

Removed from page

The following paragraph was in the actual page, I have removed it here in case anyone would like this information, it was added by 58.87.7.43 which appears to be an IP used by Dr P Ken Gillman.

This table would benefit from being updated, and made more relevant to primary verifiable references, but I cannot see who produced the original table. However, I would comment that almost all the references are secondary or tertiary, rather than primary, this is not ideal for a verifiable account. Perhaps if they would like to contact me I could assist with sources that would increase its direct science base and topicality. by user 58.87.7.43 08:22, 22 September 2006 (UTC)

Mr Bungle 07:37, 17 November 2006 (UTC)

Above is correct assumption, it was I. Ken Gillman 08:35, 26 November 2006 (UTC)

Much of the above is personal experience and has no direct relevance to improving the article. I suggest it would be helpful if such items were removed to avoid clutter and confusion. Can that be done? If so, who might do it? Ken Gillman 08:44, 26 November 2006 (UTC)

Confusing sentence

This very informative article is marred by a confusing sentence:

For example, it suggests mirtazapine, which has no serotonergic toxicity, has no significant serotonergic effects at all, and is not in fact a dual action drug.[12] (Where does the "which" clause end?)

I suggest reformulating it as follows (if this is what is actually intended):

For example, it suggests that mirtazapine (which has no serotonergic toxicity) has no significant serotonergic effects at all and is not in fact a dual action drug.[12] Jedwards05 04:16, 9 March 2007 (UTC)

Carcinoid tumors

It might be interesting to add a rare, but interesting cause of serotonin syndrome secondary to secretion by carcinoid tumors with liver mets. Not sure if its relevant enough for this article, as it is a rare complication. Secretions from carcinoid tumors only become problematic in a small portion of cases. Thanks. EmilioVolz 19:16, 30 May 2007 (UTC)

Drugs which may contribute - revamp needed

This table is incomplete, the categories are vague or even incorrect and some of the drugs are misclassified. Additionally, as part of a new list/table, should we distinguish between those drugs which can trigger SS on their own and those that only cause SS in interactions with other drugs? I'm swamped for time right now, but I'm planning on working to make it an informative and logical table. If anyone else would like to take a swing at it, I'd certainly appreciate it. My suggestion would be to start with eliminating the elicit drug category altogether, as a drug's legal status is not the same thing as it's class and mode of action. Dreadloco (talk) 08:01, 24 January 2008 (UTC)

This is probably the wrong place to report it, but I've experienced serotonin syndrome after taking SAMe, and also after taking a combination of Ginkgo Biloba and Genseng. The second time that I had problems with Gingko Biloba and Genseng it was in a 'healthy' fruit drink I purchased at a local bodega. I couldn't figure out why I had the problem until I went over everything that I'd recently eaten and drunk, and then looked at the fine print of the fruit drink bottle. I've also experienced serotonin syndrome with Wellbrutrin (Bupropion). 4.232.105.24 (talk) 01:56, 13 July 2008 (UTC)

Hunter criteria

Hunter's criteria are apparently quite good in assessing for likelihood of serotonin syndrome. Described here. JFW | T@lk 10:39, 5 February 2008 (UTC)

Older systems include Sternbach's 1991 JFW | T@lk 10:40, 5 February 2008 (UTC)

Ooh look, an NEJM review: 2005 JFW | T@lk 10:43, 5 February 2008 (UTC)

The conclusion of this section as it stands today - "Then the diagnosis is serotonin syndrome. If these are not met then it is not serotonin syndrome." - seems to be in the voice of the Hunter group. Typographically it can easily read as if it is the voice of Wikipedia. Is there a convention to fix this? Thanks! 23:37, 20 August 2008 (UTC) —Preceding unsigned comment added by Douglas Michael Massing (talk • contribs)

Strong statement removed

I've removed the following statement because it appears a rather strong claim to make from a single letter to a journal editor: "The most frequent, and perhaps the only, combination of therapeutic drugs likely to elevate serotonin to that degree is the combination of monoamine oxidase inhibitors with serotonin reuptake inhibitors." Xasodfuih (talk) 15:13, 15 February 2009 (UTC)

Access to PMID 18759711 review

I see it mentioned once in the article, but only with the fact from the abstract. Since it's published in one of "lesser" Expert Opinion journals, I don't have access to it. Anyone reading this having better luck please email me the pdf at my username at gmail. It probably says nothing really new compared to the other recent (and open access) review. Thanks, Xasodfuih (talk) 21:01, 15 February 2009 (UTC)

Mirtazapine

There is sentence about mirtazapine not causing ST based on a review by Gillman, but this is somewhat disputed by Boyer and Shannon. I'm not even convinced that such a detail belongs to this article instead of the article on the drug. Xasodfuih (talk) 22:21, 15 February 2009 (UTC)

Dunkley et al. [1] list some more case studies which associated mirtazapine with ST, but if I'm grokking that paper they seem to say that mirtazapine could not have been the cause for ST in those case reports?! Xasodfuih (talk) 22:34, 15 February 2009 (UTC)

Mirtazapine has a link to an article in which Mirtazapine is used to treat ST

A few changes and suggestions for a FA-level article

I was going to suggest these during the GA-review, but it closed before I had a chance to do so, so I've made the changes myself:

• "no lab tests" in the lede
• say that it's not idiopathic (unlike say neuroleptic malign. syn.)
• say more clearly in there are multiple diagnostic criteria proposed
• give specif. numbers
• Risk: rm Gillman statement (see two sections above)
• newborns: explain
• Gillman's mirtazapine opnion (disputed? see section above)
• 85% of phys. not aware of ST (NEJM)

FA suggestions:

• diff dx: fast/slow onset, give times
• diff between "normal" SSRI side-effects and ST
• survey dx criteria alternatives (mentioned in NEJM but not detailed), especially Sterbach's which still the most commonly used.
• perhaps a diagram of the Hunter "algorithm" fig. 4 here
• severity should be discussed in the dx section according to the 3 Hunter levels
• diff dx to other similar conditions (not just neuroleptic malignant syndrome) (see NEJM)
• list some drug combinations (NEJM doesn't have them)
• the spat about triptan SSRI interaction (FDA letter etc.) see PMID 18957623
• animal models! PMID 17935833 has a review
• neo-natal syndrome: withdrawal vs ST; see JAMA review PMID 15900008

All the best, Xasodfuih (talk) 23:11, 15 February 2009 (UTC)

5HTP and psychological effects

5HTP is a food supplement, a form of serotonin that can traverse the blood-brain barrier. Though not a drug, it can induce the syndrome in high enough quantities. Coincidental with the usual features of the syndrome, psychosis induced by 5HTP may bear a mystical tone. In fact, this frame of consciousness induced by 5HTP and coincidental with serotonin syndrome can become so extreme so as to shut out everything that is not itself. Hence, the sufferer may be self-aware but very estranged from his or her surroundings. 74.195.28.79 (talk) 16:08, 19 March 2009 (UTC)

5-HTP is a drug silly. 71.175.243.53 (talk) 23:58, 11 June 2009 (UTC)

5-HTP is sold without any restriction as a food supplement, at least in Canada (and probably in the US). 70.83.220.148 (talk) 21:05, 9 July 2009 (UTC)

PMID 2035713??

In section 2.1 the article says: "Many MAOIs inhibit monoamine oxidase irreversibly, so that the enzyme cannot function until it has been replaced by the body, which can take at least four weeks.[23]" Ref 23 points to PMID 2035713, which doesn't seem to have any reference to MAO taking 4 weeks to regenerate. I don't wish to change the article, but rather want to learn more about regeneration of MAO, which is very hard to come across as everything I can find is about surpressing MAO. So can the author tell us where he got that info, or make the reference available? A URL here would be fine as well. Thanks, blucat, David. —Preceding unsigned comment added by 198.142.19.124 (talk) 18:25, 21 May 2009 (UTC)

Permanent Nerve Damage

I never would have even heard the term Serotonin Syndrome had it not been for a drug interaction warning from my pharmacist about Tramadol and Axert (migraine med) So I looked it up and sure enough the Tramadol also interacts with my Benadryl, after reading the symptoms I realized that those are the very symptoms that perplexed my neurologists until I finally gave up and quit seeing them. One good thing did come of it. I was placed on Topamax because they suspected absence seizures early on and it did stop the muscle jerks. So that's my question(s) I know I overused the Benadryl as a sleep aid for years, could it have caused permanent nerve damage (all of the symptoms were there they just didn't connect the dots) and will Topamax mask these symptoms? EyorPG

It's unlikely to cause permanant damage. TBH you sound a bit of a worrier. (GimpyFauxHippy (talk) 22:13, 5 December 2009 (UTC))

Mini review

1. Having some difficulties getting much out of the management section. How effective is cyproheptadine? Do we have any evidence and if not this needs to be stated.
2. Treatment section needs some order to it based on either treatment used or disease aspect being addressed.
3. Uptodate refers to cyproheptadine as an antidote. Therefore it needs to be referenced that no antidote exists.[2]

Doc James (talk · contribs · email) 19:51, 23 December 2009 (UTC)

I am not a Dr. but one who has Carcinoid Tumors. Carcinoid tumors that start from the abdominal region produce several hormones including serotonin. Once the tumor metastasized to the liver the serotonin is released to the blood stream and remains until the lungs of liver remove it. These tumors do not release harmones at a steady rate. As the hormones build up within the tumor they are released when the pressure is great enough to break through the cell walls. Heavy lifting, straining, or just a sneeze can cause a release with the following reaction. The reaction depends on how much and what combination of hormones are released.

 This needs to be confirmed by a Dr. who has training and experience with Carcinoid Tumors.

 For those working in EMS and ER rooms follow procedure, look at the blood lab work for metabolic acidosis. This is listed as standard procedure but it is often overlooked. I know from first hand experience.

10/13/2010 Luther Browning BillWilliam (talk) 16:32, 13 October 2010 (UTC)

recent review article

[3] Doc James (talk · contribs · email) 22:55, 12 August 2011 (UTC)

Post-MAOI "washout" time

Hello. In the "Cause" section of the article, right below the table that lists the most common culprits in serotonin syndrome, this sentence can be found: "Many MAOIs inhibit monoamine oxidase irreversibly, so that the enzyme cannot function until it has been replaced by the body, which can take at least four weeks." First of all, the combination of "can take" and "at least" sounds strange to me. It should be either "can take up to" or "takes at least". More importantly though, I don't think four weeks is an accurate timeframe for the reestablishment of full MAO enzyme activity. The source is 20 years old. Basically all sources I know, including package inserts of tranylcypromine and phenelzine, say that MAOI diet has to followed until 14 days after stopping MAOI treatment. This seems to be more or less a consensus. I don't want to edit anything yet, but I was going to ask whether anyone insists on keeping the mention of four weeks. C.d.rose (talk) 20:42, 26 November 2011 (UTC)