Talk:Mirtazapine

Pharmacology contradiction?

In the pharmacodynamics table, the drug is listed as a NET blocker in the micromolar range, but the same section then goes on to state "Unlike most conventional antidepressants, however, mirtazapine is not a reuptake inhibitor and has no appreciable affinity for the serotonin, norepinephrine, or dopamine transporters...". I notice that the NET affinity is an order of magnitude at least lower than the receptor affinties listed. I haven't changed anything though because this isn't my subject and that K_i value may well be insignificant at the drug's normal dosage, but it still sounded like a possible mistake to me. Psymun (talk) 19:14, 22 March 2011 (UTC)

Also pharmacodynamics "Mirtazapine is an antagonist/inverse agonist..." then the following paragraphs proceed to only mention antagonism. its either an antagonist or an inverse agonist it cant be both — Preceding unsigned comment added by Dimesnake (talk • contribs) 22:47, 11 September 2011 (UTC)

Factual error in Interactions section:

Interactions paragraph states: "As a serotonin receptor antagonist, mirtazapine will not cause serotonin syndrome at any dose"

I am taking Mirtazapine and the inbox leaflet for "Mirtazapine 15, 30 and 45mg Orodispersible tablets" produced bt Teva UK ltd (leaflet last approved feb 2009) clearly states: (copied exactly as written in leaflet) If you experience a high temperature, muscle stiffness or twitching, confusion, irritabilty and extreme agitation, you must contact your doctor immediately as these symptoms may be an indication of so called seretonin syndrome. Although this syndrome only occurs very rarely, it can be life-threatening.

Forgive me if I've done something in error but I thought a life-threatening consequence needs correcting. 94.10.21.251 (talk) 12:17, 17 March 2010 (UTC)

I believe that is a standard boilerplate warning that goes with all anti-depressants. Sort of like how with Vyvanse, a sustained release amphetamine, there are instructions not to chew or crush the pills, something that makes no sense b/c vyvanse is already a powder and it is a pro-drug so crushing it doesn't cause it to be released into your bloodstream any faster. Pharmacists are stupid -- anyone with an eighth grade education could do their job. Pharmacists tend to have blind faith re: the package insert, not knowing enough about the underlying science to challenge something that is obviously wrong. Once I had a pharmacist try to not dispense seroquel until checking with my doctor b/c of a supposed risk of serotonin syndrome. I was able to browbeat him into just giving it to me without checking, because the concern was silly and unfounded, but the guy was just following the written instructions like a mindless robot.

In any event, if you see my post below, I think that the section on serotonin syndrome is inaccurate... but probably only at the margins, and certainly not based on "evidence" provided by the package insert...PStrait (talk) 22:52, 5 June 2010 (UTC)

According to Hexal (a Mirtazapine manufacture) mirtazapine should not be taken with any MAOIs and should be used only carefully with SSRIs and venlafaxine(i.e. Effexor). Recently I started taking 15mg mirtazapine with my daily dose of effexor and after only 2 doses of mirtazapine I showed strong symptoms of Serotonin Syndrome. Do not use wikipedia as a safe source for medical information and always the package insert. It is NOT just standard BS as some might have you believe — Preceding unsigned comment added by 212.242.226.71 (talk) 16:17, 1 July 2011 (UTC)

To the poster above, you shouldn't crush Vyvanse because it can make you nauseous. — Preceding unsigned comment added by Astrohoundy (talk • contribs) 09:29, 5 December 2011 (UTC)

Serotonin Syndrome

The section on serotonin syndrome is wrong, at least at the margins. For example, you can see a case of serotonin syndrome in which mirtazapine (along with olanzapine and tramadol) is partially implicated here: http://www.theannals.com/cgi/content/abstract/38/3/411

Also, I found a case study of a woman receiving only mirtazapine as a monotherapy who developed serotonin syndrome: http://www.ncbi.nlm.nih.gov/pubmed/12671522

I'd edit here, but I don't feel like I have enough expertise to get it right or to judge how rare the above kind of exception is. Does anyone know more about this, and if so would you be willing to revise this paragraph? PStrait (talk) 22:47, 5 June 2010 (UTC)

Regarding the first source, they clearly concluded that Tramadol was the likely cause of serotonin syndrome when taken alongside Venlafaxine: "An objective causality assessment revealed that the addition of Tramadol was the probable cause of the adverse reaction.". Tramadol is a serotonin releasing agent, among other things, and shouldn't be taken with SSRIs or SNRIs as far as I know. The second source cites the woman as being "an individual with risk factors for hyperserotoninemia resulting from reduced, acquired endogenous serotonin metabolism." So that looks like a rare one off. If anything these should maybe be incororated into that section stating that in very rare or exceptional cases mirtazapine has been linked to serotonin syndrome? Rather than as proof. Even then, that first case when taken alongside Tramadol and Venlafaxine proves nothing at all. For all we know, that person may have had less severe serotonin syndrome due to being on Mirtazapine as well. There's nothing conclusive either way.

The bottom line is, Mirtazapine has no effect on serotonin reuptake and actually blockades a number of serotonin receptors, so it's widely considered not to be a risk when taken with other serotonergic drugs. I take Mirtazapine and I can tell you that, on the clinical level, it isn't considered to be a risk at all. I also take Sumatriptan for Migraine alongside it and have done for years, something you'd be forbidden to do if on an SSRI. I have spoken to a couple of GPs about it and they all consider it safe. Not to mention that some Psychiatrists will prescribe Mirtazapine alongside SSRIs. So, if this perception of it being safe from a possible contributing factor to serotonin syndrome is wrong, then it's far more than just a wikipedia article that would be at fault. --Kerans (talk) 13:05, 17 September 2011 (UTC)

According to Hexal (a Mirtazapine manufacture) mirtazapine should not be taken with any MAOIs and should be used only carefully with SSRIs and venlafaxine(i.e. Effexor). Recently I started taking 15mg mirtazapine with my daily dose of effexor and after only 2 doses of mirtazapine I showed strong symptoms of Serotonin Syndrome. Do not use wikipedia as a safe source for medical information. — Preceding unsigned comment added by 212.242.226.71 (talk) 16:11, 1 July 2011 (UTC)

Removal of "opioid activity" addition

I've removed this for several reasons. The first reason is because the editor makes it sound like mirtazapine directly binds to and activates the mu-opioid receptor, and this is most certainly not the case. Secondly, he leaves out that it also interacts with the kappa-opioid receptor, which in general tends to have negative effects on mood. Finally, I have an issue with the study referenced itself: it tests the antinociceptive effects of mirtazapine (as well as venlafaxine) and concludes that they are, at least in part, mediated by the endogenous opioid system. Then they go on to suggest that some of the antidepressant effects of mirtazapine (and venlafaxine..) may be mediated by the opioid system as well. However, there is absolutely no indication in my opinion that this is actually the case. The fact that mirtazapine produces antinociceptive effects through the opioid system is in no way indicative that it also produces antidepressant effects through the same system. Pain and mood pathways in the brain are totally separate; because you affect one does not mean you will necessarily affect the other. I find it silly that the authors of the study would suggest what they did, and thus, I have a problem with that information being added to Wikipedia, especially in the way that the editor presented it. el3ctr0nika (Talk | Contribs) 00:27, 1 September 2010 (UTC)

Where does the 'common knowledge' that "the kappa-opioid receptor ... in general tends to have negative effects on mood" come from? Salvinorin seems to be the most widely used/abused kappa-opioid agonist that I'm aware of, and anecdotally, it can as easily have either a "paradoxically" positive effect on mood or little subjective effect (though it is also very short-acting, so finding out whether any positive effects on mood are directly mediated or based on a 'rebound' mechanism is of interest to me). Are there some references to other selective kappa agonists showing a clear effect, or is this one of those things being punted around from general opiate research, where kappa-mediated effects might be unpleasant when combined with (withdrawal from?) mu-mediated ones? Just curious. --64.252.204.108 (talk) 10:22, 19 November 2010 (UTC)

Mirtazapine and paralysis

Neurological symptoms may happen while taking mirtazapine. This should be stated.(strange it is not mentioned and developed) On Jun, 25, 2011: 9,884 people reported to have side effects when taking Mirtazapine. Among them, 18 people (0.18%) have Paralysis.(http://www.ehealthme.com/ds/mirtazapine/paralysis) It is also reported in http://www.druglib.com/adverse-reactions_side-effects/mirtazapine/seriousness_disabling/ Often (but not always it seems) the condition is triggered by an association of mirtazapine with other drugs ( 1. Depromel 2. Rohypnol 3. Remeron 4. Vegetamin b 5. Lexotan) What I would like to know is if this paralysis is reversible or not. (Nothing being mentioned, I suspect irreversible) — Preceding unsigned comment added by 109.89.68.228 (talk) 18:04, 12 July 2011 (UTC)

Mirtazapine is not a Tetracyclic

Mirtazapine is classed as an atypical antidepressant, but more specifically as an Alpha 2 antagonist; NaSSA (noradrenaline and specfic serotonergic agent); dual serotonin and norepinephrine agent; antidepressant. This needs to be changed in the first paragraph talking about Mirtazapine's class.

Reference: Stahl, Stephen M. MD, PhD. "Essential Psychopharmacology: The Prescriber's Guide". Cambridge University Press, 2006. On Page 325. —Preceding unsigned comment added by 69.133.155.151 (talk) 23:38, 5 February 2011 (UTC)

What?-of course mirtazapine is a tetracyclic-it can, of course be described in other ways-but it has four ring systems, therefore, it is chemically a tetracyclic. Being "tetracyclic" does not infer any specific mode of biological activity, it is just a chemical classification. Dehughes (talk) 01:11, 26 October 2011 (UTC)

Ineed, it is both a TeCA and a "NaSSA", the former describing its chemical structure, and the latter describing its pharmacological profile. el3ctr0nika (Talk | Contribs) 03:18, 27 October 2011 (UTC)

Primary research

This article like all others should be based on review articles not primary research. Doc James (talk · contribs · email) 14:32, 11 July 2011 (UTC)

We have issues with the POV of this article for example we say it is useful for itching yet support this only with primary research (one study looked at only 4 patients, the other was a pilot). One cannot draw this conclusion based on the evidence provided. Thus the POV tag.--Doc James (talk · contribs · email) 05:33, 21 July 2011 (UTC)

I think that parts of this must have been written by drug reps or something. The sentence about mirtazapine not causing serotonin syndrome is pure rubbish; if you type the words "mirtazapine" and "serotonin syndrome" into Pubmed or the like, you will find many incidences of serotonin syndrome caused by mirtazapine monotherapy and in combination with other drugs. Hopefully PStrait from above reconsiders what (s)he says, and perhaps does some research into exactly how mirtazapine works before offering dangerous advice. Chairman Xi (talk) 12:18, 24 August 2011 (UTC)

"Any (over)dose, no serotonin syndrome" has been removed as unsourced wikiality. Alessandra Napolitano (talk) 04:48, 17 November 2011 (UTC)

I'm a bit wary of claims that relatively recent drugs have no longer term adverse effects or withdrawal issue, have to be pragmatic, we don't really know but there's no obvious reason to suspect a big problem. That said it was over ten years after SSRI medication became available before the discontinuation issue was acknowledged, and I've got personal experience of the dependency/withdrawal problems Tramadol can deliver, that being another drug that was supposed to be free of such things until it turned out not to be. Got to be very careful about confidently asserting something is safe or free of a problem, especially if even the drug company/pharmacist/GP is being cautious. Well, more importantly, as someone above said, don't get your medical advice from wikipedia! — Preceding unsigned comment added by 94.8.124.250 (talk) 18:31, 1 September 2011 (UTC)

The article contains a good deal of synthesis from primary sources, like binding assays, rat and mouse experiments. I have added the species in such cases and added fact tags. What we need is not conjectures by the editors from a variety of speculative primary sources and lab experiments, but peer reviewed clinical review articles. Otherwise such results belong into a separate section "animal and cell research", not with a discussion of clinical pharmacology, if at all into the article. Ihave also deleted a self-published ref due to WP:MEDRS, regardless who the researcher is. 70.137.154.143 (talk) 21:27, 22 September 2011 (UTC)

Wouldn't it be nice if we had review articles to support every single point? Because this is a narrow topic (not like, say, selective serotonin reuptake inhibitor), we can't, and won't. Reviews are preferred, but where unavailable, or not yet found by editors, we have the sources we have. Rest assured that academic peer review normally doesn't let any sort of nonsense be published in respected journals, Sokal affair notwithstanding. Alessandra Napolitano (talk) 04:48, 17 November 2011 (UTC)

Side Effects - on the packaging but not in the article.

I've got the package leaflet here .. seems to date to 05/10 with Aurobindo/MilPharm/APL being behind it. A package leaflet, I presume, is less than ideal as a reference but still. In the way of the more modern leaflets of this type its fairly specific about the incidence of side effects, definging what they mean by Common/Rare etc. Reason I was motivated to post was I've just moved to this medication from an SSRI and had a fairly grotty hit of side effects, amongst other things lower back pain, joint pain and muscle pain. According to the aforementioned leaflet, this is seen in between 1 and 10 users per 100, which it describes as "common". I've added the conditions as appropriate, with a citation needed tag as I suspect it needs someone with (a) proper access to PubMed and (b) the training needed to interpret what is published.

I was prescribed with this medication in March 2011 and has stopped few weeks after. As a sideeffect, I lost my emotions and have trouble with my regular bowel movement. As if, every nerve connected to my brain has been disconnected. I felt there was like a feeling of numbness all over my body, it was like a place where gradually water is flowing which means, losing my feelings all over my body one at a time. And fr then on, i always feel cold whereever i am... I always have goosebumps where ever I am. — Preceding unsigned comment added by 99.234.203.160 (talk) 19:18, 18 September 2011 (UTC)

There's probably other discrepancies, but I don't want to rewrite that bit of the article unless someone Pharmy-ish wants to help! — Preceding unsigned comment added by 94.8.124.250 (talk) 17:54, 1 September 2011 (UTC)

Overdose section somewhat misleading?

"Overdose with as much as 30 to 50 times the standard dose has shown to be relatively non-toxic. One case in which 1,200 mg was ingested proved non-fatal." seems a little misleading to me, since it sounds like 1,200 mg should be more than 50 times the standard dose, which isn't the case, unless "the standard dose" is the smallest available tablet, which seems very unlikely. Thoughts on simply removing the second sentence, and having two citations for the first? Cheyinka (talk) 22:41, 4 September 2011 (UTC)

Adverse Effects

This section is written very poorly. Half the points have no citation and some claims reference sources which say nothing about the point in question. Take this line from the second paragraph: "This is probably due to the loss of efficacy of the drug over time, as tolerance develops with long-term use. [28][37][38][39]". Correct me if I'm wrong, but I see nothing in any of those four sources that state the drug's efficacy decreases over time or that people "develop a tolerance". In fact, that is a ridiculously bold and, I would argue, fictitious, claim. It's also not clear whether they mean the drug's general efficacy or just relating to those side effects mentioned before. It's a sloppy sentence and should be rewritten or removed. --Kerans (talk) 12:37, 17 September 2011 (UTC)

Done. This section mixes invention and fact, unattributable adverse events with confirmed adverse drug reactions. Needs to be changed into "side effects" and sourced to appropriate MEDRS source, rather than conjectured from the raw data, due to synthesis. Have removed a few which have been added over time and seem not to be supported by refs. 70.137.148.24 (talk) 06:29, 23 September 2011 (UTC)