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Zofran (Ondansetron)

Cetkat
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Cetkat

Cetkat

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Is anyone on this medication regularly? It's normally an anti-nausea/vomiting med. Someone I know takes it and it was mentioned, so I casually looked it up on wiki.. as I was just wanting general stuff. However....

http://en.wikipedia....iki/Ondansetron

Take a look.

It has some crazy psych applications!

  • Avoiding and reversing TD
  • Treating Parkinson's* (Ok, not exactly psyc.. but relevant since the treatment for it is a Dopamine Agonist)
  • Removing cravings like alcholol, which I've often seen mentioned as an issue surrounding increased Dopamine (along with things like gambling, etc..)
  • Treating negative Schizophrenia symptoms
  • Treating OCD

All of this with a 5-HT3 Antagonist that doesn't (apparently) seem to have any Antagonistic/Agonistic properties on Dopamine.

Frankly... It sounds *way* too good to be accurate. I haven't gotten the chance to look into these claims to any extent.. my day has been kinda hectic/all over the place. So I don't know anything else yet. I'm planing to do some research on the various studies and see for myself.

However.. I figured it couldn't hurt to go ahead and ask for thoughts/opinions/ideas concerning this, abet a bit prematurely.

So, does anyone have any knowledge or links they'd like to share?

Interestingly enough.. I saw nothing about it affecting depression negatively, although I have no idea if if the antidepressant meds utilize 5-HT3 to work, or if it's primarily others (5-HT1, possibly??).

It certainly is interesting at any rate...

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Cetkat

Cetkat

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Isn't that for nausea? I think I've got some right here on the table beside me. Yep. Just looked. It's Zofran. It didn't do squat for my nausea. I tried it several times when I was in the hospital and a couple of times at home. I was to put it under my tongue and let it dissolve. They are 4mg tablets. Honestly, I don't know how it would work for anything else but for nausea, it didn't do jack.

Yep. And, although I kinda do actually need a nausea med for now and then.. my interest is solely on the other supposed applications. However, that probably only shows up with stable usage for a certain period of time.

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Cetkat

Cetkat

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You can look up the mechanism of action for most meds on RxList btw.

Hmm, yeah.. that's right. I do look at them often. They tend to have some pretty detailed info. I'll try them, thanks!

Update: Well, not much there except for this:

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist.

That, and the side effects listed in my Epocrates App (that I was going to look into) of EPS/Dystonia have no proven causation.

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Cetkat

Cetkat

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Hey, I don't take it every day but probably 3-5 times a week. I take an 8mg tablet. I take it for nausea.

I would take it more frequently if it wasn't such a pita to get extra from insurance.

Any particular side effects or benefits that you can think of? Or lack of problematic side-effects from other stuff that could be related?

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Cetkat

Cetkat

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Study on REM induction decreasing with 5HT-3 Agonists, and mitigation of this with Ondansetron. Supports a dopamine link.

http://www.ncbi.nlm....pubmed/18295951

Study on positive anti-depressant effects of a melatonin agonist. When combined with Ondansetron, the anti-depressant effect was heightened.

http://www.ncbi.nlm....pubmed/15069466

Ondansetron improving depression alone, but the study group was limited to alcoholics.

http://www.ncbi.nlm....pubmed/14634493

More on link between 5HT-3 and Dopamine. Kinda vague, but the main point is that Ondansetron doesn't affect the "dopaminergic synapse directly"

http://www.ncbi.nlm..../pubmed/8383982

Successful treatment of bradykinesia and catalepsy EPS induced by Haldol

http://www.ncbi.nlm....pubmed/20813116

Successful reversal of TD induced by Haldol

http://www.ncbi.nlm....pubmed/11408032

Treats negative symptoms of Schizophrenia

http://www.ncbi.nlm....pubmed/20516364

"Ondansetron combined with haloperidol produced a significantly greater improvement on PANSS overall scale and subscales for negative symptoms, general psychopathology, and cognition at endpoint compared to placebo with haloperidol. Patients in adjunctive ondansetron therapy also experienced significantly lower incidence and severity of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac, and gastrointestinal side effects."

http://www.ncbi.nlm....pubmed/16959472

"ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed."

http://www.ncbi.nlm..../pubmed/7855229

Talk of possible beneficial link between Ondanetron and Psychosis.

*Note: Still need to look at actual study. Abstract is too vague.

http://www.ncbi.nlm....pubmed/10227604

Ondanetron and Zyprexa (olanzapine) have similar affinity level for 5HTP-3 Antagonism

*Question: Could Ondanetron boost another AAP to create a more similar reaction to Zyprexa use without the blood sugar issues?

http://www.ncbi.nlm....pubmed/11711053

Clozapine's antagonism of 2-methyl-serotonin's stimulation of phosphoinositide hydrolysis can be successfully attained by Ondanetron (*this would be without side effects). Haldol and Thorazine do not achieve this antagonism.

*Possible reason for additional Clozapine effectiveness over Haldol/Thorazine?

http://www.ncbi.nlm..../pubmed/1677603

More on mechanism of action:

"Blockade of central 5-HT3 receptors does not result in alternations in metabolism of DA or 5-HT in major ascending dopaminergic areas" http://www.ncbi.nlm..../pubmed/2530097

DA: http://www.ncbi.nlm....pubmed/12603267

Increased acetylcholine release: http://www.ncbi.nlm..../pubmed/8814902

Interesting stuff. Seems to support everything. Thoughts / Reactions?

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ChemistryExperiment

ChemistryExperiment

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i actually notice i have better control over limiting compulsive ocd behavior when i take it for a while straight.

I am supposed to be on reglan or domperidone. Domperidone isn't available in the USA, however i could order it from canada. The problem is it can cause lactation and things and so its a no go. Reglan, I can't take because it causes almost immediate TD.

I have some sort of neurological tic/tremor thing going, and it does seem to help that as well.

I wish i could get more of it per month. I think when I see my GI doctor next I am going to ask him for a larger script and to do a prior auth. Because it would be worth it to take it every day and not have to deal with the symptoms it treats GI wise, and have to pick and choose which days are worse.

I love it, actually. I don't think i have ANY noticable negative side effects.

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notfred

notfred

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The vet used it on my cat when they were having to force re-feed her. She had a lot of GI upset and Zofram worked. There was not anything but brand Zofram then and it was quite expensive.

Lots of anti-nausea meds were psyco meds in another life, Reglan (Metoclopramide) is a phenothiazine and Thorazine is used for its ant-nausea effects. A lot of the AP's have anti-nausea effects.

So it is no surprise Zofram could have some MI applications.

nf

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Cetkat

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The problem is it can cause lactation and things and so its a no go.

I actually just came across an older study that 6+ months use of Lithium can actually decrease prolactin by about 40%. As far as I know.. there are no studies that compare prolactin levels with an APP alone vs co-administration with Lithium. May be nothing, but I'm posting it for your consideration. I have the study if you want it.

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null0trooper

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Interestingly enough.. I saw nothing about it affecting depression negatively, although I have no idea if if the antidepressant meds utilize 5-HT3 to work, or if it's primarily others (5-HT1, possibly??).

5-HT1 and 5-HT2 are the primary receptor systems of interest for depression, addiction, psychosis, etc., although they obviously only account for part of the story. Oddly enough, it looks like 5-HT3 is one of the few receptors that amitriptyline doesn't bind to.

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Cetkat

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Interestingly enough.. I saw nothing about it affecting depression negatively, although I have no idea if if the antidepressant meds utilize 5-HT3 to work, or if it's primarily others (5-HT1, possibly??).
5-HT1 and 5-HT2 are the primary receptor systems of interest for depression, addiction, psychosis, etc., although they obviously only account for part of the story. Oddly enough, it looks like 5-HT3 is one of the few receptors that amitriptyline doesn't bind to.

Hmm.. so do you know of any AD's/AP's/AAP's that have an affinity for 5-HT3?

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  • 1 year later...
CirclesOfConfusion

CirclesOfConfusion

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It has some crazy psych applications!

  • Avoiding and reversing TD
  • Treating Parkinson's* (Ok, not exactly psyc.. but relevant since the treatment for it is a Dopamine Agonist)
  • Removing cravings like alcholol, which I've often seen mentioned as an issue surrounding increased Dopamine (along with things like gambling, etc..)
  • Treating negative Schizophrenia symptoms
  • Treating OCD

All of this with a 5-HT3 Antagonist that doesn't (apparently) seem to have any Antagonistic/Agonistic properties on Dopamine.

Frankly... It sounds *way* too good to be accurate. I haven't gotten the chance to look into these claims to any extent.. my day has been kinda hectic/all over the place. So I don't know anything else yet. I'm planing to do some research on the various studies and see for myself.

Hmm, I guess I didn't read far enough into the med info for that VERY relevant nugget to stick in my head! I was on odansetron for a few weeks last year as an anti nausea adjunct to vicodin. Any differences I felt for any reason I mainly attributed to either the vicodin or the underlying reason for taking that. All I remember was that the pill tasted minty. The quoted possible applications above ^^^ are interesting to me since one of my longtime meds is wellbutrin. There are so few other dopamine-related options so I'm all ears for new information that might be helpful in case things need to change.

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gizmo

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I get horrid akathesia on compazine (10x worse that abilify) and they had to tie me to the bed when they gave me phenergan, but I tolerate zofran extremely well. It's my nausea drug of choice. I always have some in my cabinet for when I get nausea associated with migraines.

I've never noticed an interaction between it and my mental meds, but normally if in sick enough to need a zofran, I take a night off the mental meds (it's amazing at what 12 pills will do to an upset stomach!)

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  • 1 year later...
Cetkat

Cetkat

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Update:

 

So, I don't recall these showing up in the pubmed results before:

 

http://www.ncbi.nlm.nih.gov/pubmed/23680574

http://www.ncbi.nlm.nih.gov/pubmed/23140020

http://www.ncbi.nlm.nih.gov/pubmed/23112413

http://www.ncbi.nlm.nih.gov/pubmed/22171087

 

I couldn't help but notice that # 2 and 3 have the same pA2 value (whatever that is) to Zofran... and therefore, may actually be the same chemical/medication?

 

Correct me if I'm wrong... but did companies take the Zofran antidepressant results and create their own novel medication rat trials?

 

Cause if they did, that means a shit-load.  Especially since they're recording positive results across the board.

 

I also found a study about how Zofran cures SSRI nausea.

http://www.ncbi.nlm.nih.gov/pubmed/22298739

 

So if you're suffering of said dilemma, pounce on that.

 

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HAL9000

HAL9000

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Not a lot to add but its also my nausea drug of choice.   I think its the only thing I have ever taken that evaporates into thin air if you open the foil packet.

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melissaw72

melissaw72

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It's pretty impressive in its nausea killing abilities, but gives me a pretty bad headache. I think I like phenergan a little better.

 

It did to me too, but I found that the more I took it, the headaches went away. 

 

If I take it at this point, I don't get headaches, and I take it maybe twice/week (and have been since maybe last May or so).

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  • 6 months later...
Cetkat

Cetkat

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Well, what do ya know....
 
 
"Brintellix"
12.1 Mechanism of Action

The mechanism of the antidepressant effect of vortioxetine is not fully understood, but is 
thought to be related to its enhancement of serotonergic activity in the CNS through inhibition 
of the reuptake of serotonin (5-HT). It also has several other activities including 5-HT3 receptor 
antagonism and 5-HT1A receptor agonism. The contribution of these activities to vortioxetine’s 
antidepressant effect has not been established.

 

 

My Mayo pdoc was impressed with this one.  I didn't know why.... now I do.

 

They made an SSRI with the Zofran antagonism!!  And it passed FDA!

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jt07

jt07

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If anyone could look up the affinities and compare the antagonism, I'd be very grateful.

 

I'm very interested to know if this is an SSRI with a bit of Zofran or Zofran with serotonin reuptake thrown in!

 

It appears that Zofran has an affinity for 5-HT3 of Ki = 1.6 nM and Brintellix has an affinity for 5-HT3 of Ki = 3.7 nM. Since lower values mean higher affinity, Zofran has a relatively higher affinity for 5-HT3 by more than a factor of 2. However, they both have very strong affinities (from my reading, anything lower than 10 is a very strong affinity). So there you have it and can make of it what you will.

 

http://pubs.acs.org/...rnalCode=jmcmar

http://en.wikipedia....ki/Vortioxetine

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Cetkat

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Thanks for the insight!  It sounds relatively close to me.  I suppose one take away is that the Brintellix could end up being able to do what the Zofran seems to be able to do in the area of depression;  while the alternative would be that the difference matters, but it would take far less of the Zofran to achieve the study results.

 

An old pdoc told me of studies that showed that SSRI's lowered dopamine levels over time... so that could be a flaw of grouping the HTP3 antagonism with an SSRI -- but at the same time, studies have shown that Zofran doesn't actually raise or lower dopamine levels.  It impacts them in another way that isn't clear.  I think it will be curious to see how Brintellix gets rated against the other SSRI/SSNI options in the future.

 

Now I guess the question is, if it can be added to a depression med and maintain its effect... could it also be built into an AAP type med to not only allow for BP individually to take it & receive the same anti-depressant effect, but also perhaps offset the risk of TD?  If it doesn't change dopamine levels & can reverse haldol TD affects (to an extent) without inducing schizophrenic symptoms - I don't think it's too far off that if combined, it could have some sort of protective feature.

 

I hope they end up studying that in the future as well.

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callmecrazy

callmecrazy

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It's great for nausea and used all the time in the hospital -- the go to nausea drug. I've never seen any untoward side effects and it works famously. No sleepiness, etc. I've never heard of the other benefits mentioned. But if anybody is having nausea with their psych meds, ask for a script for zofran. No sense in suffering.

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Cetkat

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It's great for nausea and used all the time in the hospital -- the go to nausea drug. I've never seen any untoward side effects and it works famously. No sleepiness, etc. I've never heard of the other benefits mentioned. But if anybody is having nausea with their psych meds, ask for a script for zofran. No sense in suffering.

 

Agreed.  I have an rx for it for nausea, and I feel it's superior to the AP variety by far - with zero side effects.    I haven't taken it in the way that has the potential to help with mood, but I find the research fascinating none-the-less.  Especially since, after I initially made the post... researchers have extended the (lower-theory-research) into new drug treatments.

 

I will add, that I read on a pregnancy forum (over and over again), that adding 0.5mg of zanax (I suppose other benzos could work too) - to the Zofran at the same time  -- dramatically increases it's effectiveness as an anti-nausea med without any other side-effects.

 

As I had a separate prn script for Zanax, I gave it a try when the 8mg Zofran didn't stop the nausea -- and low and behold, they're right.  I told my pdoc, and he was pleasantly surprised (he's never worked in OB GYN, so that bit was out of his range of experience), but he was curious and gave me his blessing.

 

So, considering that many of us have benzo scripts anyway... should nausea become and issue and Zofran is tried - it would be something to attempt if the 4/8mg doses prove less than effective.  My result of adding just that small amount of xanax was dramatic.

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crtclms

crtclms

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I got IV Zofran for when I was getting infusions of di-hydro-ergotamine to prevent vomiting. Everyone knew I am bipolar, and were aware of the other meds I was on, and they didn't seem to be concerned about it affecting my mood. My pain Dr was an anesthesiologist, so she knows drug interactions pretty well.

 

I also take tablets of Zofran before I take migranal, which is di-hydro-ergotamine at a much lower dose. But I have pretty much given up on both Imitrex and Migranal. I might do the transfusions again.

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