New Treatment for Schizophrenia?

[natasa778]

http://www.sciencedaily.com/releases/2013/07/130701080938.htm

…
Famotidine has been used for the treatment of heartburn since the 1980s, but at regular dosing, famotidine almost does not enter the brain at all, since the brain is protected by the blood-brain barrier. By increasing the dosage five-fold the drug is able to enter the brain and affect the histamine system.

"Already after one week the symptoms of persons suffering from schizophrenia started to decrease and after four weeks of treatment the symptoms had decreased statistically significantly. The patients that participated in the study were also positively disposed towards the treatment," says Ekelund.
...

Also small scale trialled for autism http://www.ncbi.nlm.nih.gov/pubmed/11459079

 

[Hip]

Very interesting indeed — although not actually a new discovery, as I notice there are studies on the benefits of famotidine for schizophrenia that date back to the early 1990s.

However, this info on famotidine is certainly new to me, and I am grateful that you posted it, because in addition to having ME/CFS, I also have significant emotional flatness (blunted affect) and anhedonia (anhedonia is the inability to feel pleasure or reward from activities), and both of these conditions are part of the negative symptoms of schizophrenia, which famotidine apparently treats.

The full set of negative symptoms of schizophrenia are: emotional flatness, anhedonia, poverty of speech, lack of desire to form relationships, and lack of motivation.

This 1994 study found that famotidine 20 mg twice daily improves the negative (deficit) symptoms of schizophrenia. The study said that after two or three weeks on famotidine, all schizophrenia patients showed marked improvement in their motivation, and there was an improvement in their symptoms of social withdrawal, low social drive, and poverty of speech (the patients became more sociable, more verbal and more active on famotidine).

So maybe famotidine will help my anhedonia and emotional flatness symptoms. I am definitely going to try it.

There does seem to be a bit of a difference in dose between this 1994 study, and the new 2013 study by Prof. Jesper Ekelund that you cited, Natasa: the 2013 study used a very high dose of 200 mg of famotidine a day.

Interestingly, this 1993 study on famotidine for schizophrenia (they also used 20 mg twice daily) says that other H2 receptor antagonist drugs that penetrate the blood-brain barrier better than famotidine should be tested for schizophrenia as well.



Cimetidine (Tagamet)

Apparently the H2 receptor antagonist cimetidine (Tagamet) crosses the blood-brain barrier more easily than famotidine, so perhaps cimetidine might also work for the negative symptoms of schizophrenia? (But famotidine is 20 to 50 times more potent than cimetidine, so this may make up for the lower blood-brain barrier penetration of famotidine).

Cimetidine is one of the drugs known to be beneficial for ME/CFS.

Cimetidine is antiviral for both herpes simplex virus and herpes varicella zoster virus. Ref: here.

Cimetidine treats interstitial cystitis, a common comorbid condition in ME/CFS.

Cimetidine boosts immune function by reducing T-suppressor cells (T-regs).

Searching this forum, it seems people here take cimetidine for ME/CFS in doses ranging from 100 to 800 mg a day.

For treating herpes zoster virus, the cimetidine dose is 200 mg three times daily, and 400 mg before bed. Ref: here.

For interstitial cystitis, the cimetidine dose is 300 mg twice a day. Ref: here.

For mononucleosis, Dr Jay Goldstein uses cimetidine 300 mg three times a day, for 5 days. Ref: here.

Cimetidine can cause testicular damage in rats, but vitamin B12 helps mitigate this damage. Ref: here.

In Maija Haavisto's ME/CFS book "Reviving the Broken Marionette" (free abridged version here) she writes the following about cimetidine (Tagamet) and ranitidine (Zantac) for ME/CFS:

Cimetidine (Tagamet) and ranitidine (Zantac) for CFS

Ranitidine and cimetidine are antagonists of the H2 histamine receptor. Because of this they are often called antihistamines, though their effects are quite different from the antiallergic drugs (which act on the H1 receptor). They are used to reduce the secretion of stomach acid in ulcer prevention and treatment, but have largely been surpassed by the proton pump inhibitors. They may be useful for allergic symptoms in conjunction with H1 antagonists (“normal” antihistamines).

Dr. Jay Goldstein discovered in the 1980s that H2 receptor antagonists can be very effective against infectious mononucleosis. Because at the time CFS/ME was thought to be a form of chronic mononucleosis, he also tried them in CFS/ME patients, often with good results. He believes the effects may result from the cholinergic and NMDA antagonist properties of the drugs. Devin Starlanyl notes these drugs may be useful in fibromyalgia for promoting stage 4 sleep, especially with amitriptyline.

The H2 antagonists have some immunostimulatory properties. They can be used to treat interstitial cystitis and painful bladder disease. There is some evidence H2 antagonists are helpful for weight loss. They have shown some efficacy in reducing the weight gain caused by olanzapine (an antipsychotic). This might apply to other medications that cause weight gain, as well. Additionally they potentiate opioid analgesia.

According to Goldstein H2 antagonists may cause restlessness and overstimulation in patients with CFS/ME and fibromyalgia. Headache is also possible and rarely may be severe. Occasionally H2 antagonists cause allergic reactions. People with SLE may experience lupus flares.

The H2 antagonists may also increase the requirements of folic acid, vitamin B12 and zinc. Cimetidine may interact with phenytoin, carbamazepine, lidocaine, opioids, theophylline and tricyclic antidepressants. Cimetidine and ranitidine are widely available.

Low doses of cimetidine are available over–the–counter in the United States and some other countries. Ranitidine is available without prescription in the United States, the United Kingdom and Australia.

 

[SOC]

What doses of cimetidine and ranitidine are used to treat ME/CFS symptoms?

 

[Hip]

What doses of cimetidine and ranitidine are used to treat ME/CFS symptoms?

I could not find any official figures, but looking around on the Phoenix Rising forum, doses of 100 to 800 mg of cimetidine daily were mentioned by people.

There is a thread on cimetidine for ME/CFS here.

 

[natasa778]

There is a slight concern imo in using h2 blockers on their own, as might trigger or increase IgE reactivity ...

we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. http://www.fasebj.org/content/early/2005/03/25/fj.04-3170fje.long

Researchers are speculating why - they initially thought it was to do with lowering gastric juices resulting in more IgE reactions as food proteins take longer to digest and stay in the stomach for longer, but if you read the paper the theory does not make much sense, because some proteins that are degraded very fast were still causing IgE. What I think happened there was the h1 – h2 receptor function/expression imbalance:

Effect of histamine antagonists and agonists on IgE production in mice.
Nakazawa T, Umegae Y. College of Medical Care and Technology, Gunma University, Japan.

This study was undertaken to investigate the effect of histamine, its receptor antagonists and agonists on IgE antibody production in mice. BALB/c mice were immunized intraperitoneally with 1 mg alum plus 30 micrograms of Ag90, the antigen of Japanese occupational asthma. Histamine receptor antagonists were administered before the immunization and simultaneous injection of histamine. The mice were bled 14 days after immunization and anti-Ag90 IgE antibody was obtained. Titers of the antisera were measured by passive cutaneous anaphylaxis reaction in Sprague-Dawley rats. Treatment with histamine only did not affect the level of specific IgE antibody. Administration of H1 antagonist or H2 agonist suppressed IgE production significantly. In contrast, treatment with H2 antagonist or H1 agonist augmented the IgE antibody production. Injection of H1 + H2 antagonists had no effect on the antibody production. These results suggest that histamine suppressed specific IgE production via H2 receptors and enhanced it through H1 receptors in the induction phase of the system.

Here is another one http://www.ncbi.nlm.nih.gov/pubmed/6460705

Thus, under these conditions, with these agents, the results suggest that histamine receptors may be involved in modulating the production of reaginic antibodies during a primary immunological response, H1 receptor agonists enhanced, while H2 receptor agonists suppressed the responses, and the reverse effect was observed with the appropriate antagonists. However, histamine receptors appear not to be measurably involved in the development of the secondary reaginic response. (IgG)

So best to take h1+h2 blockers combo, as a precaution, rather than h2 blockers on their own?

 

[anciendaze]

Hip, your list of negative symptoms seems limited to emotions. I think that cognitive deficits are equally important. When you have known someone well before and after onset the loss of cognitive skills is almost as tragic as their misuse due to hallucinations and delusions. Anything which improves cognitive deficits would be of interest to people here fighting "brain fog".

Separate comment: antiviral activity of cimetidine makes me think of another example of off-label use against recent-onset schizophrenia - minocycline. This could be due to antibiotic or antiviral activity, or neuroprotective effects, or immunomodulation via microglia. Unexpected activity of this sort might well carry clues about etiology.
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3121275/

 

[jeffrez]

I'd be hesitant to presume that just because something helps certain symptoms in schizophrenia it therefore would translate to helping those symptoms on their own, without schizophrenia. High dose glycine, for example, has been shown to help the negative sx of schizophrenia, too, but whether that would provide the same benefit to someone w/out schizophrenia is another question. Might even have the opposite effect.

The point about higher doses crossing the BBB is interesting, but again, perhaps that would provide a negative effect in someone w/out schiz. Having said that, considering that so many allergy symptoms often accompany ME/CFS-type of syndromes, it would at least be an interesting experiment. But exercise caution!

 

[Hip]

So best to take h1+h2 blockers combo, as a precaution, rather than h2 blockers on their own?

Thanks Natasa, that's very interesting, and good to know.

I find H1 receptor antagonists (antihistamines) like cetirizine and loratadine are useful for reducing anxiety symptoms anyway, so there would be no problem in taking one of these with a H2 receptor antagonist like famotidine or cimetidine.

 

[Hip]

Hip, your list of negative symptoms seems limited to emotions. I think that cognitive deficits are equally important.

I think the both the positive symptoms of schizophrenia and the negative symptoms of schizophrenia are categorized separately from the cognitive symptoms of schizophrenia. Here is a page that details all the categories of schizophrenia symptoms.

 

[Hip]

I'd be hesitant to presume that just because something helps certain symptoms in schizophrenia it therefore would translate to helping those symptoms on their own, without schizophrenia. High dose glycine, for example, has been shown to help the negative sx of schizophrenia, too, but whether that would provide the same benefit to someone w/out schizophrenia is another question. Might even have the opposite effect.

I think in this game, you are best off adopting an open-minded, "suck it and see", trial and error approach to testing supplements and pharmaceuticals. Many of the medications that I found helped my symptoms I only discovered though trial and error, by trying literally hundreds of supplements and drugs, and noting the ones that worked for me, and the ones that didn't. I have done this slowly, over many years.

Very occasionally I have had very bad side effects (for example, the SSRI drugs I tried immediately precipitated severe suicidal ideation — a known and not uncommon side effect of SSRIs — but fortunately I understood the cause was from the drug, and took no more of the pills).

Interestingly, the best antidepressant and anhedonia treatment I have found is very low dose amisulpride, an antipsychotic drug used (in higher doses) for schizophrenia.

 

[anciendaze]

While listing possible antiviral and antibacterial actions of drugs used for treating schizophrenia above, I left out an important category, parasitic disease. Another pathogen often found in humans is toxoplasma gondii, causing toxoplasmosis.
http://en.wikipedia.org/wiki/Toxoplasmosis

In addition to the antimalarial drugs you might expect (e.g. chloroquine, pyrimethamine), it is also treated with antibiotics: clindamycin, doxycycline, minocycline, tetracycline, spiramycin, sulfadiazine.

Symptoms may well look like depression, anxiety or schizophrenia. Infection can have serious neurological consequences. It can even be a factor in ADHD or OCD. Since about 1/3 of the human race seems to have at least latent t. gondii infection, you might expect this to be one of the first things considered as a possible differential diagnosis.

I am curious about just how many people with mysterious problems called psychological are ever tested for T. gondii antibodies. Anyone here been tested?

Next question: how many studies on the effectiveness of antipsychotic medications have carefully ruled out latent toxoplasmosis? This is especially important as anyone who has read fair number of papers on psychopharmacology can tell you that a drug which shows a positive effect on 30% of psychiatric patients, for which most alternative treatments have poor prospects, is likely to be approved (eventually,) provided it doesn't kill anyone.

 

[searcher]

Has anyone else experimented with high doses of famotodine? I have found thus far that it reduces my brain fog at 80mg a day. I plan to work myself up to 200mg a day to see if that makes a difference.

 

[Hip]

I have ordered some famotidine, and will be trying it soon.

 

[uppercut1991]

Hello, has anyone of you tried famotidine and can share his experience?

 

[Hip]

I bought some, and did some brief tests: I took 40 mg of famotidine twice a day for a couple of days. What I found was that I became extremely vague, and had mildly reduced awareness or consciousness.

This vagueness was different to the normal brain fog you get with ME/CFS. In brain fog, you are kind of aware and conscious at the center, but are lost in the "fog" of you own mind (ie, you are consciously aware, but short-term memory, memory recall, ability to understand things, and ability to make mental connections are slow and impaired, so your are conscious, but a bit lost in your own mental fog).

However, with famotidine I found that my brain fog was not increased, but my central conscious awareness itself was blunted, and I just felt vague and dull mentally.

Famotidine is known to confusion and disorientation as a rare side effect in some people,ᐞ and so I think what I experienced with famotidine was just something akin to this known but rare side effect.

I will try famotidine once more in the future, but if this side effect arises again, then I will have to discontinue it, as the vagueness and dullness of mind famotidine seems to produce in me just makes you sit around doing nothing and thinking about nothing all day.


However, my single negative experience should not put other people off trying famotidine, because I think that this vagueness is just a rare side effect that occurred in me, but will probably not occur in most other people.

So I would encourage others to try.

You need to take famotidine for a few weeks for its benefits to manifest.

 

[ebethc]

I could not find any official figures, but looking around on the Phoenix Rising forum, doses of 100 to 800 mg of cimetidine daily were mentioned by people.

There is a thread on cimetidine for ME/CFS here.

wouldn't this be a really bad idea if you already have low stomach acid? What am I missing? I think a lot of sick ppl have low stomach acid

I have a mast cell disorder (high histamine) so on that front it seems like a good idea, but then I have low stomach acid, so not so much... Also, my fatigue is killing me, so anti-histamines don't seem like a good idea on that front.

 

[Hip]

wouldn't this be a really bad idea if you already have low stomach acid? What am I missing?

Possibly, if you have low stomach acid secretion. Though I can't see why you couldn't easily get around this by taking stomach acid supplements like betaine HCl, or one or two tablespoons of vinegar with your meals.

 

[mermaid]

Re the original study - I was very interested as my son has schizophrenia and has been on antipsychotics for most of his life (he is now 26) as previously he was also diagnosed as a child with Tourette Syndrome, and did in fact take Sulpiride which you mention @Hip that you have taken I think. He is now on depot injections mostly, but I know that the side effects are pretty dire so I wonder what happened over this study and whether it's been more widely trialled?

Interesting too re the histamine comment, as I am realising that many of my own symptoms are probably due to histamine issues at least in part anyway. I have had some of them all my life in one form or another (am now 64).

 

[ebethc]

Possibly, if you have low stomach acid secretion. Though I can't see why you couldn't easily get around this by taking stomach acid supplements like betaine HCl, or one or two tablespoons of vinegar with your meals.

betaine does nothing for me.... I just started taking Urban Moonshine's Bitters (blend of herbs) which is excellent... Vinegar and Fresh lemon juice are good, but not powerful enough for me... Wobenzyme & Serrapeptase are very good, but Wobenzyme is very expensive, so I don't know if it's sustainable... I was on a initial, 3 week high dose, and now I'm stepping it down to see if a "maintenance dose" is still effective..

I upped my SAM-e dosage yesterday, and had dramatically improved digestion! I don't know if SAM-e impacts bile; it might since it's a liver tonic... do you know? maybe it's what I've been looking for..

Anti-histamines make me so tired, and I don't want to do anything that makes me more tired right now... Winter is tough for me. Last: Anti-Histamines are contraindicated for alzheimer's prevention... I'm apoe3/apoe4 so I don't want to take anti-histamines on the regular for that reason, too!

So, the problem is basically High Histamine/Digestion/Alzheimer's Prevention trifecta

 

[mermaid]

Last: Anti-Histamines are contraindicated for alzheimer's prevention... I'm apoe3/apoe4 so I don't want to take anti-histamines on the regular for that reason, too!

@ebethc Somebody on another forum just put me straight on this issue. They say that it's only the 1st generation of antihistamines that are thought to be anticholinergic, not the newer sort that do not make you drowsy. I thought the same as you over this. They sent me this link to research evidence on this aspect https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667286/