The Anti-depressant, Brain Fog, and Histamine Intolerance Connection

November 20, 2014  |  Blog, Drug Intolerance, Histamine Intolerance

The anti-depressant, brain fog, and histamine intolerance connection, is another poorly understood area.

Drug intolerances are extremely common with histamine intolerance yet there is still much that is not known. Does histamine intolerance result in drug intolerance, or do drug intolerances trigger histamine intolerance in some people? We simply do not know.

We do know that:

Beyond that there is still much work to be done. In the absence of clinical trials, we are left with clinical observations of medical professionals, working on the cutting edge in clinical practice.

This post looks at the medical hypothesis of Professor David Healy, a psychiatrist, and psycho-pharmacologist, with an active interest in adverse drug reactions to psychotropic drugs. Here are some of his interesting clinical observations relevant to histamine intolerance:

Histamine De-stabilisation

Professor Healy concludes that many anti-depressants are not “clean” but interfere with the anti-histamine system.

He states that SRI withdrawal can be viewed as a “histamine over-activity (semi-allergic) state brought around by the fact that the person has been on anti-histamines chronically.”

This hypothesis fits with the emerging hypothesis that the anti-histamine system is normally a tightly controlled process. H1R and H4R are thought to be pro-inflammatory and initiate an immune reaction. H2R and H3R are thought to be anti-inflammatory and halt an immune reaction. The long-term use of anti-histamines, for example, is thought to alter the equilibrium of this tightly controlled immune system. Chronic anti-histamine use is also thought to trigger IgE allergies, and food sensitivities, which are a common with SSRIs.

Professor Healy’s protocol for withdrawal of SRIs, predominantly includes tapering off with anti-histamines and mast-cell stabilisers, to continue to compensate for this dis-equilibrium in the anti-histamine system.

It is interesting to also note that anecdotally people who have been on anti-depressants, and have severe adverse reactions, report that have a lifelong increased sensitivity to pharmaceutical drugs. That is, whilst they may be able to withdraw from anti-depressant medication, the introduction of new medication, will often see a return of their old withdrawal symptoms. This suggests a pervasive destabilisation of the histamine system in some individuals.

Brain Fog

Brain fog (or mental fog, meta–memory, or chemo-brain) is common with histamine intolerance.

I have had the opportunity to have a detailed discussion and private correspondence with Professor Healy on the connection of brain fog to prescription medication (and indeed SSRIs, statins, fluoroquinolone, antibiotics, and other drugs).

Interestingly, Professor Healy concludes that brain fog is caused by muscle memory disruption. That is; brain fog is not in all in the mind, but actually in the muscle.

This hypothesis is founded on the fact that brain fog is often accompanied by myalgia, that many drugs interfere with muscles, and the research into statin drugs where “it is conceded for example that the statin group of drugs can cause severe cognitive problems, up to apparent dementia levels, routine testing of patients on cognitive function tests for the statin group of drugs shows no problems as such.”

He goes on to state:

“This means that things that should be happening routinely that depend to some extent on muscle memory aren’t happening in the same way. This leads the person to have to concentrate harder than ever but despite this they still make mistakes and figure that clearly their memory isn’t as good as it should be. However at the same time cognitive function testing if undertaken is highly likely to come out as normal because the person’s brain is in fact normal.”

The solution? Professor Healy recommends to be physically and mentally active to refashion nerve endings.

“Activities such as walking or swimming may be helpful specifically if undertaken in a graded program that ensure there is daily activity and over time builds the activity levels up.” and ” To adopt, if possible, the same approach that people who have muscle memory problems for example take to playing the piano after an injury to an arm or hand – the advice is to get back playing if you can and evolve by sheer dint of practice another set of memories that will help make functioning smoother.”

Genetic Tolerance

Professor Healy’s “Guide to Stopping Anti-depressants” also states:

“A small number of people have a severe “toxic” reaction to SSRIs with neurological and other features often starting within days of starting treatment. The after-effects may endure for months or years. These drugs in the doses they are usually given are grossly overpowered. It’s like a huge articulated truck traveling down a stone-walled country lane.”

Whilst Professor Healy does not expand on this point, I want to make the point, that a simple life-long DNA Dose test can tell your bio-individual genetic response to anti-depressants. It is my personal believe that every individual prior to being given anti-depressants, due to its withdrawal legacy, should be given this test.

Professor Les Sheffield, from DNA Dose, concludes that only 50% of people have a normal response to anti-depressant medication, 40% of people need their dosage adjusted, and 10% of people are unable to metabolise medication. This means that it may not be the medication, so much as the dose, and the ability to detoxify or methylate it, that may be important for histamine intolerance.


Withdrawal syndrome from psychotropic medications is extremely complicated and should be done under medical supervision. As an aside, Professor Healy runs an e-clinc, where he consults on the prescription, and withdrawal of psychotropic medication.

My purpose in sharing this information is not to make recommendations in relation to anti-depressants but to cross-pollinate Professor Healy’s observations in relation to histamine intolerance.

In the context of my own healing from histamine intolerance Professor Healy’s observations appear extremely relevant.

I have had histamine intolerance all my life, but developed mast cell activation disorder, when put onCYP450 mediated (and in particular CYP2D6 related medication).

When I started this histamine intolerance healing journey my brain fog was so bad, that I could barely speak in a full sentence, could not read more than a paragraph, and could not remember basic information. That has gradually resolved by continuing to engage physically and mentally and not let my brain fog get the better of me. Reversal is slow but it is reversal. I will shortly write more about what has worked for me.

My histamine intolerance is now in remission. I have done this through diet and not medication.

There is a current theory, that mast-cell stabilisers, may in time reboot a hysterical, de-stabilised, histamine system. By standing down the histamine system, it stops hyper-responding, and histamine intolerance resolves. This theory is consistent with Professor Healy’s protocol. It is also my immunologist’s in relation to mast-cell activation disorder.

Personally, I tolerate so few medications, I have really had to use lifestyle medication, rather than prescription medication. Equally, for some of my clients, particularly those who tolerate so few foods to use food as medicine, mast-cell stabilisers have been their turning point. In the end this is a personal decision.

Additional Reading

Guide to Stopping Antidepressants by RxISK eCLINIC

Professor David Healy

DNA Dose

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  • Lara

    Wonderful article. When you mentioned that there is a current theory that mast-cell stabilizers may in time reboot a hysterical, de-stabilized, histamine system– do you mean medications like ketotifen? Are there any others I’m not aware of? So these may actually have a place in healing histamine intolerance/MCAS (if lifestyle medication isn’t enough) compared to chronic use of antihistamines that help create the problem? Thank you for writing this informative article. The tips were very helpful. This is exactly my story but I’m still in the grips of debilitating brain fog. I developed my symptoms while taking Effexor, an SNRI, for almost a year and after a round of antibiotics. Two years of massive doses of antihistamines were ineffective and only made me worse. I’m off all of that now and your story gives me hope for the future! I’ve been worried that my histamine system is messed up for good after these medications. I really enjoy your blog. Thanks again!

    • Hi Lara, thankyou for your kind comments, sadly you are not alone. Yes I do mean ketitofen, and also cromolyn sodium, is another alternative that Professor Healy mentions. I think that it is equally possible to reverse this through diet and lifestyle but some of my clients can eat so little foods (needed to do that) and get a massive jump in the number of foods through medication. Please also consider a DNA Dose test as if you have adverse effects to anti-histamines it could be linked to a genetic mutation.

      • Lara

        Thank you for the advice Alison. I really appreciate it!

      • Penny

        Hello Alison.
        I am one of those people that tolerates too few foods to manage symptoms with diet. I am taking ketitofen and have a script for cromolyn sodium, but it is so expensive here! What i am wondering is do you know people in Australia who are taking it, and if they have found an affordable source? My doctors don’t know of one.

        Best Wishes,

        • Hi Penny
          I assume you are in Australia? Is that right? Assuming it is then you can purchase CS with a script from a compounding chemist ( e.g. but it is expensive. However, you can also access CS via medicare but they need to obtain special authorisation. Also with ketitofen it can be imported with special authorisation from the TGA. Professor Pete Smith on the Gold Coast has done both so if your doctor is unsure how to do so and is obliging perhaps they could contact him at the QLD Allergy Unit and ask for help. CS is much better for food intolerances. Hope that helps.

          • Penny

            Hello Alison.
            Yep i am in Australia.
            Thanks for those suggestions, i will check them out 🙂

            X P.

          • Penny

            Hello again.

            Would you happen to know any medical practitioners in South Australia who know a lot about MCAD/MCAS? Everyone seems to mostly only know about mastocytosis.
            Or if there was someone in another state who is willing to do phone/skype consultations?

            Regards, Penny.

          • Sorry I dont know any medical practitioners in SA or who do skype consultations. Have you tried taking the papers in this link to your practitioner?

  • LeeAnn

    Alison, I am so glad I found your blog. It has put several missing pieces of the puzzle together for me. I developed HI after my Dr put me back on Tamoxifen (another Dr had taken me off because she didn’t think I was metabolizing it). After reading your post about the CYP SNP’s (I am hetero and homozygous for several) and certain medications I was able to confirm that the Tamoxifen did indeed trigger it (after numerous Drs told me absolutely no). What kind of Dr would diagnose a mast cell disorder, allergist? Immunologist?

    • HI Lee Ann I am also so glad you found my blog too! ADR are so easily missed because doctors simply are not trained in them and this area of medicine has changed so much in the last four years. Firstly, I really really recommend that you consider the DNA Dose test at You can get it done from anywhere in the world. The reason I say this is it will a) give you precise clarity as to what you can and cannot take, and at what dose, and b) it communicates it in a way that even the most uneducated doctor responds and you can jump to the end game. Once they understand that you have effectively been poisoned (as unable to metabolize the medication). It will mean that your medical condition is taken seriously. Then in terms of diagnosis the person you need will typically depend on where you are based but here in Australia it is an Immunologist. It is worth checking if they work in the area of histamine intolerance and/or mast-cell disorders first. Hope that helps!

      • LeeAnn

        I live in the US….. Will definitely look into that test. I have been scared to even see a Dr about this because I don’t want to be put on a medication that might make it worse. How long did it take you to go into remission? Do you work with clients on making dietary modifications? I felt like I had made so much progress but over the past few days I have been feeling like I did a few months ago. Always seems like 2 steps forward then three steps back!

        • HI Lee Ann – I know what you mean – doctors come from a medical model – but I also choose to often just treat them as scientists (ask them questions only!). The test made it easy for me to communicate my drug sensitivity to them – but they are really only trained in drugs. It took me about two years to put the whole thing into remission but that was also me fumbling around working this dang thing out. I had big jumps though throughout. I do work with clients – on not only diet, but a range of lifestyle modifications, that help. I also help guide clients through the medical system. You can book a free consultation via the “work with me” button above if you want to discuss generally how I can help.

  • Sharon

    This is such an interesting article, thank you so much. After 4 years, I recently successfully withdrew from both antidepressants and benzodiazepines prescribed for post partum depression (insomnia was my actual symptom). I could go into great detail about the vast over medication, and the ghastly 2 year miserable torturous withdrawal to get off of a relatively small dose of clonazapam, but most significant for this discussion is that the moment I was completely off the last pill, I started getting strong symptoms of histamine intolerance, something I had never had in my life. This, however, was confounded by a change in diet that I started in an attempt to speed my health and recovery ( I went on a paleo diet for autoimmune disease because I also have psoriasis). So… I withdrew from antihistamine-like drugs, I added higher histamine/higher protein diet (although my diet always was high protein) and I have a mast cell destabilizing autoimmune disease. Sounds like a perfect storm right? Except prior to the drugs, I had been on a paleo diet with high protein, ate fermented foods daily, still had the psoriasis, but never a problem. I ate very high histamine (but healthy) foods for years. So, to me, it was the drugs that really destabilized me. It started 3 months ago with dizziness, randomly, and severe brain fog 5 minutes after eating fermented foods. That severe and immediate reaction to fermented foods actually allowed me to very quickly determine the histamine connection. I tried antihistamines and they helped with the brain fog and dizziness by 50% at least, so that also confirmed it for me. But a month ago, I was still treating this rather like an acute and temporary condition (ie. not seriously enough), and I went out to a Chinese restaurant and ate a soup that was likely both very high in histamine and MSG. I got brain fog after that meal, and 40 days later, I continue to have debilitating levels of brain fog every day. I can literally spend hours of the day in a stupor, especially if I have to read on the computer. I wake up with it, it worsens after consuming any food, stays all afternoon, and only lets up usually at 9-10 pm. I hear that histamine is involved also in sleep wake cycles, and my brain fog in addition to connections to food, are very sleep wake related – bad in the morning when histamine is high, better in evening when histamine is low. I have gone on an extreme low histamine diet, obeying every rule. I am sensitive to just the digestion process even with low histamine foods right now. Only twice have I beed in the situation where I was forced to have a protein where it might have been left out for more than an hour cooked and I suffered extreme and immediate symptoms of diarrhea, dizziness, brain fog, stomach bloating and very bad headache. I have taken DAOsin and it takes my brain fog away within 20 minutes typically – in conjunction with a very low histamine, food intolerance free diet. I am now gluten, dairy, soy, nut, grain, sugar free. As well as a few other foods I have suddenly become intolerant to. I basically eat vegetables, fruits, and meat. I cannot give up meat, as I will have hypoglycaemia issues. I try to source carefully, consume immediately, and fast freeze any leftovers. My psoriasis has flared profoundly during this past month with these high histamine levels, and I am unable to lose weight I was successfully losing a month before (weight the pills made me gain). I refuse to take antihistamines because I get side effects, and am still debating about DAOsin as I worry that anything but totally natural recovery may be doing me harm by further unbalancing systems. I am truly frustrated and quite scared as there is no doctor in this world that I can trust with this – I have been harmed enough by pharmaceuticals and that is their go-to solution for everything – if I am even believed in the first place. I just don’t understand how I cannot eat foods I have eaten my entire life all of a sudden. It seems surreal. I have days that are better, and then I think I am finally getting better, but then for unknown reasons, I will have a bad spell, despite extremely strict adherence to diet. I just wish I knew 2 things, can I get better and how long will this take? And I’d love to know if DAOsin helps or harms recovery. I just wonder if I am supplementing DAO is my own body down-regulating DAO production because of a new external source of enzyme available. Hence harming in the long run. I suspect this is not a genetic deficiency of DAO in my case, as I have never had these symptoms before or issues with high histamine foods. Your articles have been so helpful in my pursuit of recovery.

    • Hi Sharon apologies for the delay in responding but this went into spam for reasons that I dont understand since your comment was so relevant! Firstly your response is totally normal for adverse drug reactions. Secondly DAO will not help as that is not the issue. What will help is certain mast-cell stabilising probiotics and I would seriously look at pyconogenol. I am going to shortly do a bit blog pose explaining the many faces of histamine intolerance. It will gt better believe me.

  • Sherry

    Hi Alison,
    I ran across your article and can’t comprehend due to brain fog.
    I battled indoor/outdoor allergies my whole life, taking over the counter to prescription antihistamines to getting 2 allergy shots weekly.
    Also, I was on Prozac for 20+ years and did fine but when I was put on Effexor for 1 year it wreaked havoc on my mind & body.
    NOW, I don’t have any allergies what so ever. NONE! My brain felt like a raisin and still does at times. I have extremely dry skin, scalp and my hair is dry and falling out. I’ve been trying to find a connection between Effexor and antihistamines. Do you think there is a connection and do you know of a test I can have done to confirm this? I would appreciate any help or guidance you can offer to me. Thank you in advance! Sherry

    • Hi Sherry not quite sure I understand what you are asking me. What precisely did you want to test for?

  • Chris

    Hi I was on 4mg of lorazepam which is a lot I’ve been off for two years and still have some really bad histamine issues. I’m trying to understand if your saying it will only get better if I take ketofin or will it get better if I just take nothing?

    • Hi Chris no ketitofen is not needed. I believe histamine issues can be caused by gut of liver issues. Testing around those issues can typically resolve histamine issues in my experience. I do hope that helps.

      • Chris

        Thank you for the response I do think your correct on the gut and liver can you tell me what type of testing needs to be done cause every dr seems clueless at this point mabe it would help them to know where to start

        • You would need to work with a functional medicine professional not a doctor. A doctor only works with illnesses and offers drugs and/or surgery as the options. A functional medicine professional works with restoring health and should know what to do.

  • Miren Hary