Levothyroxine Augmentation in Clozapine Resistant Schizophrenia: A Case Report and Review

Why should what is claimed to be someone with normal thyroid function improve when taking levothyroxine? And worsen when it is stopped? Is it the very definition of normal thyroid function they are using?

Case Rep Psychiatry. 2015;2015:678040. doi: 10.1155/2015/678040. Epub 2015 May 11.

Levothyroxine Augmentation in Clozapine Resistant Schizophrenia: A Case Report and Review.

Seddigh R1, Azarnik S2, Keshavarz-Akhlaghi AA1.

Author information

• 1Mental Health Research Center, Iran University of Medical Sciences, Tehran, Iran.

• 2Shahid Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.


There are many reports that show different thyroid abnormalities in schizophrenia without clear establishment of their role in etiology and treatment outcome of schizophrenia. Among these reports, there are only a few that consider a role for thyroid hormones as augmenting agents in the treatment with antipsychotic drugs. This case report outlines symptom subsidence of a patient with clozapine refractory paranoid schizophrenia and normal thyroid function who added levothyroxine to clozapine and found that symptoms of psychosis returned once levothyroxine was discontinued. Although this observation needs to be confirmed in controlled clinical trials, we aimed to discuss possible hypothesized mechanisms underlying this observation.

PMID: 26078905 [PubMed]


18 Replies

  • Helvella, low-normal 0.5-2? Or high-normal 5-10? If we know it makes a difference why don't the researchers?

  • Post an abstract and all I get is a pedant suggesting there is a difference between 0.5 and 5! :-) (Helvella has never had a TSH below range, and only the merest smidgin over-range at diagnosis. Yet Helvella feels a massive difference between the time of diagnosis and now - despite being older now.)

    Quite - and I can't decide if it is a good thing to see things are the same the world over - or not.

  • Helvella, Not good. I think it might help us in the UK if some of our Euro chums defined TSH normal as <3.0 or, radical thought, trialled symptomatic patients for up to 6 months on Levothyroxine with TSH (>1.5). If it helps symptoms the patient needs it, if it doesn't, discontinue it with no harm done.

  • It seems T3 can be more effective than antidepressants in people with Bipolar esp fast cycling (family clusterings of the two conditions - schizophrenia and bipolar - seems to point to a hereditary component) in one study of antidepressant resistant subject on an average of 90mcg T3 c70% had improvement and and c30% complete remission which is staggering, but no one knows why it works even in those with normal TSH (American limits) t4 is not as good and NDT has not really been researched. After 5 years those on those mega doses had zero signs of hyperthyroidism. It is fascinating. Will try and add some links for you. One was a huge study published on the U.S. Research site:

    STAR D

    Here's one:


    And another on T3 versus lithium for depression:


  • Promotes deep questions about the meaning of serum levels of both TSH and FT4and FT3.

    Yes - have seen T3 and depression and bipolar linked many times - but I don't remember a specific paper about schizophrenia and levothyroxine. I also feel very strongly that we tend to ignore papers simply because of the country they come from. I remember a USA citizen I met - seemed fine but as soon as you mentioned "Russia", she froze and told you never to even say the word again in her presence.

  • No me neither, but as the conditions appear to be different faces of the same coin (or that's what I think) it seems obvious to me what affects one would probably affect the other. I think Kelly has done a fair bit with T4 for bipolar.

  • Wretched site will not display correctly on my iPhone Clutter - infuriating as it looks interesting

  • TSH110, that's a shame. It's not one of those irritating sites with lots of pop ups which cause problems.

  • I will check it out on the computer I can read a bit but all the side bar headings are encroaching into the article txt.

  • So thyroid meds stopped psychosis, no less, in schizophrenics, but it never occurred to anyone doing the study that the poor sods might have a physical problem with thyroid? That beggars belief...

  • Come on Chancery, keep up at the back! It is obvious that having a TSH in range means there is no possibility of a thyroid problem. That is, after all, the effective definition of "normal thyroid function" in our times.

    [ For clarity, in case anyone were think that was serious, I declare full sarcasm mode. With a degree of bitter observation. ]

  • So you think they do have an undiagnosed thyroid disorder I guess it makes sense rather than some mysterious aspect of thyroid function they cannot fathom yet. I just accepted that it was not thyroid disorder...and after what I had to go through before getting a diagnosis....

  • Not meaning to be pedantic, but their thyroids may be perfectly well, even their control over their thyroids (pituitary and hypothalamus), and their blood may be fine. But if the actual cells, or at least some of them, do not transport thyroid hormone into their interiors, and if it does not have the required effect there, then I do think that thyroid might be behind this.

    For example, it has been pointed out that thyroid hormone has to be actively transported across the blood-brain barrier. If there is anything wrong with that process, might you not end up with the potential of having a body with enough thyroid hormone and a brain with not enough? Even, in the extreme, a hyper body and a hypo brain.

  • Dear God, Rod (ooh, a poem!), you'll be suggesting next that doctors actually take note of the patient's symptoms and what makes them better, and then did that (shudders), regardless of any blood tests.

    Don't you know that would be UNSCIENTIFIC?

    Really, I don't know what's wrong with you today.....

  • Thanks for the elucidation Rod which makes good sense to me. I feel much better on NDT than Levo probably for similar reasons. Do you think it could be genetic like the gene that affects T4 to T3 conversion?

  • Maybe their 'tests' are in range particularly TSH but the levo converts to sufficient T3 and the brain contains the most T3 receptor cells so it is really the liothyronine which is the 'magic' hormone for many and not levothyroxine .

  • I'm really sorry. I must have just dozed off for a moment or something. I don't know what came over me. I'm right back on it now. I promise.

    Having a TSH in range means there is no possibility of a thyroid problem.Having a TSH in range means there is no possibility of a thyroid problem.Having a TSH in range means there is no possibility of a thyroid problem.Having a TSH in range means there is no possibility of a thyroid problem.....

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