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Thursday 24 January 2019

Cheap common drugs may help mental illness










Stockholm, Sweden

When most people think of Sweden, they probably think of Volvo cars, now actually Chinese, and Ikea.  Today you will have to add keeping detailed centralized medical records to the list.
Today’s study included 142,691 individuals from the entire population of Sweden with a diagnosis of bipolar disorder (BPD), schizophrenia (SCZ), or nonaffective psychosis (NAP) who were 15 years or older and who were treated with psychiatric medication from October 1, 2005, through December 31, 2016. 
It is relevant to readers of this blog because it shows that some of the same cheap generic drugs written about in this blog to modify aspects of autistic brain function do indeed show up as beneficial to those Swedes, with BPP, SCZ or NAP, who had by chance been prescribed those drugs for other reasons.
Numerous genetic studies have shown that the genes miss-expressed in autism overlap with those miss-expressed in bipolar (BPD) and schizophrenia (SCZ).
Clearly some people will get upset about autism (AUT) being called a mental illness. Whatever you choose to call SCZ and BPD you really need to apply to AUT, they are clearly just 3 overlapping clusters of gene miss-expression.
The study was summed up nicely in this BBC article.


Cheap and widely used drugs for diabetes and heart health have potential for treating severe mental illness, a study hints.
It showed the number of times patients needed hospital treatment fell by up to a fifth when they took the drugs.
The researchers at University College London say their findings have "enormous potential".
But they, and independent experts, say the results now need to be tested in clinical trials.
The starting point for the researchers was a list of currently prescribed medications that science predicts could also help patients with severe mental health disorders.
The team focused on:
§  anti-cholesterol drugs called statins - which may calm inflammation linked to mental health problems or help the body absorb anti-psychotic medications
§  blood pressure drugs - which may alter the calcium signalling in the brain that has been linked to bipolar disorder and schizophrenia
§  type 2 diabetes drug metformin - which may alter mood
But rather than test them in trials, the scientists went looking for evidence in the real world.
   
The press release from the lead author, who is at University College London



The full paper



Key Points

Question  Are drugs in common use for physical health problems (hydroxylmethyl glutaryl coenzyme A reductase inhibitors, L-type calcium channel antagonists, and biguanides) associated with reduced rates of psychiatric hospitalization and self-harm in individuals with serious mental illness?
Findings  In this series of within-individual cohort studies of 142 691 patients with bipolar disorder, schizophrenia, or nonaffective psychosis, exposure to any of the study drugs was associated with reduced rates of psychiatric hospitalizaiton compared with unexposed periods. Self-harm was reduced in patients with bipolar disorder and schizophrenia during exposure to all study drugs and in patients with nonaffective psychosis taking L-type calcium channel antagonists.
Meaning  Hydroxylmethyl glutaryl coenzyme A reductase inhibitors, L-type calcium channel antagonists, and biguanides hold potential as repurposed agents in serious mental illness, and the central nervous system mechanism of action of these drugs requires further investigation.
Abstract 
Importance  Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI).
Objective  To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced psychiatric hospitalization and self-harm in individuals with SMI.
Design, Setting, and Participants  These within-individual cohort studies of patients with SMI compared rates of psychiatric hospitalization and self-harm during periods of exposure and nonexposure to the study drugs, with adjusting for a number of time-varying covariates. Participants included 142 691 individuals from the entire population of Sweden with a diagnosis of bipolar disorder (BPD), schizophrenia, or nonaffective psychosis (NAP) who were 15 years or older and who were treated with psychiatric medication from October 1, 2005, through December 31, 2016. Data were analyzed from April 1 through August 31, 2018.
Interventions  Treatment with HMG-CoA RIs, LTCC antagonists, or biguanides.
Main Outcomes and Measures  Psychiatric hospitalizations and self-harm admissions.
Results  Among the 142 691 eligible participants, the HMG-CoA RI exposure periods were associated with reduced rates of psychiatric hospitalization in BPD (adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.89; P < .001), schizophrenia (aHR, 0.75; 95% CI, 0.71-0.79; P < .001), and NAP (aHR, 0.80; 95% CI, 0.75-0.85; P < .001) and reduced self-harm rates in BPD (aHR, 0.76; 95% CI, 0.66-0.86; P < .001) and schizophrenia (aHR, 0.58; 95% CI, 0.45-0.74; P < .001). Exposure to LTCC antagonists was associated with reduced rates of psychiatric hospitalization and self-harm in subgroups with BPD (aHRs, 0.92 [95% CI, 0.88-0.96; P < .001] and 0.81 [95% CI, 0.68-0.95; P = .01], respectively), schizophrenia (aHRs, 0.80 [95% CI, 0.74-0.85; P < .001] and 0.30 [95% CI, 0.18-0.48; P < .001], respectively), and NAP (aHRs, 0.89 [95% CI, 0.83-0.96; P = .002] and 0.56 [95% CI, 0.42-0.74; P < .001], respectively). During biguanide exposure, psychiatric hospitalization rates were reduced in subgroups with BPD (aHR, 0.80; 95% CI, 0.77-0.84; P < .001), schizophrenia (aHR, 0.73; 95% CI, 0.69-0.77; P < .001), and NAP (aHR, 0.85; 95% CI, 0.79-0.92; P < .001), and self-harm was reduced in BPD (aHR, 0.73; 95% CI, 0.62-0.84; P < .001) and schizophrenia (aHR, 0.64; 95% CI, 0.48-0.85; P < .001.
Conclusions and Relevance  This study provides additional evidence that exposure to HMG-CoA RIs, LTCC antagonists, and biguanides might lead to improved outcomes for individuals with SMI. Given the well-known adverse event profiles of these agents, they should be further investigated as repurposed agents for psychiatric symptoms.

Conclusion
If you are trying to convince your GP to prescribe some drugs off-label for autism, this study may help you convince him/her.
If your spouse, or other family members, think treating autism is folly, they might also benefit from reading about this study. 

The very old drug Metformin, used to treat type 2 diabetes has been mentioned many times in this blog and in today's study it was suggested to alter mood.  For severe autism mood is often not such a big issue, but for some mild autism mood is the big issue.
This study again shows how Scandinavian medicine collects a great deal of very usable data, in a recent post we saw something similar from Denmark. This is an example of socialized medicine at its best. I suppose the English lead author could not gather equivalent data in his home country.






9 comments:

  1. Have you check vitamin d levels? It seems there is few among many people and could generate mental illnesses.

    Could happen also with iron.

    ReplyDelete
    Replies
    1. There is a lot written about vitamin D and autism. In some countries where it is not added to basic foods, there is widespread vitamin D deficiency, Egypt is one example.

      All kinds of vitamin and mineral deficiencies are possible and may have neurological effects.

      Delete
    2. So why don't you check vitamin D levels on your kid and give him some? Or you already did it and was OK?

      I know we can be afraid about the calcium, I read your theory. But still, could be a good thing to try.

      I also think Iron could have something to do, as I think that low levels can cause hyperactivity.

      Regards

      Delete
  2. Hello Peter and Community,

    Hope everyone is well (and staying warm!)

    I saw a very interesting story today I wanted to share on RNA editing and Autism, which I have linked as follows:

    http://newsroom.ucla.edu/releases/ucla-led-team-uncovers-critical-new-clues-about-what-goes-awry-in-brains-of-people-with-autism

    For those of you interested in reading more of the science, I was able to find the relevant paper on Biorxiv at:

    https://www.biorxiv.org/content/biorxiv/early/2018/10/17/446625.full.pdf

    It's a fascinating read, and hopefully it's yet another step towards better understanding the affected pathways in at least some cases of ASD (and therefore one step closer to therapeutics).

    Also, I've been busy over the last few months working on a very exciting project, that I'm hoping to be able to announce in the coming weeks. I think the community will be excited about this project. Stay tuned...

    AJ







    ReplyDelete
  3. Peter, do you know about artemisinin used as antimalarial drug? It also has antiinflammatory and immunosupressive properties.It is being used in autoimmune conditions. Cáncer, MS, RA, Autism why not?
    Valentina

    ReplyDelete
  4. Valentina, Artemisinin is yet another interesting ant-parasite drug that is being repurposed for other conditions. Since it has been used for 2000 years in China its safety profile is established.

    Much is unclear about its mode of action. It appears to be effective in cancer because it creates oxidative stress. Oxidative stress may increase the chance of developing cancer, but once cancer is established oxidative stress becomes a good thing, because cancer cells are very vulnerable to oxidative stress.

    Artemisinin can shift the immune responses from Th1 to Th2. This means it may be beneficial in many auto immune diseases, including autism.

    I think you would expect Artemisinin to have an effect in someone with autism. Whether it is a good effect depends on the specific person, but in a person with other auto-immune conditions the odds might well improve.

    Both the herb and the drug are available, I think the drug is more likely to be effective and have less side effects.

    ReplyDelete
    Replies
    1. Valentina, there have been a series of trials using Artemisinin in schizophrenia and recent studies like the one below that relate to GABAa receptors.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5236063/

      It does look interesting.

      Delete
    2. Peter, it is easier to get the herb, but the oxidative stress effect would be a problem here?
      Valentina

      Delete
    3. Valentina, there have been several trials in schizophrenia and oxidative stress did not seem to cause them to fail. You could just use the herb at the dose they used in the phase 3 schizophrenia trials.

      https://clinicaltrials.gov/ct2/show/NCT01391403

      Delete

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