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 common drugs may help mental illness

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

https://www.ucl.ac.uk/news/2019/jan/widely-used-physical-health-drugs-may-help-treat-serious-mental-illness

The full paper

Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness

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.

The Swedish Disease

Ted, (aged 12, and supposedly “normal”) and his brother Monty (aged 9, and now steadily becoming more “normal”, as this blog progresses) go to the same school as a Swedish family.  In Ted’s class is a Swedish girl, Charlotte, and her younger brother is in the Primary school along with Monty.  I have been both surprised and impressed, by how nice the kids in Primary are to kids with any kind of special need.  However, once they make the big leap to Secondary, they stop being so nice; it becomes cool to be critical and even cruel.

Ted’s Swedish friend, Charlotte, was explaining to their class that her younger brother had something called Attention Deficit Hyperactivity Disorder, but it was OK, because he only had 10% ADHD.  Ted of course then replied “and you have got the other 90%”.  Some of the other things they get up to are far, far worse; one reason why I put Monty down a couple of years in Primary.

But, the Swedish Disease is not ADHD.

During my research, I recently came across some references to so-called “Somali autism clusters”; this caught my attention and so I decided to delve deeper.

It seems that following the descent of Somalia into becoming a failed state, many refugees have been welcomed by the United States and Sweden, in particular.  In the US there are now communities living in Minneapolis and San Diego.  Not long had they arrived in their new homeland, when they started to produce large numbers of autistic children; sounds odd does it not?

Swedish researchers got on the plane to Minneapolis in the US, to launch a joint investigation and it was reported that Dr Wakefield wanted to go to San Diego to investigate.  The Swedes did not come up with an explanation that convinces me.  I think I have a much better one, and one that Dr Paul Ashwood, from the University of California might agree with.

The Swedish Somalis said they had never encountered autism before and so they named it the “Swedish Disease”.  The Swedish researchers concluded that since both Sweden and Minneapolis are far north, where the sun does not shine so much, the autism was the result of a lack of vitamin D.  That sounded odd to me; what about the cluster in San Diego that Dr Wakefield wanted to get in touch with?  Last time I was in California, the sun hardly ever went away.

A much more likely explanation is related to the immune system.  I have never had the pleasure of touching down in Mogadishu (the capital of Somalia, in case you did not know) but I did travel extensively in some poorer parts of Asia.  The level of hygiene and cleanliness in rural parts of India would really shock most westerners; the most effective strategy is just not to eat anything.  I came back 9 pounds lighter.

In my recent posts, I showed how the immune system plays a major role in the predisposition of children to autism; to me it is hardly surprising that first generation Somali children, born in ultra-clean Sweden and America, have a high incidence of disease related to the immune system, and to neuroinflammation in particular.  I dare say they never had much asthma in Somalia either.

The parents’ immune system has been toughened by all manner of parasites, bacteria and virus and has no doubt evolved to be prepared for it.  The children inherited their parents’ immune system, but it has stopped being challenged by any kind of serious attack.  Then in utero, or in very early childhood, a big oxidative shock came along and the immune system went crazy and over-reacted (a cytokine storm); massive neuroinflammation caused permanent brain damage and autism was the result.

It’s just my theory, but if you ever read that Somali immigrants are complaining about asthma and food intolerance, it might just be right.

More recently, the Swedes did a very large study looking at autism in all their immigrant population, here is an interesting link discussing the study:- 

Swedish study dissects autism risk in immigrants