Metabolism an unappreciated factor in drug effectiveness

I was touched, and surprised, by your editorial of Friday, May 20, headlined ‘Trying to understand suicide/Figures show we need to do far more’. I was touched by your compassion and surprised by your mention of “variations in metabolism”.

Metabolism an unappreciated factor in drug effectiveness

Although gene tests can establish whether patients will tolerate or adversely react to drugs, these tests are not available in Ireland. It is especially psychiatrists who ignore the findings of reports on such drugs, thereby risking patient lives.

Since the introduction of psychiatric drugs, the rate of suicide in schizophrenia has risen 20-fold, according to Healy et al (2006), who compared rates from 1825-1924 to 1994-1999.

Nearly all psychiatric drugs are metabolised by the liver cytochrome enzyme, P450 2D6, but more than 20% of Europeans have a so-called polymorphism in this enzyme.

They become ill due to this deficiency, because many xenobiotics (pharmaceutical drugs and environmental toxins) are metabolised through this enzyme (Maréchal et al, 2008). That means they becomes ill because of the effects of environmental toxins (organophosphates, dioxins, mercury), but then psychiatrists add toxic insult to toxic injury and additionally burden a system that is underfunctioning. Often, drugs are administered by force, if patients refuse to take them because of unbearable side-effects.

I learned of two people who killed themselves because they were about to be treated involuntarily, after having already had a previous treatment in a psychiatric hospital.

Starting with my extreme sensitivity to chemicals, I found two underlying conditions that cause extreme reactions to chemicals. A substance called hexachlorbenzene (HCB) plunged me into despair and hopelessness. I had been in reasonably good health before. HCB is known to cause porphyria, a blood disease. In porphyria heme, the oxygen-carrying particle of haemoglobin is interfered with by the effects of chemicals. The other factor in chemical sensitivity is glucose-6-phosphate dehydrogenase deficiency, which may be a factor in schizophrenia. It is also a blood disease, causing too low levels in glutathione, an important anti-oxidant.

Mild forms of these two illnesses are the cause of chronic illness, be it physical or mental.

The Irish have relatively high levels of both porphyria and of G6PD. Viking ancestors may be the cause of the high rate of porphyria. Sweden and Norway have the highest rates in the world. The high rate of G6PD might be due to trade links with Spain, the origin of that genetic trait. G6DP gives a certain advantage in cases of malaria.

CYP 450 enzymes are heme enzymes. Heme plays a huge role in numerous biochemical processes. Tryptophane pyrrolase, the drug target of SSRI antidepressants, is a heme enzyme.

Especially, olanzapine (also metabolised via the CYP450 2D6 heme enzyme) can cause suicidal depression, after the drug is withdrawn. In the ‘wash-off’ phase, numerous patients have killed themselves.

Professor David Healy had access to the original data and found that, even in the drug trials, healthy volunteers killed themselves. Today, this anti-psychotic is prescribed for conditions such as insomnia, even to children. As far as I know, it still does not have a black-box warning.

Patients suffering from the effects, after withdrawal, may then be given SSRIs, thus aggravating the liver. Psychiatrists ignore the side-effects of the drugs they prescribe.

Coroners should not only find out which drugs had been taken, but also which drugs had been withdrawn, before a suicide.

A lot can be done to prevent suicide. Embracing environmental science and introducing gene tests would be the most important. So far, the life of a patient in psychiatry is not worth €1,000. That’s the amount such a test would cost.

Dorothee Krien

43A Ballydaheen


Co Cork

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