By Marvin Ross

One of the frustrations faced by those with schizophrenia, their families and their doctors is medication side effects. It can result in considerable frustration and in failure to achieve stability. In fact, patients will abandon treatment as a result. However, a group of researchers at McGill University in Montreal have suggested how this can be overcome through pharmacogenetics in a new research article just published in the Journal of Psychiatry and Neuroscience .

Drugs are metabolized in the body via the cytochrome P450 (CYP) super family of enzymes. These are the major enzymes involved in about 75% of drug metabolism. There are a number of CYP enzymes that work on different drugs and often a number that metabolize just one drug. Some drugs increase or decrease the activity of the the CYP and can be a major source of drug side effects. If one drug inhibits the metabolism of another drug, that second drug will accumulate in the body and thus require a lower dose. Or, the opposite can occur and the metabolism is sped up and the drug gets out of the system too rapidly to have much therapeutic impact.

Other substances can also impact the metabolism of drugs and cause problems. Probably the best known that caused a stir a few years ago with Florida citrus farmers is grapefruit juice. It can interferes with the metabolism of the statin drugs used to reduce cholesterol so doctors when prescribing those drugs will tell their patients to avoid grapefruit juice. Another interaction is between St John’s Wort used for depression and birth control pills. There are probably a lot of kids around who should have been named St John’s Wort because they were conceived when that drug nullified the birth control pills their mothers took.

If you have a family member on anti-psychotics, you’ve probably heard that if the ill person increases or decreases smoking to tell the doctor because his/her dose may need to be adjusted. That is because smoking induces CYP1A2 which is involved with the metabolism of clozapine, olanzapine and fluvoxamine.

The journal article discusses the case of a 21 year old with first episode psychosis who was initially placed on 10 mg of aripiprazole for 4 days. He developed disabling extrapyramidal rigidity. Risperidone at 2 mg caused hypersalivation and disabling daytime tiredness. The patient refused clozapine and olanzapine due to concerns about weight gain but agreed to try haldol. That resulted in tremors, stiffness and anhedonia.

Doctors then performed a CYP450 assay and found that the patient was a poor metabolizer for CYP2D6. The three drugs that were tried are likely too slowly degraded in people who are too poorly metabolized by this enzyme leading to the side effects observed. The patient agreed to try paliparidone as it is less metabolized by CYP450 as is also the case with amisulpride. It worked and the patient is now doing well.

Metabolism status is something that is rarely considered by most prescribers although there are now a number of commercial tests available to them. If this were done on a more regular basis, the prevalence of adverse events would be significantly reduced and patients would receive faster and better results.

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