Neuroleptic Awareness
Introduction > Pharmacogenetics

Pharmacogenetics

Pharmacogenetics determines each person's functional ability to metabolise and excrete prescribed drugs; the efficacy of medication is determined by natural human genetic variations which influence peoples response to medication.

Psychotropic drugs are metabolised through various sites and systems in the body. One major site is the CYP 450 Cytochrome family, which are found primarily in the liver.

75% of all psychotropic drugs are metabolised through the CYP2D6 and 15% through the CYPC19 pathway.

Pharmacogenetics has been known and used by pharmaceutical companies for many years. Drug trials are conducted on people who are specifically selected for their efficiency for metabolising each specific drug. This enables pharmaceutical companies to show the best possible outcome for the new drug; this has the potential for minimising adverse reactions and side effects.

Adverse reactions and side effects are exhibited by people who have the genetic inability to metabolise the drug efficiently.

Genotyping is a blood test or buccal swab test for the CYP Family and can determine a persons ability to metabolise a drug. Different neuroleptic drugs are metabolised through different pathways.

For each pathway, persons are classified into one of four groups.

Poor Metabolisers (PM)
Intermediate Metaboliser (IM)
Extensive Metaboliser (EM)
Ultra Extensive Metaboliser (UM)

Poor Metabolisers (PM)
When a person depicts little or no enzyme activity for the cytochrome pathway, a neuroleptic drug normally metabolised through this pathway would reach higher concentrations in the blood stream and take longer to clear. The toxicities of chemicals escalate in the body, resulting in increased risk of drug induced side effects, drug elimination or lack of therapeutic effect. The recommendation for PM is that patients need to avoid drugs which require that specific pathway.

Intermediate Metaboliser (IM)
IM require a lower than average dose for optimal therapeutic response. The recommendation is to start at the lowest efficacious dose and avoid multi drug therapy that inhibits the same pathway.

Extensive Metaboliser (EM)
EM require the recommended dose as their efficiency rates are normal.

Ultra Extensive Metaboliser (UM)
May require an increased doses because if the higher rate of metabolism.

Persons vary tremendously with their genetic functioning.  7-14% Caucasians are Poor Metabolisers and 75% of all psychotrophic drugs metabolised through CYP2D6. Further information on the genetic efficacy for ethnic groups, together with more extensive details on genetic testing can be found in www.healthanddna.com     www.dxsgenotyping.com 

Persons who are PM and IM will experience an increase of iatrogenic conditions resulting in both physical and psychological deterioration previously described.   

The wider picture and implications are many.

In my experience many clinicians within mental health are naive about the genetic inability to metabolise psychotropic drugs and therefore many patients have the potential of being misdiagnosed.  For example a person who poorly metabolises the SSRI Prozac drug, has the potential for exhibiting manic psychotic symptoms and will be undoubtedly interpreted by many psychiatrists as ’schizophrenic’. Many professionals have the potential of unwittingly perpetuating patients’ suffering, resulting from psychotropic iatrogenic conditions. The legally sectioned patients are incredibly vulnerable, as they have no choice about taking neuroleptic drugs.

I think there is a professional requirement for each patient to be given the genotyping test prior to prescriber's' writing psychotropic prescriptions; I consider this precautionary measure would show professional responsibility in safe guarding patients from acquiring potentially dangerous toxic levels whilst within their care.

Many clinicians have abdicated responsibility for patients’ medication, stating this is the sole responsibility of the prescriber. I disagree. The impact of psychotropic drugs on patients’ affects the effectiveness of each clinicians' expertise and I perceive each team member equally responsible of the patients psychological and physical well being. Since many professionals work in multidisciplinary teams, each team member is equally responsible in working collaboratively together and needs to be aware of genotyping with its potential detrimental implications for patients. ‘Medicines management is everyone’s business’ NWW

In the NHS genotyping is available within general medicine to patients to assess efficacy for drugs, for disease such as Rheumatoid Arthritis, HIV, cancer and Crohn’s disease.  There is no patient charge for this genotyping test.

The NICE Guidelines have taken the decision not to include the genotyping test into Mental Health. In my opinion this decision is not in the interests of patients. Additionally NICE have left patients and their carers without a fully informed choice about taking psychotropic drugs.

However the test can be purchased for about £500 (depending on the number of pathways investigated) by patients and carers through Genelex USA. www.genelex.com Gelelx does not require a doctors  reference and the results are sent direclty to the customer.

In addition to the inner psychological torment and the downward physical spiral when patients are PM, many patients are trapped, locked up for their remaining life span in secure hospitals. Considering the NHS cost of maintaining persons with mental health difficulties, the inability to metabolise efficiently needs to be addressed; long-term maintenance in the mental health system is not cost effective. 

When pharmacogenetics come to the forefront of Mental Health, conflicts of interests may arise, which need to be taken into account, bearing in mind Mental Health practitioners are in their chosen professional to be of service to their patients who are primarily the consumers.

The denial of leading mental health clinicians in implementing the genotyping test for those people who are clearly suffering from inappropriate neuroleptic medication I think is unethical and immoral. One psychiatrist described Clozapine the 'golden wonder drug'; I thought more like  'golden poison'. An emotive word to use but the reality is that antipsychotics are neurotoxic and to perpetuate neurotoxicites ad infinitum within vulnerable people, particularly for those who are unable to metabolise antipsychotics, is inhuman.  

Useful websites and papers


Clarke C.,  Psychotropic Medications :  Remedies or Poisons? The Evidence from Pharmacogenetics   Asylum Magazine Summer 2010 Volume 17 Number 2

Clarke C.,  Side Effects & Psychopharmacogenetics : Policy-Makers Keep Dodging the Issue Asylum Magazine Autumn 2010 Volume 17 Number 3 

Bray J.,  Clarke C., Brennan G., Muncey T. (2008) 'Should we pushing meds'? The implication of pharmacogenomics  Journal of Psychiatric and Mental Health Nursing Vol.15 No.5 p.357-364     


Super CYP Database: A comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Preissner S., Kroll K., Dunkel M., Goldsobel G., Kuzmann D., Senger S., Günther S., Winnenburg R., Schroeder M. and Preissner R.
Nucleic Acids Res 38(Database issue): D237-43. (2010)
http://bioinformatics.charite.de/supercyp/ 

 

Psychotropic Medication and Cytochromes,  Pharmacological Iatrogenesis, Dr. Yolande Lucire
http://www.lucire.com.au/documents/Cytochromes-paradigmatic.aspx

 

Includes metaboliser type graph
http://www.prozactruth.com/drtphysician.htm 


Cytochrome P450 Enzymes and Psychopharmacology Sheldon H. Preskorn, M.D. and Anne T. Harvey, Ph.D.
http://www.acnp.org/g4/GN401000086/CH085.html

 

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