Pharmacogenetics

Pharmacogenetics determines each person's inherent functional ability to absorb or metabolise and excrete the toxicites from drugs; the efficacy of medication is determined by in born 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 CYP450 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 and has the potential for under reporting of adverse reactions and side effects.

Adverse reactions/side effects are exhibited by people who have the genetic inability to metabolise the drug efficiently, resulting in drug toxicities.

Genotyping is a blood test or buccal swab test for the various metabolising systems and can determine a persons ability to metabolise a drug. Neuroleptic drugs are metabolised through different CYP pathways; other systems are via dopamine and serotonin receptors and the polymorphic area of the serotonin gene transporter.

For each CYP450 pathway, persons are classified into one of four groups.

Poor Metabolisers (PM)
Persons have little or no enzyme metabolising activity. Consequently drugs reach high concentrations of toxicities in the blood stream as they take longer to clear from the body, resulting in drug induced side effects due to decreased drug elimination. The recommendation for PM is that patients need to avoid drugs which require that specific pathway. Drugs prescibed to PMs are not therapeutic.  

Intermediate Metaboliser (IM)
With IMs, side effects take longer to appear due to the slower build up of drug concentrations and may take upto two weeks.  Drugs prescibed to IMs are not therapeutic.  

Extensive Metaboliser (EM)
EMs have no side effects and the standard dose is therapeutic.

Ultra Extensive Metaboliser (UM)
UMs are ultra quick metabolisers and the standard dose is not therapeutic. UMs may require an increased dose because of the higher rate of metabolism. BUT in the case of prodrug use, drug toxicities raidly occur.

Persons vary tremendously with their genetic functioning.    40-50% African-Americans, 50% Africans and 26% Caucasians are ineffectual metabolisers for CYP450 2D6. The BME higher frequency of inefficient metabolisers, supplies a plausible explanation for over representation in PICUs and Low Secure Units.

Further information on the genetic efficacy for ethnic groups, together with more extensive details on genetic testing: http://genelex.com 

Persons prescibed antidepressants and who are PMs, IMs and UMs for prodrugs will experience an increase of neurotoxic behavioural conditions such as akathisia, insomnia, mania, delusions, hallucinations, serotonin syndrome, psychosis, suicide and suicidality and homicide and homicide ideation. 

These psychiatric drug induced conditions are toxic and need to be recognised as such as stipulated by the DSM IV and are NOT to be confused with functional conditions. However when the above psychological conditions are functional, if patients are inefficient metabolisers and treated with psychiatric drugs, thier mental health will deteriorate.    

The wider picture and implications are many.

The vast majority of 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, 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 psychiatric iatrogenic conditions. The legally sectioned patients are incredibly vulnerable, as they are not genotyped to ascertain their metabolsing status and have no choice about taking any psychiatric 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 psychaitric drug toxic levels within their care.

Many halth care professionals 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; 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 Pamphlet) and that includes all health and social care practitioners.   IAPT stipulates psychologists need to have a 'working knowledge' of medications particularly antidepressants.  

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.  The abssence of genotyping in mental health pratice is tantamoumt to discrimination.

The NICE Guidelines have been aware of pharmacogenetics since 2006, when I introduced the issue at a NWW pharmacy meeting. Subsequently the material provided at the time was archived because of potential added costs to treatment care. A one of £30 genotype test is minimal compared with the life long costs of inpatient care, police, ambulance and social services.

"Not in my remit" says CQC, NICE, BMA, GMC   

Meanwhile neither patients, doctors and carers are left without a fully informed choice about taking psychiatric drugs. The true facts arer being withheld.

Genotyping test can be purchased by patients and carers through Genelex USA. www.genelex.com Gelelx does not require a doctors  reference and the results are sent directly to the customer.

Patients who are unfortunate to be inefficient metabolisers are prescribed concomitant psychiatric drugs which further increases  thier psychological distres and is detrimental to thier physical wellbeing.  

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. 

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, cause early death and to perpetuate neurotoxicites ad infinitum when people are inefficient metabolisers, is a UK disgrace.  

This needs to change.

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• Putting Pharmacogenetics into Practice
• Metaboliser type graph