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The Important Role of Genomics and Pharmacogenetics to enhance Mental Health Treatment

Research into some mental health conditions has been aided by the incredible progress of genomics (the study of genes and their functions through genetic testing). Genomics has started to have a significant impact on many areas of clinical care including mental health management.

Take conditions such as anxiety disorder and chronic depression; when previously treating mental health issues like these, drug dosage was based on empirical (or observational) evidence.  With this type of approach, it is not always possible to predict a patient’s probability of response, the risk of side effects and the dosage needed for a drug to be effective. This means that patients did not often respond well to their prescribed treatment, or they experienced unpleasant side effects (that often lead to discontinuation of the medication).

Well-established studies of pharmacogenetics (how genes affect a patient’s response to drugs) have demonstrated that individuals have different ways to metabolise medications according to their genetic make-up.

Metabolism is aided by enzymes in the body. The most important cytochromes (enzymes in the body) with regards to metabolism and mental health conditions are CYP1C19 and CYP2D6. Many antidepressants often used in mental health treatment (including fluoxetine – Prozac and Sertraline) are metabolised by CYP2D6. Individuals that have this overactive cytochrome might need to adjust their medication dosage in order to be able to respond to treatment in the best possible way.

Which type of metaboliser are you?

Much of the population are defined as ‘normal’ or ‘extensive’ metabolisers, that is, they can metabolise a drug in a ‘normal’ way because the two genes that code for the molecules involved in drug metabolism –the cytochromes – are present and active in those individuals.

Other people are defined as ‘intermediate metabolisers’. They can metabolise a drug, but they do so in a less efficient way than ‘normal’ because only one required gene is active rather than two.

Then some individuals either metabolise drugs extremely rapidly (‘ultra-rapid metabolisers’), or, they don’t have the ability to metabolise some drugs at all (‘poor metabolisers’).

Ultra-rapid metabolisers often need a significantly higher dose of medication, or a different medication altogether (one that is not metabolised by the same molecule), as a standard dose of medication is not effective for them.

While poor metabolisers do not metabolise medication, which means that even standard doses of medication, might be toxic to them.

Different populations have diverse prevalence of ultra-rapid or poor metabolisers. People from the Middle East, for instance, have a significantly higher percentage of fast metabolisers compared to the Caucasian population.

This means that this population is most likely to need a genetic screening of the cytochromes compared to the Caucasian population.

How does metabolic data help?

Knowing the metabolic status of a patient is helpful – not just to optimise treatment – but also to avoid unnecessary side effects (which can be extremely severe). One drug where the importance of a patient’s metabolic status is frequently referenced is codeine. Once this drug has entered the system, it converts into morphine. Individuals who are ultra-rapid metabolisers will convert codeine into morphine at a phenomenal speed and therefore, even a dosage that is considered safe in the majority of population, can be toxic or even lethal to these types.

For this reason, the best health care providers have incorporated genetic testing into their routine clinical practice for patients with mental health conditions.  This type of personalised approach to patient research helps practitioners take a more individual stance when treating mental health concerns.

Dr Antonio Metastasio – Consultant Ps
DR ANTONIO METASTASIO
Consultant Psychiatrist

Dr Metastasio qualified from the University of Perugia (Italy) in 2000. He then trained as Geriatrician in Italy. Subsequently, he moved to the UK and completed his postgraduate training in Adult Psychiatry (with an endorsement in Addiction and in Rehabilitation Psychiatry) at Cambridge in 2012. Dr Metastasio also completed his MSc in Addiction Biology at the Institute of Psychiatry, King’s College London in 2012. He was appointed Consultant Psychiatrist the same year.

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