Pharmacogenomics and Antidepressants UK



Pharmacogenomics (often refered to as drug-gene testing) is the study of a person's genes and how they relate to the efficacy of drugs, antidepressants are drugs which are used to treat depressive symptoms. According to the National Mental Health Morbidity Survey In the UK conducted in 2015, one adult in six has a common mental disorder (CMD): about one woman in five and one man in eight. Since 2000, overall rates of CMD in England steadily increased in women and remained largely stable in men. 50% of people taking first line antidepressants do not respond to them1 and 55% have bothersome adverse reactions2. Antidepressant Pharmacogenetic decision support tools can be used by clinicians to find out what works and actually give the patient something that they know will work, without the trial and error. Often antidepressant prescribing is performed on a first line, second line basis. For instance, in the UK, the British National Formulary recommends specific first-line antidepressant in accordance with the patients individual reported requirements3 including:

  • presence of concomitant disease
  • existing therapy
  • suicide risk
  • previous response to antidepressant therapy

For second-line therapy, i.e. when the 50% of the first drugs do not work the following strategies are often be considered:

  • increasing the dose of the antidepressant
  • switching to a different antidepressant
  • augmenting the treatment regimen with a non antidepressant agent
  • combining the original antidepressant with a second antidepressant

As pharmacogenetics become more vogue with pharmaceutical firms, more evidence is being produced on the subject. A quick scan of the most robust data produced so far indicates that genetic factors play a critical role (42–50%) in determining the differences in both response to and adverse effects of antidepressants [4, 5]. Currently applying these pharmacogentic techniques to everyday healthcare is cost prohibitive, however seeing that DNA analysis cost has fallen by a factor of over a thousand through this decade alone, shows that pharmacogenomics may become commonplace. So far, guidelines exist to assist clinicians in the use of genetic information for drug selection and/or dosing for the tricyclic antidepressants, carbamazepine, and phenytoin6. Most importantly the number one prescribed antidepressant, the SSRIs, can now be tested to see if the may have clinical value for a patient by looking at ethnicity and the serotonin transporter gene (5-HTTLPR, rs4795541)7. From a wider perspective, there are over 100 mediciations labelled by the United States Food and Drug Administration (FDA)8 with labels applicable to pharmacogenomic biomarkers.

1 Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry. 2009;70 Suppl 6:16–25, accessed 14th July 2018.

Papakostas GI. Tolerability of modern antidepressants. J Clin Psychiatry. 2008;69(Suppl E1):8–13, accessed 14th July 2018.

3 BNF NICE Antidepressant Drugs, accessed 14th July 2018.

4Tansey KE, Guipponi M, Hu X, Domenici E, Lewis G, Malafosse A, Wendland JR, Lewis CM, McGuffin P, Uher R. Contribution of common genetic variants to antidepressant response. Biol Psychiatry. 2013;73(7):679–82, accessed 14th July 2018.

5Crisafulli C, Fabbri C, Porcelli S, Drago A, Spina E, De Ronchi D, Serretti A. Pharmacogenetics of antidepressants. Front Pharmacol. 2011;2:6, accessed 14th July 2018.

6Pharmacogenomic Testing for Neuropsychiatric Drugs: Current Status of Drug Labeling, Guidelines for Using Genetic Information, and Test Options.

7 "Using Pharmacogenomics to Aid Antidepressant Prescribing", Psyciatryadvisor.com, published 26th January 2015, accessed 14th July 2018.

8 FDA. Table of Pharmacogenomic Biomarkers in Drug Labels. 2013 Mar; http://wwwfdagov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378htm

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