The role of pharmacogenomic testing in psychiatry: Real world examples

To the Editor

Predicting the efficacy, side effects and optimal psychotropic dose for individual patients is a challenge in psychiatry. Current prescribing patterns follow the maxim ‘start low, go slow’. If patients are unresponsive or adverse effects occur, medication is changed. This is time consuming, inefficient and may lead to prolonged illness and financial strain. Patients may experience a sense of hopelessness, and there may be negative impacts on the therapeutic relationship.

Pharmacogenomics is the study of the impact of genes on drug therapy (Krasowski, 2011). Since the 1950s, pharmacogenomics has sought to optimize drug therapy by tailoring medications and doses to the patient’s genetic make-up. The following cases describe patients who underwent pharmacogenomic testing using GenesFX Health (Melbourne, Australia) following consultation at the Monash Alfred Psychiatry Research Centre (MAPrc) Women’s Mental Clinic.

A 35-year-old single woman, Ms A, was referred to our clinic for a second opinion on the management of ‘agitated depression’. Her depression began following a motorcar accident 8 years prior, after which Ms A experienced panic attacks, flashbacks and several impulsive suicide attempts. She had consulted multiple medical professionals and tried several antidepressants, but she experienced side effects even at small doses. Doctors labelled her as ‘somatizing’, citing her proclivity to side effects ‘abnormal illness behaviour’.

Pharmacogenomic testing confirmed that Ms A was highly sensitive to medications. Her results showed slow action of the cytochrome p450 enzyme encoded by the CYP2C19 gene, meaning she was a poor metabolizer of most antidepressants. Ms A was commenced on a small dose of venlafaxine (25 mg BD) and a low-dose short-acting atypical antipsychotic (quetiapine IR, 25 mg/day). Three months later Ms A was much improved.

The second case describes a 43-year-old woman, Ms B. She worked long hours as an administrator, living alone with poor social networks. She presented to her GP with a 6-month history of typical depressive symptoms and was prescribed an antidepressant, but did not improve after 4 months of treatment. Ms B’s pharmacogenomic profile showed increased function of enzymes encoded by CYP2D6 and CYP2C19 genes, meaning she was an ultrarapid metabolizer of most antidepressants. Following the result, Ms B was treated with escitalopram at 30 mg/day, higher than the recommended 20 mg/day. Two months later she felt much better.

Pharmacogenomic testing has the potential to aid clinical decision-making and avoid difficulties in usual prescribing practice. There is a need for prospective trials to confirm the economic and clinical benefits (Eichelbaum et al., 2006; Sheffield and Phillimore, 2009).