Harnessing genetics to reduce trial and error antidepressant prescribing

The world health organization estimates 350million people globally suffer major depression. The condition is one of the leading causes of disability globally, with the burden of disease from depression projected to grow in coming years. For many sufferers antidepressants are a necessary part of treatment. But months (sometimes years) of trial and error can pass before finding an effective tolerable antidepressant for a particular patient. There are over twenty different antidepressants available, and patients have differing responses to them. Some of this variability is due to our genetics.

A randomized controlled trial published in the latest edition of The Journal of Clinical Psychopharmacology and Neuroscience suggests antidepressant efficacy can be improved through a genetically guided prescribing (precision medicine) report.

The study compared genetically guided prescribing to traditional unguided prescribing. Genes involved in how people metabolise antidepressants in the liver and genes influencing how readily the medications cross into the brain (via the blood-brain-barrier) were used to generate a medication guidance report for use by the patient’s treating physician. The study was conducted in Victoria, Australia with 148 patients involved. Those receiving genetically guided treatment had double the symptom remission rate at the end of the twelve week study. They also had reduced side effects and less need to take sick leave due to their depression.

The lead author Dr Ajeet B Singh MD – an Australian Psychiatrist and Pharmacogeneticist – is cautiously optimistic about the finding: “This study is the first positive randomized controlled trial for genetically guided antidepressants. But independent replication by another research group will be needed to confirm the finding.” He adds: “I believe in years to come as the evidence builds, genetically guided prescribing will enter routine practice and help reduce trail and error.”

Dr Singh hopes to make the guidance report (called CNSDose) available to clinicians, but stressed that “Patient care needs to remain within the safeguards of the doctor-patient relationship, the evidence for this technology is still in the early phase. Such genetic reports are thus optional at present, and patients should discuss the merits of them with their own doctor.”

Over the past few years the cost of genetic testing has dramatically dropped – falling from thousands of dollars to under one hundred dollars for some tests. This cost reduction makes testing more affordable, enabling wide implementation if clinical benefits are confirmed.

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