Pharmacogenetics: Ready for Psychiatric Practice?

International panel calls for a conservative approach on using genetic testing to evaluate, diagnose mental health conditions.
While it struggled to reach consensus on key issues, an expert panel that revised guidelines on psychiatry-related genetic tests recommended pharmacogenetic testing as a support tool in guiding clinical care decisions and stressed the importance of communicating incidental findings of genomewide testing in a clear and transparent manner.
More than 50 international experts from psychiatry, genetics, precision medicine, and other fields reviewed the latest scientific evidence on molecular genetic technologies, pharmacogenetics, and ethical issues to come up with eight recommendations on using genetics to diagnose and treat mental disorders. This represents the first thorough revision of the International Society of Psychiatric Genetics’ (ISPG) 2014 guidelines.
On their own, common genetic variants do not lead to depression, bipolar disorder, substance dependence, or schizophrenia, the expert panel determined. “Genotypes from large numbers of common variants can be combined to produce an overall genetic risk score, which can identify individuals at higher or lower risk, but at present it is not clear that this has clinical value,” the experts summarized.
The panel couldn’t agree on whether genetic tests should be used on a broad scale to help clinicians choose the best course of treatment for patients with mental illness. However, the group made some recommendations on pharmacogenetic tests. Pharmacogenetic-based drug therapies for psychiatric purposes at a minimum call for the availability of genetic information for the genes encoding enzymes CYP2D6 and CYP2C19 and genes HLA-A and HLA-B. When considering drugs such as carbamazepine and oxcarbazepine, the panel recommended that clinicians conduct HLA-A and HLA-Btesting to identify patients at risk for developing rare but serious side effects to these drugs.
“Evidence to support widespread use of other pharmacogenetic tests at this time is still inconclusive, but when pharmacogenetic testing results are already available, providers are encouraged to integrate this information into their medication selection and dosing decisions,” the panel indicated. Regarding CYP2D6 and CYP2C19 enzymes, such genetic information would provide the most benefit to patients who have had poor responses to a previous antidepressant or antipsychotic trial.
The panel also called for clarity and transparency in reporting incidental findings of genomewide testing. “Procedures for dealing with such findings should be made explicit and should be agreed with the patient or study participant in advance. The autonomy of competent individuals regarding preferences for notification of incidental findings should be respected,” it specified. The experts also recommended that professionals with mental health and genetic test expertise offer counseling to patients who undergo diagnostic or genomewide genetic testing.
Whether copy number variants, or CNV, testing should be widely used in adult-onset mental disorders was another topic of disagreement among the panelists. CNVs aren’t that common in adults, yet some experts believe that identifying certain CNVs in adults with severe conditions such as schizophrenia could assist patients and families in processing a diagnosis.
More education and research is needed to frame this debate and provide clarity on genetic testing’s role in psychiatric care, the panel determined.
The guidelines aim to help nonspecialist clinicians who face increasing requests for clinical genetic tests by patients and families but find it daunting to evaluate such tests. This is a “commitment to provide meaningful guidance to healthcare providers who urgently need it to treat their patients in the best possible ways,” ISPG President Thomas G. Schulze, MD, professor of psychiatry at the University of Munich, said in a statement. While clinicians should take advantage of the advancing field of psychiatric genetics, Schulze cautioned that “we should not succumb to overly optimistic claims.”