What is the evidence for genetic testing in psychiatry?

From the Guidelines

Genetic testing in psychiatry, specifically pharmacogenetic testing, has a established clinical utility in guiding medication selection and dosing, and should be considered in cases of treatment resistance or multiple medication failures. This is based on the evidence from the study published in Mayo Clinic Proceedings in 2016 1, which provides pharmacokinetic pharmacogenetic prescribing guidelines for antidepressants. The study highlights the importance of genetic variation, particularly in the CYP2D6 and CYP2C19 genes, in determining the metabolism of certain psychiatric medications.

Key points to consider when using genetic testing in psychiatry include:

• Testing for CYP2D6 and CYP2C19 genetic variants can help predict how patients metabolize certain antidepressants, such as SSRIs, and guide medication selection and dosing.
• Patients with CYP2D6 poor metabolizer status may require lower doses of certain antidepressants to avoid side effects, while ultrarapid metabolizers might need higher doses for therapeutic effect.
• The evidence for genetic testing in psychiatry is limited to pharmacogenetic testing, and testing for specific genetic variants associated with psychiatric disorders remains primarily investigational.
• Genetic testing should complement, rather than replace, comprehensive clinical assessment.

The study published in Genetics in Medicine in 2007 1 also highlights the need for further research on the clinical utility of genetic testing in psychiatry, including the need for prospective studies on the relationship between genotype and clinical response, and the potential value of using CYP450 testing to manage patients with a history of poor response to SSRIs or other antidepressant drugs. However, the more recent study published in Mayo Clinic Proceedings in 2016 1 provides more up-to-date and relevant evidence on the clinical utility of genetic testing in psychiatry.

In terms of morbidity, mortality, and quality of life, the use of pharmacogenetic testing in psychiatry has the potential to reduce adverse effects and improve treatment response, leading to better patient outcomes. This is particularly important in cases of treatment resistance or multiple medication failures, where pharmacogenetic testing can help guide medication selection and dosing, and improve patient quality of life.

From the FDA Drug Label

Greater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, compared to about 10% in Taiwan and 4% in North China. South Asians, including Indians, appear to have intermediate prevalence of HLA-B1502, averaging 2% to 4%, but higher in some groups. HLA-B1502 is present in less than 1% of the population in Japan and Korea. HLA-B1502 is largely absent in individuals not of Asian origin (e. g., Caucasians, African-Americans, Hispanics, and Native Americans). Prior to initiating carbamazepine therapy, testing for HLA-B1502 should be performed in patients with ancestry in populations in which HLA-B1502 may be present Retrospective case-control studies in patients of European, Korean, and Japanese ancestry have found a moderate association between the risk of developing hypersensitivity reactions and the presence of HLA-A3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine

Evidence of genetic testing in psychiatry is present in the context of carbamazepine treatment.

• Genetic testing for HLA-B1502 and HLA-A3101 is recommended before initiating carbamazepine therapy in patients with ancestry in populations where these alleles may be present 2 2.
• The presence of HLA-B*1502 is strongly associated with the risk of developing Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients of Chinese ancestry.
• HLA-A*3101 is associated with a moderate risk of developing hypersensitivity reactions in patients of European, Korean, and Japanese ancestry.

From the Research

Genetic Testing in Psychiatry

• Genetic testing in psychiatry has become a topic of interest in recent years, with technological advances leading to the identification of numerous genetic variations associated with psychiatric symptoms 3.
• Establishing a genetic cause may provide patients and family members with an explanation for their problems and allow for targeted treatment of psychiatric and somatic comorbidity 3.
• Patients with psychiatric disorders are rarely referred for genetic testing, but guidelines suggest that patients with intellectual disability should always be referred to a clinical geneticist, and genetic testing should be considered in patients with other psychiatric disorders if there are "red flags" such as a positive family history or congenital abnormalities 3.

Indications for Genetic Testing

• Psychiatrists should consider genetic testing in patients with psychiatric disorders if there are "red flags" such as a positive family history, congenital abnormalities, developmental delay, dysmorphic features, movement disorders, or cognitive decline 3.
• Genetic testing may be useful in patients with psychiatric disorders who also have somatic symptomatology, as psychiatric disorders may be underpinned by a genetic anomaly 3.
• The prerequisites for predictive and diagnostic genetic tests, such as clinical validity and utility, should be considered when evaluating the use of genetic testing in psychiatry 4.

Patient and Healthcare Worker Perspectives

• Healthcare workers and patients have varying perspectives on the use of genetic testing in psychiatry, with some viewing it positively and others expressing concerns about organizational, ethical, and legal implications 5.
• Patients' perspectives on genetic testing in psychiatry vary, with some studies indicating positive attitudes and others reflecting concerns about the potential impact on their lives 5.
• Further research is needed to validate the results and guide policies and clinicians in the integration of genetic testing into mental healthcare practice 5.

Evidence-Based Genetic Counseling

• Psychiatric genetic counseling is not yet routinely or widely offered, despite evidence that it can improve outcomes such as empowerment for patients and their families 6.
• Research shows that psychiatric genetic counseling can provide patients and their families with information and support, but further studies are needed to fully understand its clinical implications and remaining research gaps 6.