Friday, May 3, 2024

Evidence Base for Pharmacogenetic Tests Still Lacking, APA Workgroup Finds

There is still not enough evidence to support the use of pharmacogenetic tests in the treatment of depression, according to updated recommendations from APA’s Workgroup on Biomarkers and Novel Treatments. The recommendations were published in AJP in Advance.

Pharmacogenetic tests analyze an individual’s genes (obtained via blood, saliva, or cheek swabs) to find genetic variants that may influence how fast antidepressants are metabolized or how well they attach to their receptors. Using special algorithms, the tests then calculate the combined impact of all the variants and offer readouts of antidepressants that might be effective and others to avoid.

In 2018, APA’s Council on Research organized a workgroup to examine the available data on pharmacogenetic tests for depression; the workgroup concluded that there was insufficient evidence to support the widespread use of pharmacogenetic tools in clinical practice. Subsequently, both the FDA and International Society of Psychiatric Genetics voiced concerns about these tests.

“Despite expert opinions, warnings, and policy statements regarding their limitations for predicting antidepressant treatment response, the popularity of [pharmacogenetic] testing products has grown, with at least 35 U.S. commercial entities providing them by 2020,” wrote the APA workgroup members in their updated recommendations.

The workgroup examined data from 11 pharmacogenetic clinical trials conducted between 2017 and 2022, as well as six meta-analyses that combined individual results. “The main new contribution of these studies is one of numbers: several trials have included relatively large sample sizes, and >4,000 patients have now participated in [pharmacogenetic] studies,” they wrote.

Though most of the trials demonstrated that using a pharmacogenetic test increased the likelihood that a patient would respond to their antidepressant, these new studies did not address previous shortcomings, the workgroup continued. None of the new trials were fully blinded (neither patients nor investigators were aware who was receiving a test), which increases the risk of bias in decision making. Further, the control group in these studies was to provide treatment as usual, but little attention was given to ensuring clinicians were providing the best standards of depression care.

Finally, all studies were fully or heavily supported by the pharmacogenetic industry. “[A]lthough industry support is not in itself problematic and historically has often been integral in completing large, well-designed, definitive trials, its coexistence with the methodological concerns reviewed above augments the concern about bias,” the workgroup wrote.

“Genetic approaches remain promising, and we look forward to future studies and advances in the field,” the APA workgroup concluded. “However, we advise devoting greater attention to implementing study designs consistent with other studies of treatment interventions.”

For related information, see the Psychiatric News story, “Pharmacogenomics Can Inform ‘Big Data’ Projects.”

(Image: Getty Images/iStock/Alena Butusava)

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