Experience With Pharmacogenetic Testing Improves Confidence Among Clinicians

Clinicians expressed greater comfort with and confidence in pharmacogenetic testing (PGx) after participation in a clinical trial that employed PGx for depressed patients, according to a report published today in Psychiatric Services.

Some clinicians were uncertain about which patients might be best served by these tests, while others expressed concerns about cost. But there was a general perception that part of the test’s value was its potential to help patients with buy-in and confidence regarding medication treatment.

“Exposure to this novel practice is necessary to help providers understand its potential usefulness and how they may apply testing results in their clinical management of patients with depression,” wrote Bonnie M. Vest, Ph.D., of the State University of New York–University at Buffalo, and colleagues.

The Precision Medicine in Mental Health Care (PRIME Care) study was a randomized controlled trial to assess whether using a commercially available PGx test improved outcomes in patients with depression. All participating clinicians completed a baseline survey between July 2017 and January 2021. The survey assessed demographic information as well as comfort with and perceptions of PGx testing rated on a five-point Likert scale.

A follow-up survey was conducted between December 2020 and March 2021 after PRIME Care concluded. A total of 217 clinicians completed both surveys, and 61 also took part in qualitative interviews. Overall, 72% of those who completed the survey and 80% of those who participated in interviews worked in specialty mental health clinics; 62% and 72%, respectively, completed medical training.

Following the trial, 31% of clinicians strongly agreed with the statement “I feel comfortable ordering a pharmacogenetic test to predict risk of adverse events or the likelihood of a treatment response” compared with 15% before the study. Further, 38% strongly agreed with the statement “I feel well informed about the role of pharmacogenetic testing in choosing a psychotropic medication” compared with 21% before the trial. Mental health clinicians were much more likely than primary care ones to provide positive answers.

Qualitative interviews revealed more nuance. One provider responded: “I do feel patients have felt more confident about trying medications with that information, so I think there is some positive value.... I wouldn’t say it’s game changing.” Another provider said: “If it’s cost-effective enough to do it at the beginning, it might be worth it just to eliminate a lot of the guesswork…. I think cost would be prohibitive as far as just doing it on every patient.”

The authors concluded: “A pressing need exists for further research, including cost-benefit analyses, to inform decisions about PGx implementation. Specifically, our findings highlight providers’ concerns about patient-level criteria and when during treatment PGx testing is most beneficial.”

For related information, see the Psychiatric News article “Pharmacogenomic Testing May Help Achieve Better Patient Outcomes, Less Toxicity.”

(Image: Getty Images/iStock/wildpixel)

---

Don't miss out! To learn about newly posted articles in Psychiatric News, please sign up here.

Follow Psychiatric News on X, LinkedIn and Instagram!

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)

---

Have You Gotten Email Requests from the AMA?

If so, the simple message is please respond. The AMA has sent out weekly reminder emails from PPISurvey@mathematica-mpr.com with the email subject line of “Reminder: The AMA needs your input to support fair and accurate physician payment.” If you have received these emails, it is urgent that you or your office staff respond as it will help the AMA gather accurate data on practice costs and the hours of patient care that physicians provide to support fair and accurate physician payment.

The study relies on financial experts in physician practices to complete the online financial information survey. The number of direct patient care hours is a critical component of the Medicare payment methodology. Participation will ensure that practice expenses and patient care hours are accurately reflected.

Pharmacogenetic-Guided Treatment Shows No Benefit Over Standard Treatment for Adolescents With MDD

Adolescents with major depressive disorder (MDD) who receive treatment guided by pharmacogenetic testing appear to show similar improvements over time as those who did not receive guided treatment, according to a report in the Journal of the American Academy of Child & Adolescent Psychiatry.

“Despite great initial enthusiasm and a surge of companies offering pharmacogenetics testing for psychiatric medications, controversy within the psychiatric field regarding the utility of pharmacogenetics testing is widespread,” wrote Jennifer L. Vande Voort, M.D., of the Mayo Clinic and colleagues. Few studies have examined whether treatment guided by such tests is associated with better outcomes in youth with depression compared with those receiving standard care.

Vande Voort and colleagues randomly assigned 176 adolescents aged 13 to 18 with moderate to severe MDD (score ≥40 on the Children’s Depression Rating Scale-Revised [CDRS-R]) to one of two groups:

• GENE: Physicians treating participants in the GENE group received the participants’ pharmacogenetic testing results at the baseline visit.
• TAU: Physicians treating participants in the treatment as usual (TAU) group did not receive the participants’ pharmacogenetic testing results until after the eight-week visit.

The participants were seen by a psychiatrist and completed assessments at baseline, weeks 4 and 8, and 6 months. These assessments included the CDRS-R, Quick Inventory of Depressive Symptomatology (QIDS), Children’s Global Assessment Scale (CGAS), and Young Mania Rating Scale (YMRS). Throughout the trial, psychiatrists were asked to record the reasons for medication decisions, such as whether the decision was based on pharmacogenetics testing or clinical judgment.

“This study found that participants in both the GENE and TAU arms improved throughout the duration of the study, and there was no statistical difference in improvement between the two arms on the CDRS-R, QIDS, and CGAS,” the authors reported. “In addition, there was no statistical difference in YMRS scores or the number of adverse events/side effects between the GENE and TAU arms throughout the duration of the study.”

The authors noted that although selective serotonin reuptake inhibitors (SSRIs) were the most frequently prescribed medications for participants in both treatment arms, the TAU arm had nearly 15% more SSRIs prescribed than the GENE arm.

“Pharmacogenetics testing held a great deal of promise as the gateway to personalized medicine. … [U]nfortunately, the field is not there yet, and clear clinical utility for commercial combinatorial platforms in adolescents with depression remains elusive,” Vande Voort and colleagues wrote. Future studies should explore “whether concordance (defined as when the clinician’s treatment recommendation matches the pharmacogenetics testing report of ‘use as directed’) is associated with greater response/remission rates or lower side effect burden when compared to nonconcordant treatment,” they advised.

For related information, see the Psychiatric News articles “Pharmacogenomic Tests in Psychiatry: Not Ready for Prime Time” and “Task Force on Gene Testing for Antidepressant Efficacy Concludes Tests Not Yet Ready for Widespread Use.”

(Image: iStock/cosmin4000)

Gene Variant Predicts Antidepressant Response and Side Effect Severity

A variant in a gene called ABCB1 can predict how a person will respond to certain antidepressants, reports a new study in AJP in Advance titled “ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial.”

The study involved 683 patients who received escitalopram, sertraline, or extended-release venlafaxine; the participants also had their ABCB1 gene sequenced. All three of these medications interact with P-glycoprotein, the protein encoded by the ABCB1 gene that functions in transporting antidepressants across the blood-brain barrier.

The authors found a variant called rs10245483 had a significant effect on remission rate and side effects, though it varied depending on the medication. People who had two copies of the common variant (G/G) responded better and had fewer side effects with escitalopram and sertraline. In contrast, people with the minor variant (T/T) responded better and had fewer side effects with venlafaxine.

The degree of remission correlated with the relative cognition of the patient. G/G participants had a greater rate of remission with escitalopram if their cognition was intact, whereas people with T/T displayed a greater rate of remission with venlafaxine if their cognition was impaired.

To read about a potential pharmacogenetic biomarker that may help inform sobriety treatment, see the Psychiatric News article “Genetic Analysis Identifies Possible Acamprosate Biomarker.”

(shutterstock/appler)

Rate of Nicotine Metabolism May Predict Best Way to Quit Smoking

How quickly a smoker metabolizes nicotine could determine which type of cessation strategy has the best chance of success, according to a new study that represents one of the largest pharmacogenetic analyses of tobacco dependence to date.

The study found that smokers with normal metabolism levels had better quit rates with varenicline therapy, which does not involve nicotine replacement, compared to a nicotine patch. For people with slow nicotine metabolism, the patch may be the better option.

It has been known for a while that smokers clear nicotine from their bodies at different rates, but until now it wasn’t known if this measurable trait--the nicotine metabolite ratio (NMR)--could be used to optimize treatment and improve outcomes.

The study researchers randomly assigned 1,246 smokers (662 slow metabolizers and 584 normal metabolizers) to 11 weeks of the nicotine patch and placebo pill, varenicline and placebo patch, or double placebo; all participants also received behavioral counselling.

After 11 weeks of treatment, normal metabolizers taking varenicline were about twice as likely not to smoke as those using the nicotine patch. And while slow metabolizers displayed similar effectiveness rates on varencline or the patch, they reported far fewer side effects for patch therapy.

To read more about how smoking cessation leads to improved mental health, see the Psychiatric News article "Smoking Cessation Bestows Multiple Mental Health Benefits." Also, to learn about a potential new adaptive cessation strategy, see the American Journal of Psychiatry study "Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation Paradigm."

(shutterstock/bikeriderlondon)

Ondansetron May Be Effective in Treating Alcoholism in Certain Populations, Study Finds

Taking a more personalized approach to treatment for mental illness, several studies are investigating whether patients’ genetic makeup can help physicians more effectively treat chronic illnesses, including substance use disorders. A study in the American Journal of Psychiatry titled "Determination of Genotype Combinations That Can Predict the Outcome of the Treatment of Alcohol Dependence Using the 5-HT₃ Antagonist Ondansetron" showed that ondansetron—a FDA-approved nausea medication—can help treat alcohol dependence among a certain population with serotonergic protein variances.

Researchers at the University of Virginia divided 283 alcohol-dependent subjects into two groups—one group received ondansetron and the other received placebo. Participants were tested for 21 polymorphisms for the HTR3A and HTR3B genes—subunits of serontonin-3 receptors (5-HT3)—in addition to variances in the serotonin transporter gene, SLC6A4. Drinking days and days abstained from alcohol were evaluated.

Results showed that ondansetron participants with specific polymorphisms for HTR3A/HTR3B genes had a 20 percent lower incidence of heavy drinking days and were twice as likely to abstain from alcohol as were those with the same polymorphisms taking placebo. In addition, a subpopulation of individuals carrying a combined genotype variance for SLC6A4 and HTR3A/HTR3B were able to reduce drinking days by 34 percent while taking ondansetron, whereas individuals expressing SLC6A4 variances alone reduced drinking days by 20 percent.

“The era of personalized medicine by which we can target subpopulations of those with alcohol dependence for optimum treatment effect has arrived,” Bankole Johnson, M.D., lead author and a professor of psychiatry at the University of Virginia, told Psychiatric News. He noted that more clinical trials are needed to replicate the current findings.

For more about this study, see the Psychiatric News article “Genes May Determine Drug’s Alcohol-Treatment Success.”

(Image courtesy of hospira.com)