Genetic testing has been hailed for helping to tailor depression treatment. Theoretically, people could be genetically suited for some specific drugs and less suited for others. We can now guide the choice of antidepressants based on genetic testing. But does this lead to better results?

Not according to a new study in JAMA network open. The researchers tested whether an antidepressant choice guided by genetic testing was better than antidepressant choice with normal clinical judgment. They found that genetic testing did not affect the effectiveness of antidepressants: 24 percent of participants responded to treatment, and response rates were similar whether or not they received testing.

No significant difference was seen in the reduction of depressive symptoms, the researchers write.

That low response rate is especially surprising, given that recent studies have found much higher responses to placebo. For example, a Cochrane review found a 42% response rate for drug placebo treatment, even for major depression, and a ketamine infusion study found a 57.9% response rate for a placebo active.

brain against blue dna strand with chemical structuresThe research was conducted by Cornelis F. Vos and Sophie E. ter Hark at Radboud University Medical Center, Nijmegen, The Netherlands. The study included 56 patients randomly assigned to receive antidepressant choice guided by genetic testing and 55 patients who received treatment as usual (antidepressant choice guided by clinical judgment). All patients received tricyclic antidepressants.

In the genetic testing group, the researchers evaluated the patients CYP2D6 AND CYP2C19 genotypes and determined the starting dose of antidepressants based on these results.

According to the researchers, the main outcome was whether genetic testing helped the drugs achieve therapeutic plasma concentrations. They found that about 80% of both groups achieved this level. However, those who received a drug guided by genetic testing achieved therapeutic plasma concentrations more quickly: after 17 days rather than 22 days, on average.

The other outcomes the researchers assessed were changes in depressive symptoms and adverse effects. The researchers found that genetic testing does not increase the likelihood that the drugs will work, with both groups experiencing low response rates. Similarly, the researchers found no difference in adverse effects, on average.

However, they suggest their study supports the idea that genetic testing can help reduce the harmful side effects of drugs over time.

In the first four weeks of antidepressant use, those on antidepressants chosen via genetic testing did so more severe adverse effects of drugs. However, in weeks 5 to 7, those who underwent genetic testing experienced less severe side effects. Therefore, the researchers conclude that choosing a drug based on genetic testing may shorten the length of time people experience harmful side effects (or reduce the severity over time). However, since the study ended after seven weeks, we can’t see if this pattern holds true for more than those final three weeks.

In summary, the study showed that personalized treatment based on genetic testing did not, on average, lead to an improvement in depressive symptoms or fewer harmful effects, but that there was a potential signal for a reduction in the severity of side effects. in time. Furthermore, the number of people who responded to antidepressants was far fewer than would be expected, even if the subjects had received a placebo.

What conclusion should we draw from this? The researchers write that their study was a success:

These results indicate that pharmacogenetic-based tricyclic antidepressant dosing can be applied safely and contributes to personalized antidepressant treatment.

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Vos, CF, ter Hark, SE, Schellekens, AFA, Spijker, J., van der Meij, A., Grotenhuis, AJ, . . . & Janzing, JGE (2023). Dosage efficacy of genotype-specific tricyclic antidepressants in patients with major depressive disorder: a randomized clinical trial. JAMA Network Open, 6(5), e2312443. doi:10.1001/jamanetworkopen.2023.12443 (Link)

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