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This analysis of the GUIDED clinical trial identified statistically significant improvements in remission, response, and symptoms at week 8 between GeneSight-guided care and treatment as usual. This comparison was done using the HAM-D6 scale, a subset of the HAM-D17 scale that focuses on core depressive symptoms. While both versions of the scale showed significant differences for the response and remission outcomes, the greater differences for symptom improvement using HAM-D6 may suggest that HAM-D6 provides a more precise measure for MDD outcome assessment.
This large study, like PRIME Care, looked at the impact of the GeneSight test in choosing medication for depressed patients. Results showed a modest 5-7 percentage-point gain in overall response and remission rates, an effect mirroring prior research. However, for patients with “red bin” results, the study suggests that the test may hold more value. For this group, the risk of serious side effects was decreased, and improvement in response and remission rates was significantly increased (roughly 12-13 percentage-points over treatment as usual). With its intended total of 2,000 subjects, PRIME Care is likely to build on the reliability of what we are learning about PGx testing—including its value in treating patients whose tests come back with worrisome potential drug-gene interactions.
This paper describes the results of a prospective, randomized, subject- and rater-blinded approach enrolling 685 patients from clinical providers in a variety of specialties, including Psychiatry, Internal Medicine, Obstetrics & Gynecology, and Family Medicine. In patients diagnosed with depression, response and remission rates were significantly higher in the pharmacogenetics-guided group as compared to the control group at 12 weeks.
The results of this Spanish study, which was much smaller in scope than PRIME Care, suggest that patients whose prescribers have access to PGx findings when picking an antidepressant are about 10% more likely to respond to treatment. The patients in the PGx condition reported significantly fewer side effects than patients in the treatment as usual condition. Moreover, the advantage in response rates increased to 15% when the analysis was limited to those patients whose prescribers followed the recommendations of the PGx assessment.
This prospective, randomized study included 237 patients with a range of neuropsychiatric disorders (including depression, anxiety, ADHD, and psychosis) at outpatient psychiatric clinics. The study found that PGx-guided medication management reduced the occurrence of adverse drug events, but it did not find any statistical difference in efficacy. The PGx-guided group of patients had 84% lower health care costs compared to the control group.
This publication describes the results of a 12-week, prospective, double-blind, randomized trial of genetically guided versus unguided antidepressant dosing in Caucasian adults with MDD. The study found that subjects receiving genetically guided prescribing had a 2.52-fold greater chance of remission than those receiving unguided prescribing.
This paper describes the result of a prospective, randomized, double-blind study evaluating the benefit of a combinatorial, five-gene test and interpretative report for the management of psychotropic medications used in the treatment of major depression in an outpatient psychiatric practice. The study found that pharmacogenetic-guided treatment doubled the likelihood of response in all patients with treatment-resistant depression.
This multicenter study, which was conducted in both primary and specialty care sites across Canada, used an “open” or descriptive design; unlike the VA PRIME Care Study, there is no control group. Overall, the patients who received “congruent treatment” (i.e., they received a medication listed in the “green” column), obtained a better outcome (a 31% relative advantage in symptom improvement) than did the patients whose treatment did not follow the PGx findings. Interestingly, the value of PGx testing was significantly larger for the patients treated in primary care compared to specialty care. This might mean the guidance provided by drug-gene testing was more helpful for physicians with less comfort/experience with prescribing the full range of antidepressant options. It will be interesting to see if the patients treated by primary care prescribers in the PRIME Care study will show a similar advantage under more methodology rigorous conditions.
This paper describes the results of an open-label study wherein subjects were divided into guided and unguided groups. The guided group experienced greater percent improvement in depression from baseline than the unguided group. Eight-week response rates and eight-week remission rates were also higher in the guided group, leading to the authors' conclusion that use of an integrated, multigenic pharmacogenomic testing platform significantly improves depression outcomes.
This paper describes the results of a non-randomized, open-label, prospective cohort study of treatment that is guided or unguided by a pharmacogenomic test report. While the authors note that the results of this small pilot study provide a preliminary suggestion that there may be a benefit to pharmacogenomic testing in mental health care, they conclude that more research is needed to increase confidence in the findings and better understand the factors associated with improved outcomes.
This paper describes the results of genome-wide association studies in a relatively large Scottish cohort of people who had taken antidepressants and a very carefully assessed clinical sample. The authors were unable to identify any reliable genetic correlates of antidepressant response. These starkly negative findings underscore that antidepressant response is largely not mediated by genetic factors. The clinical sample is relatively small, and the method used to classify treatment resistance in the Scottish cohort was suboptimal (symptoms were not measured during treatment, and the method lumped together nonadherence and intolerance to side effects with nonresponse). Nevertheless, the design was sensitive enough to detect associations between self-reported measures of psychological distress, emotional reactivity, and several personality traits and antidepressant response. As antidepressant nonresponse is multi-determined, and the likely effects of pharmacogenomics are small, these results highlight the importance of careful, prospective studies such as PRIME Care to ascertain the predictive value of testing and, if value can be confirmed, estimate cost-effectiveness.
The recommendations of this independent narrative review in the American Journal of Psychiatry underscore the conclusions of DoD and VA review groups from a few years ago. To date, there is not sufficient evidence to recommend widespread use of pharmacogenetic testing to guide antidepressant therapy. The results of PRIME Care study, with its inclusive enrollment criteria and pragmatic research design, will likely play a major role in adding to the evidence evaluating the utility and cost-effectiveness of pharmacogenetic testing.
This invited review evaluates the Late-Life Depression (LLD) pharmacogenetic evidence base and the extent to which this was incorporated into existing commercial decision support tools and clinical pharmacogenetic guidelines.
This analysis included four randomized controlled trials and two open-label controlled cohort studies, which together totaled over 1,300 subjects. When compared to the patients who received “treatment as usual,” the patients whose medication selection and/or dosing was informed by pharmacogenetic testing were significantly more likely to respond and remit. Overall, the absolute value of using PGx test results to help select the next antidepressant medication was modest, and there was significant variability in the benefit across the studies, which themselves differed considerably in terms of the types of genetic tests administered, how the results were used, the demographic and clinical characteristics of the participants, and the range of specialties among the treatment providers. The analysis points out that, in addition to continued research into the overall clinical utility of PGx for treating depression, more investigation is also needed to assess its “cost-effectiveness” (the cost of the test versus the costs associated with a longer time until response or remission), its value to treatment-resistant versus new-to-treatment patients, and its benefits to specific ethnicities.
This article is a response to the previous letter to the editor about the article, "Combinatorial pharmacogenomics and improved patient outcomes in depression: Treatment by primary care physicians or psychiatrists."
The Clinical Pharmacogenetics Implementation Consortium is an international consortium working on facilitating use of pharmacogenetic tests for patient care. Follow the links below for more information.