“[G]uided-care showed significantly improved response (Δ=13.6%, t=2.16, df=187; p=0.032) and remission (Δ=12.7%, t=2.49, df = 189; p=0.014) relative to TAU. By week 8, more than twice as many patients in guided-care than in TAU were on medications predicted to have no gene-drug interactions […].”

“Although previous meta-analyses have demonstrated the utility of pharmacogenomic testing, the generalizability of those findings are limited by substantive differences in the individual pharmacogenomic tests. This meta-analysis of four studies reporting on the clinical utility of GeneSight Psychotropic testing demonstrates that utilization of this pharmacogenomic test to inform treatment decisions for patients with MDD with at least one prior medication failure is associated with improved patient outcomes compared with unguided care. This was true for all patient outcomes evaluated, including symptom improvement, response and remission.”

“The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms.”

“By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure.”

“[T]his randomized controlled trial found that weighted and combined multi-gene pharmacogenomic testing significantly increased clinical response and remission rates for patients with Major Depressive Disorder in the guided-care arm versus Treatment As Usual. Pharmacogenomic testing predominantly helped those patients whose treatment resistance may have been related to genetically incongruent medications. Without testing, patients and clinicians are unaware of potential ongoing gene-drug interactions.”

“When outcomes were considered separately for patients < 65 and ≥ 65 years of age, all outcomes were significantly improved for patients treated by primary care providers compared to psychiatrists, regardless of age group.”

“In the GeneSight arm, 36.0% of subjects were responders, which was defined as a 50% reduction in HAMD-17 at ten weeks, compared to 20.8% in the TAU [treatment as usual] arm (OR=2.14; 95% CI: 0.59-7.69). In the GeneSight arm, 20.0% achieved remission, defined as HAMD-17 less than or equal to 7, at ten weeks compared with the TAU arm at 8.3% (OR=2.75; 95% CI: 0.48-15.80).”

“The guided group experienced greater percent improvement in depression scores from baseline on all three depression instruments […] compared with the unguided group. Eight-week response rates were higher in the guided group than in the unguided group on all three measurements […]. Eight-week QIDS-C16 remission rates were higher in the guided group (P = 0.03). Participants in the unguided group who at baseline were prescribed a medication that was most discordant with their genotype experienced the least improvement compared with other unguided participants (HAMD-17, P = 0.007). Participants in the guided group and on a baseline medication most discordant with their genotype showed the greatest improvement compared with the unguided cohort participants (HAMD-17, P = 0.01).”

“The reduction in depressive symptoms achieved within the guided treatment group was greater than the reduction of depressive symptoms in the unguided treatment group using either the QIDS-C16 (P¼0.002) or HAM-D17 (P¼0.04).”

“Providing clinicians with the GeneSight interpretive report improved the proportion of antidepressant responders by 71% as compared with unguided patients. A 2.26-fold increase in the odds of clinical response was also found for the guided patients as compared with the unguided patients. These improvements paralleled changes in drug dosing or selection, in that a greater proportion of guided patients experienced medication changes. These changes resulted in 40% of the guided patients initially on red-category medications being shifted to yellow- or green-category medications, and 35% more patients prescribed green-category medications, by the study end.”

“In summary, this evaluation of clinical validity shows that only the combinatorial pharmacogenomic test was significantly associated with improved patient outcomes. In addition, the combinatorial pharmacogenomic test was a superior predictor of medication blood levels across a larger group of medications relative to guidelines focused on only CYP2C19 and CYP2D6.”

“With this combinatorial pharmacogenomic test, more patients were identified as appropriate candidates for clinically actionable dosing changes for citalopram and escitalopram from comprehensive and predictive information compared to single-gene testing and CPIC classifications.”

“Multigenic combinatorial testing discriminates and predicts the poorer antidepressant outcomes and greater health-care utilizations by depressed subjects better than do phenotypes derived from single genes.”

“[C]ombinatorial pharmacogenomics test […] aid[s] in the appropriate medication selection for neuropsychiatric conditions. This study demonstrates that the combinatorial pharmacogenomics test is robust and reproducible, making it suitable for clinical use.”

“The benefit of pharmacogenetic-informed prescribing is not distributed uniformly across a cohort but is derived from a minority of patients.”

“Between 10/6/2014 and 2/1/2018, 181 veterans underwent psychotropic PGx testing. The majority (68%) had a diagnosis of depression and 12% had a diagnosis of schizophrenia or bipolar disorder. Provider actions trended towards starting green bin medications and stopping red bin medications, although there were exceptions.”

“Individuals receiving pharmacogenetic-guided DST therapy (n = 887) were 1.71 (95% CI: 1.17–2.48; p = 0.005) times more likely to achieve symptom remission relative to individuals who received treatment as usual (n = 850). Pharmacogenetic-guided DSTs might improve symptom remission among those with MDD.”

“The level of disagreement in medication recommendations across the pharmacogenetic decision support tools (DSTs) indicates that these tests cannot be assumed to be equivalent or interchangeable.”

“According to the published literature, HAM-D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability (each item contains unique information regarding syndrome severity), transferability (scalability is constant over time and irrespective of sex, age, and depressive subtypes), and responsiveness (sensitivity to change in severity during treatment).”

“Treatment-resistant depression exacts a heavy price in treatment costs and lost productivity, reaching into the tens of billions of dollars, but its effects on the lives of patients are just as devastating. In this literature review, the authors summarize 62 studies documenting the disease’s toll on quality of life, personal financial resources, and general health. The average patient in the included studies had experienced nearly four earlier episodes of depression, had not responded to 4.7 drug trials, and continued to meet or nearly meet criteria for severe depression.”

“The classification of TRD had a clinically meaningful and statistically significant association with increased medical expenditures. Holding all else equal, the classification of TRD was associated with a 29.3% higher costs (P < 0.001) in medical expenditures compared with patients not meeting the study definition of TRD.”

“With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%.”

“Compared with major depressive disorder (MDD) controls, TRD-likely employees had significantly higher rates of mental-health disorders, chronic pain, fibromyalgia, and higher Charlson Comorbidity Index. Average direct 2-year costs were significantly higher for TRD-likely employees ($22,784) compared with MDD controls ($11,733), p < 0.0001. Average indirect costs were also higher among TRD-likely employees ($12,765) compared with MDD controls ($6885), p < 0.0001.”

“The average annual cost of employees considered TRD-likely was dollars US 14490 per employee, while the cost for depressed but TRD-unlikely employees was dollars US 6665 per employee, and dollars US 4043 for the employee from the random sample. TRD beneficiaries used more than twice as many medical services compared with TRD-unlikely patients, and incurred significantly greater work loss costs.”

“Providers recommend, and patients request, ECS carrier screening outside of guidelines criteria, and patients take action to reduce the risk of an affected pregnancy regardless of whether they meet the criteria for screening.”

“ECS results impacted couples’ reproductive decision-making and led to alterned pregnancy management that effectively eliminates the risk of having affected offspring.”

“We observe 99% concordance at the level of unique variants.”

“ACOG’s 1-in-100 criterion limits at-risk couple detection and should be reconsidered.”

“The described approaches enable principled, quantitative evaluation of which diseases and methodologies are appropriate for pan-ethnic expanded carrier screening.”

“In a population of diverse races and ethnicities, expanded carrier screening may increase the detection of carrier status for a variety of potentially serious genetic conditions compared with current recommendations from professional societies.”

“Disease severity is a key criterion for carrier screening. Expanded carrier screening…requires an objective, systematic means of describing a given disease’s severity to build screening panels.”

“Modern NGS and variant interpretation enable accurate sequencing-based CF screening.”

“Validated high-fidelity identification of different variant types—especially for diseases with complicated molecular genetics—maximizes at-risk couple detection.”