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Objective Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD). Design Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms. Setting Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites. Participants Adults age 65 years or older at baseline (n = 206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode. Intervention Combinatorial pharmacogenomic testing to inform medication selection (guided-care), compared with treatment as usual (TAU). Outcomes Mean percent symptom improvement, response rate, and remission rateat week 8, measured using the 17-item Hamilton Depression Rating Scale; medication switching; and comorbidity moderator analysis. Results At week 8, symptom improvement was not significantly different for guided-care than for TAU (∆ = 8.1%, t = 1.64, df = 187; p = 0.102); however, guided-care showed significantly improved response (∆ = 13.6%, t = 2.16, df = 187; p = 0.032) and remission (∆ = 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 (χ2 = 19.3, df = 2; p Conclusions Combinatorial pharmacogenomic test-informed medication selection improved outcomes over TAU among older adults with depression.

Mood disorders are among the most burdensome public health concerns. The National Network of Depression Centers (NNDC) is a nonprofit consortium of 26 leading clinical and academic member centers in the United States providing care for patients with mood disorders, including depression and bipolar disorder. The NNDC has established a measurement-based care program called the Mood Outcomes Program whereby participating sites follow a standard protocol to electronically collect patient-reported outcome assessments on depression, anxiety, and suicidal ideation in routine clinical care. This article describes the approaches taken to develop and implement the program.Since 2015, eight pilot sites have implemented the program and followed more than 10,000 patients. This pilot study presents descriptive statistics based on the first 24-month period of data collection.In this sample, 58.6% of patients with bipolar disorder (N=849) and 57.5% of patients with unipolar depression (N=3,998) remained symptomatic at follow-up. Lifetime rates of planned or actual suicide attempts were high, ranging from 27.6% for patients with unipolar mood disorders to 33.5% for patients with bipolar disorder. Men, unmarried individuals, and those with comorbid anxiety had a poorer longitudinal course. This initial snapshot of clinical burden is consistent with public health data indicating that mood disorders are severely debilitating.This study demonstrates the potential of the Mood Outcomes Program to create a nationwide "learning health system" for mood disorders. This goal will be further realized as the program expands in reach and scope across additional NNDC sites.

According to the World Health Organization, major depressive disorder is the world’s leading cause of disability. If clinical remission is not attained and sustained, episodes tend to recur with greater severity and with lessening responsivity to conventional treatments. Reasonably well-established clues and guidelines are presented about the high risk and profound consequences of recurrence of major depressive disorder if successful antidepressant treatments are discontinued. The authors describe actions required to achieve a “lifetime wellness” focus for treatment. Current approaches would need to be transformed from attainment of clinical remission to attainment and maintenance of lifetime wellness, with the knowledge that some individuals may need continuous treatment. Risk factors would need to be assessed and used to formulate clinical treatment guidelines for risk of recurrence. Clinical trials would need to be greatly lengthened. Measurement-based care and precision medicine would be the foundation for informing clinical decisions. The authors provide guidance in determining how to discontinue antidepressants if that decision is made despite risks.

Weight gain is a common side-effect of medications used to treat major depressive disorder (MDD). We sought to estimate the frequency of weight gain for obesogenic medications prescribed for MDD and to evaluate if bupropion mitigated risk for weight gain. We analyzed a prospective cohort of patients with weight available at baseline and 12 weeks (n = 1,032) or 24 weeks (n = 871) in a post hoc analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) study of patients with MDD who failed at least one medication trial. We compared weight gain between those on versus not on medications with high risk for weight gain, including a subgroup receiving combination treatment with bupropion. A second analysis evaluated weight gain across traditional medication classes, adjusting for potential confounding variables. Those on medications identified as high risk for weight gain were significantly more likely to experience clinically significant weight gain (≥3%) at 12 weeks (29.3% vs. 16.3%, p < .001) and 24 weeks (33.5% vs. 23.5%, p = .015). No protection from clinically significant weight gain was observed among patients treated with a high-risk medication concomitantly with bupropion (N = 31, 35% and 52% with clinically significant weight gain at 12 and 24 weeks). Antipsychotic medications and tricyclic antidepressants were most often associated with clinically significant weight gain. This study helps quantify the real-world risk of weight gain for patients with MDD on medications with high risk for weight gain, especially for patients taking antipsychotics. Concurrent treatment with bupropion does not appear to mitigate the weight gain risk.

The efficacy of subanesthetic intravenous ketamine for treatment resistant depression (TRD) has spurred a growth of clinics nationwide that provide this service. Ketamine is an FDA-approved drug as an anesthetic but remains unapproved for psychiatric indications, and this status raises a number of short- and long-term safety and efficacy concerns that need to be addressed when implementing and developing this type of clinic. Using a framework of systems, provider, and patient domains, we provide a review of the key challenges in providing ketamine infusions and suggest potential approaches. Under systems issues, we highlight broad stakeholder engagement involving cross-departmental and multidisciplinary considerations, business case development, and delineation of administrative standard operating procedures. In the provider domain, we highlight specific roles for different treatment team members as well as suggested training requirements. In the patient domain, we identify a variety of standard operating procedures involving initial patient assessment parameters, ketamine dosing and administration guidelines, and safety monitoring procedures. Together, this review provides key considerations for developing a ketamine clinic for depression, in an effort to meet the pressing demand for this novel treatment option while helping to ensure its safe implementation.

Pharmacogenomic testing can be used to guide medication selection in patients with major depressive disorder (MDD). Currently, there is no consensus on which gene or genes to consider in medication management. Here, we assessed the clinical validity of the combinatorial pharmacogenomic algorithm to predict sertraline blood levels in a subset of patients enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial. Patients who reported taking sertraline within ≤2 weeks of the screening blood draw were included. All patients received combinatorial pharmacogenomic testing, which included a weighted assessment of individual phenotypes for multiple pharmacokinetic genes relevant for sertraline (CYP2C19, CYP2B6, and CYP3A4). Sertraline blood levels were compared between phenotypes based on: 1) the pharmacokinetic portion of the combinatorial pharmacogenomic algorithm, and 2) individual genes. When evaluated separately, individual genes (for CYP2C19 and CYP2B6) and the combinatorial algorithm were significant predictors of sertraline blood levels. However, in multivariate analyses that included individual genes and the combinatorial pharmacogenomic algorithm, only the combinatorial pharmacogenomic algorithm remained a significant predictor of sertraline blood levels. These findings support the clinical validity of the combinatorial pharmacogenomic algorithm, in that it is a superior predictor of sertraline blood levels compared to individual genes.

Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial – a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent (‘use as directed’ or ‘use with caution’ test categories) or incongruent (‘use with increased caution and with more frequent monitoring’ test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).

We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.

Background Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. Methods This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. Results At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. Conclusions 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. Trial registration Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.

BackgroundPharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).Materials and MethodsPatients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.ResultsMost patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.ConclusionThese data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.FundingMyriad Neuroscience/Assurex Health

Introduction Six million people in the U.S. experience depression after age 65. Major depressive disorder (MDD) in later life is associated with longer length of illness, increased number of MDD episodes, and a greater risk of comorbidities. Challenges facing clinicians when making prescription decisions for older adults include increased drug-drug interactions, lower adherence, and higher rates of adverse events. Medication trials for MDD can be difficult to navigate in older patients due to increased polypharmacy for multiple conditions. As the aging population grows, the demand for data-driven tools to optimize medication prescribing for older patients with MDD is gaining momentum. Combinatorial pharmacogenomic (PGx) testing may improve and personalize medication prescribing for older patients by identifying medications that have patient-specific adverse gene-drug interactions. Methods The GUIDED study was a blinded, randomized controlled trial which sought to evaluate the use of a combinatorial PGx test in improving outcomes for patients with MDD by guiding medication treatment decisions. Patients were randomized to either the guided-care arm where the combinatorial PGx test result was available to providers to guide treatment decisions or to the treatment as usual (TAU) arm where the test result was not available to providers until after the primary endpoint. Both patients and raters were blinded to the arm until after the completion of the primary endpoint week 8 assessment. The primary endpoint was symptom improvement on the 17-Item Hamilton Depression Rating Scale (HAM-D17). Secondary endpoints included response (50% reduction in HAM-D17 from baseline) and remission (score ≤7 on HAM-D17). In this subanalysis, we evaluated whether patients aged 65 and older had differences in outcomes based on treatment guidance from combinatorial PGx testing. Results In the GUIDED study, 206 patients were 65+ years of age at baseline with a median age of 69; 108 patients in the treatment as usual (TAU) and 98 patients in the guided-care arm (combinatorial PGx test). The mean HAM-D17 score at baseline overall was 19.8 for all patients, 20.2 in the TAU arm and 19.4 in the guided-care arm. The average number of failed medication trials was 3.5 (3.7 in TAU and 3.3 in guided-care). At week 8, there was a 26.7% decrease in HAM-D17 scores in the guided-care arm (n=86) compared to an 18.7% decrease in TAU (n=98). The difference in symptom improvement between arms did not reach statistical significance (p=0.102). Response rate was significantly higher in the guided-care arm at week 8, with 29.6% of patients experiencing response, compared to 16.1% in TAU (p=0.032). The remission rate was also significantly higher in the guided-care arm at week 8 (20.1%), compared to TAU (7.4%, p=0.014). Conclusions Patients who were 65?years or older in the GUIDED trial whose medication treatment was guided by combinatorial PGx testing achieved significantly better response and remission rates compared to TAU. The difference in symptom improvement in this population did not reach statistical significance. Overall, the data presented here support the utility of using combinatorial PGx testing to help guide antidepressant medication selection with a goal to improve outcomes of depression. This research was funded by: Myriad Genetics, Inc.

Background:The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.Methods:Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).Results:At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).Conclusions:Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.Funding Acknowledgements:Assurex Health, Inc.

OBJECTIVE The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. METHODS Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depre​ssion Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P = .069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. RESULTS Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P = .029; response: 27.0% versus 19.0%, P = .008; remission: 18.2% versus 10.7%, P = .003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P = .011 for symptom improvement, P = .011 for response, P = .008 for remission). CONCLUSIONS 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. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02109939​.

Depressed, anxious, stressed, sleep-deprived, or substance-using workers are unproductive, accident-prone, and plagued by mistakes, sick leave, and departures. Workplace mental health issues are huge cost burdens for businesses. CEOs, managers, supervisors, human resource teams, boards of directors, and employees and their families all crave solutions. The contributors to this book collaborated to create a roadmap for business leaders and staff members to address the problems and costs of unhealthy minds at work. This introductory chapter summarizes big picture challenges and strategies. Authors of subsequent chapters review the most important workplace clinical problems and evidence-based programs to help overcome stigma; when and where to turn for clinical help when necessary; advice about structuring policies, benefits, and educational programs and supports to enhance employee utilization; how to best train and utilize supervisory and peer-to-peer interventions; and strategies for monitoring cost-effectiveness. For businesses that accept the challenge, establishing and sustaining comprehensive workplace mental wellness programs will become points of pride and profitability.

Most psychiatric syndromes are chronic and lifetime in course. Kraepelin's seminal work pointed out a century ago that longitudinal/lifetime assessments were powerful aids in differentiating dementia praecox from manic-depressive disorder. Despite this, clinical research investigations in psychiatry have historically emphasized short-term and cross-sectional approaches. This review of an array of longitudinal studies supports that they are arguably an essential component of psychiatric investigations, but that they must be coupled with other approaches. The use of standardized, validated, repeated assessments in a disease over the course of time must be incorporated with pathophysiology investigations to identify underlying mechanisms, biomarker studies, comparative effectiveness clinical trials to identify the best treatments for different causes, and translational strategies to provide the right treatments to the right patients at the right time. Strategies for incorporating longitudinal assessments into newer diagnostic proposals, such as the Research Domain Criteria (RDoC), are discussed.

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) trial who were taking citalopram/escitalopram at screening and had available blood level data were included (N=191). In multivariate analysis of the individual genes and combinatorial pharmacogenomic test separately (adjusted for age, smoking status), the F statistic for the combinatorial pharmacogenomic test was 1.7 to 2.9-times higher than the individual genes, showing that it explained more variance in citalopram/escitalopram blood levels. In multivariate analysis of the individual genes and combinatorial pharmacogenomic test together, only the combinatorial pharmacogenomic test remained significant. Overall, this demonstrates that the combinatorial pharmacogenomic test was a superior predictor of citalopram/escitalopram blood levels compared to individual genes.

Poster abstracts are evaluated based on the following criteria: significance of the problem to healthy aging or medication management; innovativeness of ideas, methods, and/or approach; methodological rigor of methods and approach; presentation of finding; implications identified for future research, practice, and/or policy; and clarity of writing. Submissions are not evaluated through the peer-reviewed process used by

The Peer-to-Peer Depression Awareness Program (P2P) is a school-based program that aims to decrease mental illness and promote well-being among students by empowering high school students as both learners and educators. Specific goals include improving the school climate around mental health, directing students to resources, and encouraging help-seeking behavior.In the 2015-2016 academic year, 121 students across 10 high schools organized into teams and were trained to develop and implement peer-to-peer depression awareness campaigns. Outcomes were assessed via pre- and posttest questionnaires.A total of 878 students completed questionnaires. Outcomes demonstrated improved knowledge and attitudes toward depression, increased confidence in identifying and referring peers with depression, improved help-seeking intentions, and reduced stigma.The P2P program increased depression literacy through the use of youth-designed and youth-implemented depression awareness and outreach activities, which may ultimately result in earlier detection of depression and in fewer depression sequelae.

Electroconvulsive therapy (ECT) is a safe and highly effective treatment for management of acute episodes of a variety of serious mental disorders, particularly for major depressive episodes that are resistant to multiple interventions with treatment alternatives. As such, the National Network of Depression Centers (NNDC), a consortium of major academic centers with interest and expertise in this area, believes there is an important public health need for ECT to remain available for clinical use. As with all medical devices, ECT is regulated by the US Food and Drug Administration (FDA), which is presently involved in formulating a proposed rule as to how such devices should be classified. Since such classification may have substantial effects on the availability of ECT to patients for whom it is clinically indicated, the NNDC has reviewed the information provided by the FDA to its Advisory Panel, as well as the subsequent deliberations of the Panel itself at a January 2011 public hearing. This review indicates that the FDA may have substantially underestimated the efficacy of ECT as a means to produce large clinical improvements for individuals suffering from severe major depressive disorders and that such an underestimate likely affected the Panel's willingness to recommend reclassification of ECT devices to a less restrictive category. In addition, the NNDC's review generates support for a variety of methods by which the safety of ECT can be ensured, which is an essential requirement for such reclassification.

Citizen soldiers (National Guard and Reserves) represent approximately 40% of the two million armed forces deployed to Afghanistan and Iraq. Twenty-five to forty percent of them develop PTSD, clinical depression, sleep disturbances, or suicidal thoughts. Upon returning home, many encounter additional stresses and hurdles to obtaining care: specifically, many civilian communities lack military medical/psychiatric facilities; financial, job, home, and relationship stresses have evolved or have been exacerbated during deployment; uncertainty has increased related to future deployment; there is loss of contact with military peers; and there is reluctance to recognize and acknowledge mental health needs that interfere with treatment entry and adherence. Approximately half of those needing help are notreceivingit.Toaddressthisconstellationofissues,aprivate‐publicpartnershipwasformedundertheauspicesof the Welcome Back Veterans Initiative. In Michigan, the Army National Guard teamed with the University of Michigan and Michigan State University to develop innovative peer-to-peer programs for soldiers (Buddy-to-Buddy) and augmented programs for military families. Goals are to improve treatment entry, adherence, clinical outcomes, and to reduce suicides. This manuscript describes training approaches, preliminary results, and explores future national dissemination.

OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies in studies of psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this brief report and the accompanying full article from which it is distilled. The full article was developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement at the conference have been noted in the text. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed. Language: en

Objective: The National Institute of Mental Health (NIMH) determined that declines in the psychiatrist-researcher workforce are harming public needs and that significant steps are necessary to alter current trends. Method: The NIMH commissioned the Institute of Medicine (IOM) to examine the undersupply and recommend solutions. The NIMH subsequently appointed a National Psychiatry Training Council (NPTC) to facilitate implementation of the IOM’s recommendations. Results: The IOM recommendations and preliminary NPTC actions to address them are described. Conclusions: Increasing the psychiatrist-researcher workforce will require interventions involving many institutions. The NPTC’s efforts may offer practical solutions for approaching complex and admittedly challenging difficulties.

Central serotonin function was studied among 21 adolescents (12 males, 9 females), mean age 14.4+/-1.5 years. A placebo-controlled design was used to measure three neuroendocrine hormones (prolactin, cortisol and growth hormone) following a challenge with the central serotonergic agonist m-chlorophenylpiperazine (mCPP). Infusion of mCPP resulted in augmented prolactin, cortisol and growth hormone release. Gender effects were significant for prolactin, cortisol and growth hormone. Females had higher baseline prolactin without significant interactions with infusion or time, cortisol levels were higher in males than in females at all time points without significant interactions with infusion or time, and the augmented growth hormone response to mCPP was limited to males. Systolic and diastolic blood pressure, heart rate and temperature were all mildly elevated following mCPP infusion. Side effects to mCPP infusion were mild and lasted approximately 20 min. We conclude that mCPP is useful in the study of serotonergic neuroendocrine hormones in adolescents, is well tolerated, and the levels of prolactin, cortisol and growth hormone are influenced by gender.

Although several studies have investigated the occurrence of medical and neurological conditions in persons with autism, relatively few reports have focused on the phenomenology and treatment of psychiatric disorders in this population. There is emerging evidence that depression is probably the most common psychiatric disorder that occurs in autistic persons. In this review, we examine the factors that influence the presence of depression in this population, such as the level of intelligence, age, gender, associated medical conditions, and the role of genetic factors and life events. We discuss the various forms of treatment available and highlight the need for early detection.

Depression is a ubiquitous disorder in childbearing women with up to 10% of women experiencing depression in pregnancy. Postpartum depression occurs in 12-16% of pregnancies making it a common complication. Moreover, these illnesses are frequently underdiagnosed in obstetric settings, and a recent report of the Surgeon General's Office confirms that many women do not access services, or receive treatment of inadequate intensity or duration. This paper provides current treatment guidelines to aid in appropriate diagnosis and treatment of depression in pregnancy and postpartum. Review of current literature on psychotropic medication use in pregnancy is also provided.

The conflicts in Afghanistan and Iraq have greatly increased the number of veterans returning home with combat exposure, reintegration issues, and psychiatric symptoms. National Guard soldiers face additional challenges. Unlike active duty soldiers, they do not return to military installations with access to military health services or peers. The authors describe the formation and activities of a partnership among two large state universities in Michigan and the Michigan Army National Guard, established to assess and develop programming to meet the needs of returning soldiers. The process of forming the partnership and the challenges, opportunities, and benefits arising from it are described.

This study examined central serotonin disturbance, as reflected by neuroendocrine hormones, among adolescents with major depression. Prolactin, cortisol, and growth hormone were measured following the infusion of a serotonin agonist, meta -chlorophenylpiperazine ( m CPP). Twelve (M=6, F=6) medication-free adolescents with major depression (MDD) were compared with 12 (M=6, F=6) matched normal control subjects, ranging in age from 13 to 17 years. Baseline evaluations and a battery of laboratory tests were completed. m CPP, 0.1 mg/kg i.v., was administered in a placebo-controlled design. Analyses of the neuroendocrine hormones revealed that the depressed group had a higher baseline prolactin level and an augmented prolactin response to m CPP challenge than did the control group. The depressed group experienced a sharper baseline-cortisol decline between 08.00 and 11.00 h, and compared to control subjects they displayed an augmented response to the challenge. The depressed group reported more side effects than the control group during saline infusion, but not during m CPP infusion. Findings suggest that depressed adolescents have an elevated baseline prolactin level, and also experience enhanced prolactin and cortisol responses to the serotonergic challenge. These preliminary findings will be confirmed during our ongoing study.

Unipolar and bipolar depression are episodic, recurrent illnesses for the majority of patients. Because each episode engenders considerable costs for patients, families, and society, prevention of recurrences has high priority. Numerous studies demonstrate that maintenance antidepressants or mood stabilizing medications are efficacious in preventing recurrences. A review of maintenance studies supports the view that all antidepressants perform significantly better than placebo in preventing recurrences of depression--with the stipulation that full antidepressant doses be employed. Earliest studies, conducted two decades ago, evaluated tricyclics (TCAs), heterocyclics, and lithium, while recent studies have focused on selective serotonin reuptake inhibitors (SSRIs). Compliance is essential. Strategies for enhancing compliance include selection of medications with reported safety and few side effects, education of patients and families, referral to patient advocacy groups, and use of new technological compliance aids. Preliminary data suggest that SSRIs are better tolerated than TCAs; fewer patients discontinue these agents due to side effects. Selection criteria for maintenance treatment have not been well determined, but three or more prior episodes is recognized as a relatively strong indicator. Other clinical or genetic criteria have also been suggested. For various reasons, patients may discontinue medications, and when this happens withdrawal phenomena may occur. Withdrawal effects are well documented for all antidepressants and can be profound with TCAs. After stopping some SSRIs, a few withdrawal symptoms may have similarities with those following discontinuation of TCAs, but unique "CNS-like" effects are frequently described, including brief recurrent episodes of dizziness, lightheadedness, vertigo, electric shock-like sensations, and gait instability. These appear to be half-life dependent, with agents with shorter half-lives having more discontinuation symptoms. If antidepressant medications must be discontinued, a gradual taper is preferable, perhaps extending three to six months or longer to prevent discontinuation effects, enable adaptation at the receptor level and allow earlier recognition and treatment of recurrent depressive symptoms.

Limited information is available about the occurrence of depression in children with autism and other pervasive developmental disorders (PDD). Although depression has been described in autistic children, questions about its validity have often been raised. One approach to address this issue is to investigate family histories of those autistic children diagnosed with clinical depression. Based on data available in nonautistic children, autistic children with depression would be expected to show an increased family history of depression. Since studies of this nature have not been attempted in autistic children, we compared the family history of 13 autistic/PDD children with depression (11 male; 2 female; M full-scale IQ 86.2, SD 24.2; M age 10.4 years, SD 2.2) with 10 autistic/PDD children without a history of current or previous depression (9 male; 1 female; M full-scale IQ 67, SD 12.9; M age 10.5 years, SD 1.6). Diagnosis of depression was based on the DSM-III-R criteria and confirmed independently by two psychiatrists. Ten (77%) of the depressed children had a positive family history of depression compared to 3 (30%) of the nondepressed group, t(21)=-2.4; p=.02. These findings lend support to the validity of depression as a distinct condition in some children with autism/PDD and suggest that, as in the normal population, autistic children who suffer from depression are more likely to have a family history of depression.

The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.

Depression prevalence was examined by race/ethnicity in a nationally representative sample. The Diagnostic Interview Schedule was administered to 8449 (response rate=96.1%) participants (aged 15–40 years). Prevalence of major depressive disorder was significantly higher in Whites than in African Americans and Mexican Americans; the opposite pattern was found for dysthymic disorder. Across racial/ethnic groups, poverty was a significant risk factor for major depressive disorder, but significant interactions occurred between race/ethnicity, gender, and education in relation to prevalence of dysthymic disorder.

By coming together as a national, interdisciplinary, collaborative community of mental health, we have the potential to realize major gains against mental illnesses laid out by President Kennedy in 1963.

A study was conducted to compare the relative efficacy of fluoxetine and phenelzine in patients with mood-reactive atypical depression. Forty-two patients with atypical depression by the Columbia criteria were studied in a randomized, double-blind treatment study. Following a single-blind placebo lead-in, patients received fluoxetine 20-60 mg/day or phenelzine 45-90 mg/day for 6 weeks. Efficacy was measured by the Hamilton Depression Rating Scale, the Clinical Global Impression (Severity and Improvement) scales, and the Patient Global Impression (Improvement) scale. Of 42 patients randomized, 2 patients never received drugs and 2 phenelzine-treated patients dropped out prior to completion; the remainder completed the 6 weeks of the study. The rates of treatment response did not differ between groups. With a few exceptions (e.g., tremor), phenelzine produced more frequent adverse effects than fluoxetine. It was concluded that fluoxetine is as effective as phenelzine in the treatment of atypical depression, but produces fewer adverse effects and is better tolerated.