Pharmacogenomic testing for mental health (Part I): documenting early adopter perceptions of use for eight scenarios.

Aim: We sought to understand how early adopters used pharmacogenomic (PGx) testing for treating depression and attention deficient hyperactivity disorder (ADHD). Patients & methods: We conducted a phone survey with prescribers who had previously ordered an Informed PGx (Progenity, Inc., MI, USA) test. Results: We identified 1037 prescribers in our sampling period. Respondents (n = 64) were predominantly female (61.5%) and in pediatrics (n = 42; 64.6%). PGx testing was used for multiple scenarios (mean 3.3 ± 1.6); the most common was after no response to medication was observed (80%; 51/64). Most respondents state that test results typically reveal an altered metabolizer status. Conclusion: PGx test results ordered by early adopters often reveal altered metabolizers which leads them to change the depression/ADHD medication regimen. Future work should evaluate the clinical utility of PGx testing for depression/ADHD treatment.

Pharmacogenomic testing for mental health (Part II): qualitative analysis of early adopter prescriber perceptions.

Aim: We sought to explore how early adopters use pharmacogenomic (PGx) testing for treating depression and attention-deficit/hyperactivity disorder. Patients & methods: Prescribers of the Informed PGx (Progenity, Inc., Ann Arbor, MI 48108, USA) test completed a phone survey assessing use of PGx testing for different scenarios. We conducted a qualitative thematic text analysis of transcribed audio recordings of open-ended responses (n = 62). Results: PGx testing was used when treating multiple comorbidities or resistant disease, and to ease patients' concerns with future therapy. Use of PGx testing is influenced by insurance coverage, interpretability of results and results turnaround time. Conclusion: Prescribers used PGx tests to modify medications for complex patients with depression, attention-deficit/hyperactivity disorder and other disorders to alleviate concerns related to adverse effects and lack of effectiveness.

Long-term clinical outcomes of care management for chronically depressed primary care patients: a report from the depression in primary care project.

PURPOSE: Recent studies examining depression disease management report improvements in short-term outcomes, but less is known about whether improvements are sustainable over time. This study evaluated the sustained clinical effectiveness of low-intensity depression disease management in chronically depressed patients. METHODS: The Depression in Primary Care (DPC) intervention was introduced in 5 primary care practices in the University of Michigan Health System, with 5 matched practices selected as control sites. Clinicians were free to refer none, some, or all of their depressed patients at their discretion. Core clinical outcomes of remission and serial change in Patient Health Questionnaire (PHQ-8) scores for 728 DPC enrollees observed for up to 18 months after enrollment were compared with those for 78 patients receiving usual care who completed mailed questionnaires at baseline, 6, 12, and 18 months. RESULTS: DPC enrollees had sustained improvement in remission rates and reduced-function days over the full 18 months. Mean change in the PHQ-8 score over each 6-month interval was more favorable for DPC enrollees than for usual care patients, and the proportion of DPC enrollees in remission was higher at 6 months (43.4% vs 33.3%; P = .11), 12 months (52.0% vs 33.9%; P = .012), and 18 months (49.2% vs 27.3%; P = .004). Multivariate analysis controlling for age, sex, ethnicity, baseline severity, and comorbid medical illness confirmed that DPC enrollees had significantly more reduction in depressive symptom burden over 18 months. CONCLUSIONS: The DPC intervention produced sustained improvement in clinical outcomes over 18 months in a cohort of chronically depressed patients with persistent symptoms despite active treatment.

Using Pharmacogenomic Testing in Primary Care: Protocol for a Pilot Randomized Controlled Study.

BACKGROUND: Antidepressants are used by primary care providers to treat a variety of conditions, including (but not limited to) depression and anxiety. A trial-and-error approach is typically used to identify effective therapy, as treatment efficacy and safety can vary based on the response, which is affected by certain gene types. Pharmacokinetic pharmacogenomic (PGx) testing provides phenotypic classification of individuals as poor, intermediate, extensive, and ultrarapid CYP450 metabolizers, providing information for optimal drug selection. OBJECTIVE: The objective of this pilot study is to examine the feasibility, acceptability, and preliminary effectiveness of PGx testing when used after starting a new antidepressant medication. METHODS: We are conducting a pilot study with physicians from 6 Department of Family Medicine clinics at the University of Michigan who are willing to use PGx test results to manage antidepressant medication use. From enrolled physicians, patients were recruited to participate in a 6-month randomized, wait-list controlled trial in which patient participants newly prescribed an antidepressant had PGx testing and were randomized equally to have the results released to their primary care physician as soon as results were available or after 3 months. Patients were excluded if they had been taking the antidepressant for more than 4 weeks or if they had undergone PGx testing in the past. Physician participants completed a baseline survey to assess demographics, as well as knowledge, feasibility, and acceptability of PGx testing for this population. At the conclusion of the study, physician participants will complete a survey to assess knowledge, satisfaction, feasibility, acceptability, perceived effectiveness, and barriers to widespread adoption of PGx testing. Patient participants will complete a baseline, 3-month, and 6-month assessment, and control patient participants will have an additional 9-month assessment. Data collected will include the reason for antidepressant use, self-reported medication adherence, side effects, patient health questionnaire 8-item depression scale, generalized anxiety disorder 7-item scale, 12-Item Short-Form Health Survey, work status or changes, and physician and emergency department visits. PGx knowledge and perceptions (including acceptability and feasibility) as well as demographic information will also be obtained. RESULTS: We recruited 23 physician participants between November 2017 and January 2019, and 52 patient participants between January 2018 and April 2019. Currently, all physician and patient participants have been recruited, and we expect data collection to conclude in January 2020. CONCLUSIONS: This study will examine the preliminary effectiveness of PGx testing after treatment initiation and determine the feasibility and acceptability of PGx testing for use in primary care. Through this study, we expect to demonstrate the benefit of PGx testing and lay the foundation for translating this approach into use within primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03270891; https://clinicaltrials.gov/ct2/show/NCT03270891. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/13848.

Impact of a generalizable reminder system on colorectal cancer screening in diverse primary care practices: a report from the prompting and reminding at encounters for prevention project.

BACKGROUND: Computerized reminder systems (CRS) show promise for increasing preventive services such as colorectal cancer (CRC) screening. However, prior research has not evaluated a generalizable CRS across diverse, community primary care practices. We evaluated whether a generalizable CRS, ClinfoTracker, could improve screening rates for CRC in diverse primary care practices. METHODS: The study was a prospective trial to evaluate ClinfoTracker using historical control data in 12 Great Lakes Research In Practice Network community-based, primary care practices distributed from Southeast to Upper Peninsula Michigan. Our outcome measures were pre- and post-study practice-level CRC screening rates among patients seen during the 9-month study period. Ability to maintain the CRS was measured by days of reminder printing. Field notes were used to examine each practice's cohesion and technology capabilities. RESULTS: All but one practice increased their CRC screening rates, ranging from 3.3% to 16.8% improvement. t tests adjusted for within practice correlation showed improvement in screening rates across all 12 practices, from 41.7% to 50.9%, P = 0.002. Technology capabilities impacted printing days (74% for high technology vs. 45% for low technology practices, P = 0.01), and cohesion demonstrated an impact trend for screening (15.3% rate change for high cohesion vs. 7.9% for low cohesion practices). CONCLUSIONS: Implementing a generalizable CRS in diverse primary care practices yielded significant improvements in CRC screening rates. Technology capabilities are important in maintaining the system, but practice cohesion may have a greater influence on screening rates. This work has important implications for practices implementing reminder systems.

Explaining patients' beliefs about the necessity and harmfulness of antidepressants.

PURPOSE: Patients' beliefs about antidepressants vary widely and probably influence adherence, yet little is known about what underlies such beliefs. This study's objective was to identify the demographic and clinical characteristics that account for patients' beliefs about antidepressants. METHODS: Participants were 165 patients with unipolar nonpsychotic major depression from primary care and psychiatry clinics who were participating in the baseline phase of a multistaged trial of medication and psychotherapy. Before patients started antidepressants, interview and self-report measures were used to assess treatment beliefs, depression features, and comorbid conditions. Linear multivariate regression was used to identify the strongest correlates of perceived medication necessity and harmfulness after adjusting for age, sex, education, and the random effects of patients within clinical site. RESULTS: Perceived necessity was associated with older age (P <.001), more severe symptoms (P = .03), longer anticipated duration of symptoms (P=.001), and attribution of symptoms to chemical imbalance (P=.005). Perceived harmfulness was highest among patients who had not taken antidepressants before (P = .02), attributed their symptoms to random factors (P=.04), and had a subjectively unclear understanding of depression (P = .003). Neither belief was significantly associated with sex, education, age at first depressive episode, presence of melancholia or anxiety, psychiatric comorbidity, or clinical setting. CONCLUSIONS: Skepticism about antidepressants is strongest among younger patients who have never taken antidepressants, view their symptoms as mild and transient, and feel unclear about the factors affecting their depression. Perhaps these patients would benefit the most from adherence promotion focusing on treatment beliefs.

Trajectories of improvement for six depression-related outcomes.

OBJECTIVE: Although depression treatment improves diverse outcomes, it is unclear whether these improvements are comparable in magnitude and timing. The objective was therefore to compare treatment-related improvements in depressive symptoms, work and social functioning, hopefulness, somatic complaints and positive well-being. METHOD: Secondary analysis of a large clinical trial of selective serotonin reuptake inhibitors for primary care depression. Depressed patients (n=573) from 37 practices from two primary care networks were randomized to fluoxetine, paroxetine or sertraline, and then followed naturalistically. At 1, 3, 6 and 9 months after treatment initiation, assessments were made of depressive symptom severity, social and work functioning, positive well-being, hopefulness beliefs and somatic complaints. Data were analyzed with linear regression modeling. RESULTS: Although 68% and 88% of total mood improvement occurred by Months 1 and 3, respectively, improvement plateaued sooner for somatic complaints (P=.001 at Month 1), and more gradually for hopefulness [P (Month 1)=.015, P (Month 3)=.036]. Although magnitude of improvement was interrelated across outcomes, timing of mood improvement was unrelated to the timing of improvement in both somatic complaints and hopefulness. Improvement in somatic complaints was primarily attributable to improvements in head, back and stomach pain. CONCLUSIONS: Work and social functioning, and positive affect improve synchronously with mood. Compared to mood, improvement in pain complaints peaks earlier, whereas improvement in hopefulness is much more linear over time. Because depression treatment response appears to be complex and multidimensional, a broader conceptualization of depression remission may be indicated.

Adherence to maintenance-phase antidepressant medication as a function of patient beliefs about medication.

PURPOSE: This study aimed to identify the demographic, psychiatric, and attitudinal predictors of treatment adherence during the maintenance phase of antidepressant treatment, ie, after symptoms and regimen are stabilized. METHODS: We surveyed 81 primary care patients given maintenance antidepressant medications regarding general adherence, recent missed doses, depression and treatment features, medication beliefs (necessity, concerns, harmfulness, and overprescription), and other variables. Additional data were collected from medical and payer records. RESULTS: Median treatment duration was 75 weeks. Adherence and beliefs were broadly dispersed and unrelated to treatment duration and type, physical functioning, and demographics. Multivariate analysis adjusting for social desirability, depression severity, and treatment duration indicated that an antidepressant-specific "necessity-minus-concerns" composite was strongly associated with both adherence outcomes. Specifically, adherence was highest when necessity exceeded concerns and lowest when concerns exceeded necessity. We crossed these 2 dimensions to characterize 4 patient attitudes toward antidepressants: skepticism, indifference, ambivalence, and acceptance. CONCLUSIONS: Patients given maintenance antidepressants vary widely in adherence. This variation is primarily explained by the balance between their perceptions of need and harmfulness of antidepressant medication, in that adherence is lowest when perceived harm exceeds perceived need, and highest when perceived need exceeds perceived harm. We speculate on ways to tailor adherence strategies to patient beliefs. Subsequent research should determine whether patients' perceptions about medication predict depression outcomes, can be used to improve clinical management, and respond to behavioral intervention.

Clinical reminders designed and implemented using cognitive and organizational science principles decrease reminder fatigue.

BACKGROUND: Response rates to point-of-care clinical reminders typically decrease over time. We hypothesized that this "reminder fatigue" could be prevented by (1) applying sound human factors engineering and cognitive science principles in designing the reminder system, and (2) implementing the reminders with rigorous attention to organizational science principles. METHODS: This was a retrospective cohort enumeration from January 1, 2006, through July 31, 2012, in a set of 5 academically affiliated family medicine practices. We modeled the odds ratio of clinician action in response to a reminder according to the number of reminders issued during the encounter, the number of problems on the patient's problem list, patient age, and time (number of months since launch) using logistic regression with clustering by encounter. RESULTS: There were issued 988,149 reminders at 453,537 encounters during the sampling frame. Action was taken in response to 60.1% of reminders, and discussion or consideration was documented in another 26.8%. The odds ratios for action in response to reminders over time, by number of prompts during the encounter, and by number of problems were 1.01, 1.18, and 1.02, respectively. Key design features included issuing reminders only when a service was due, allowing clinicians to attend to reminders when doing so fit their workflow (vs forcing attention at a specific time), keeping reminders very short and simple (action item only, no explicative material), and a team meeting and buy-in process before each new reminder was implemented. CONCLUSIONS: Reminder fatigue over time, with increasing numbers of reminders and with increasing complexity of patients, is not inevitable. A reminder system designed and implemented in accordance with the principles of cognitive science and human factors engineering can prevent reminder fatigue.

Improving the assessment of depression remission with the Remission Evaluation and Mood Inventory Tool.

OBJECTIVE: The Remission Evaluation and Mood Inventory Tool (REMIT) is a practical 5-item self-report measure of key positive mood states associated with recovering from depression, as distinct from depressive symptoms per se. The study goal was to identify a clinically useful threshold for interpreting REMIT responses in the context of mild to moderate depressive symptoms. METHODS: This was a secondary analysis of a cross-sectional dataset initially used to develop and validate the REMIT. Primary care patients being treated for depressive symptoms of either mild or moderate severity (n = 247 and 240, respectively) rated their perceived degree of depression remission prior to completing the Patient Health Questionnaire-8 (PHQ-8) and the REMIT. We summed the totals of the latter two measures to form the PHQ + REMIT index. RESULTS: Receiver Operating Characteristics analysis indicated that the PHQ + REMIT threshold ≥ 13 was associated with good sensitivity (92%) and acceptable specificity (43%) to the absence of patient-perceived remission. In contrast, the PHQ had only 21% specificity at this sensitivity level. Area under the curve was 0.815 (95% C.I.: 0.765-0.865), which was significantly greater than that of the PHQ-8 alone (area under the curve = 0.745, 95% C.I.: 0.691-0.805, p(diff) = 0.0002). Threshold performance was unaffected by adjustment for demographic characteristics and variation in remission percentage. Compared with standard symptom-based classification, using the REMIT reclassified 27% of mildly symptomatic patients as remitted. CONCLUSIONS: Using the REMIT with patients who have mild to moderate depressive symptoms improves the assessment of patient-perceived remission, which is indicated by a summed PHQ + REMIT index of less than 13. Longitudinal research is needed to test whether this broadened patient-centered approach to assessing remission improves clinical decision making and long-term outcomes.

Health information technology needs help from primary care researchers.

While health information technology (HIT) efforts are beginning to yield measurable clinical benefits, more is needed to meet the needs of patients and clinicians. Primary care researchers are uniquely positioned to inform the evidence-based design and use of technology. Research strategies to ensure success include engaging patient and clinician stakeholders, working with existing practice-based research networks, and using established methods from other fields such as human factors engineering and implementation science. Policies are needed to help support primary care researchers in evaluating and implementing HIT into everyday practice, including expanded research funding, strengthened partnerships with vendors, open access to information systems, and support for the Primary Care Extension Program. Through these efforts, the goal of improved outcomes through HIT can be achieved.

The role of algorithms in the detection and treatment of depression in primary care.

Many depressed patients present to primary care physicians instead of psychiatrists, and several studies have found that primary care physicians underdiagnose and undertreat depression. Primary care physicians may fail to diagnose and treat depression for many reasons: depression as it appears in primary care is in many ways a different disease than that seen in the psychiatric setting, and the process of detecting and treating it is different as well. Primary care clinicians face 2 main tasks when addressing depression in routine practice: to accurately identify those patients who are most likely to benefit from antidepressant treatment and to provide the best treatment options possible in the limited time available per visit. Treatment algorithms can be useful, but they are often difficult to apply in primary care. This article reviews the evidence about the detection and treatment of depression in primary care, examines current research on the differences between the primary and specialty care environments, and discusses aspects of treatment guidelines and algorithms that are important to primary care physicians.

Emotional disorders in primary care.

Individuals with emotional disorders are more likely to use primary medical care than specialty mental health services, but these disorders are likely to be undetected or inadequately treated. Recognition of the importance of primary medical care for the treatment of mental disorder has resulted in pressing new research priorities. One set of issues concerns the adequacy of existing nosological systems for conceptualizing emotional disorder in primary care and identifying need for treatment. Another concerns the difficulties translating efficacious treatment into effective strategies that can be integrated into the competing demands of primary medical care. Psychologists have played only a limited role in defining and addressing emerging questions. Irreversible changes in mental health services have created the need for the development of a psychosocial perspective for what would otherwise be defined as narrowly biomedical issues.

Improved detection of depression in primary care through severity evaluation.

OBJECTIVES: To determine whether the use of a symptom severity measure to augment an existing Diagnostic and Statistical Manual of Mental Disorders-Third Edition, Revised (DSM-III-R) criteria-based depression screener (PRIME-MD) would decrease the difficulties associated with depression screening in primary care by filtering out patients with minimal impairment. STUDY DESIGN: The study design was secondary data analysis. POPULATION: The study sample comprised 1317 patients, with intentional oversampling by ethnicity and sex, presenting for routine care at a university family practice center in Galveston, Texas. OUTCOMES MEASURED: The primary outcomes were cross-sectional, health-related quality-of-life outcomes of subjects who met symptom severity criteria as well as criteria for a DSM-III-R mood disorder. Health care utilization outcomes were examined as secondary outcomes. RESULTS: The combination of a 6-item depression severity instrument and the PRIME-MD resulted in 71% of depressed subjects being categorized as severely symptomatic and 29% as minimally symptomatic. Severely symptomatic subjects had significantly worse SF-36 Mental Health Component Summary scale (MCS) scores than did minimally symptomatic subjects (32.8 vs 43.5, P <.05). Minimally symptomatic subjects had MCS scores similar to those of a third group of subjects who did not meet DSM-III-R "threshold" criteria for mood disorder but who were severely symptomatic. Adjusted health care utilization was higher for the initial 3-month charge period in the severely symptomatic depressed subjects compared with minimally symptomatic depressed subjects ($679.20 vs $462.38, P <.05). CONCLUSIONS: The 6-item depression severity measure effectively separated patients meeting DSM-III-R "threshold" depression criteria into 2 groups: one presenting with severe symptoms and impairment and the other presenting with mild symptoms and significantly less impairment. A strategy of initial screening using a brief depression severity instrument, followed with a DSM criteria-based instrument, could decrease the immediate clinician workload by one third and focus treatment on those most likely to benefit.

Electronic health record functionality needed to better support primary care.

Electronic health records (EHRs) must support primary care clinicians and patients, yet many clinicians remain dissatisfied with their system. This article presents a consensus statement about gaps in current EHR functionality and needed enhancements to support primary care. The Institute of Medicine primary care attributes were used to define needs and meaningful use (MU) objectives to define EHR functionality. Current objectives remain focused on disease rather than the whole person, ignoring factors such as personal risks, behaviors, family structure, and occupational and environmental influences. Primary care needs EHRs to move beyond documentation to interpreting and tracking information over time, as well as patient-partnering activities, support for team-based care, population-management tools that deliver care, and reduced documentation burden. While stage 3 MU's focus on outcomes is laudable, enhanced functionality is still needed, including EHR modifications, expanded use of patient portals, seamless integration with external applications, and advancement of national infrastructure and policies.

Changes in patients' beliefs about their antidepressant during the acute phase of depression treatment.

PURPOSE: To test hypotheses regarding medication beliefs in relation to adherence, side effects, and response during the acute phase of an antidepressant treatment episode. METHODS: Participants were 163 patients with unipolar major depression participating in the acute phase of a multi-stage trial of medication and psychotherapy. Before starting citalopram, patients underwent measures of treatment beliefs and depression. They continued taking citalopram until either responding, discontinuing due to side effects, or failing to respond within 14 weeks. Assessments of adherence, side effects and depression were made at weeks 2, 4, 6, 9, 12 and 14 (as applicable) and at trial exit. Beliefs were reevaluated at exit. RESULTS: Perceived need for medication increased between baseline and exit (P=.01) while perceived medication harmfulness dropped between baseline and exit (P<.0001). Adherence was related to baseline perceived need (P=.022), and side effects were related to baseline perceived harmfulness (P=.002). Change in depressive symptoms was significantly related to both baseline perceived need (P=.039) and mean adherence (P=.036) but not baseline perceived harmfulness (P=.184) or side effects (P=.102). At exit, perceived need was unrelated to change in depression severity (P=.565), while perceived harmfulness was related to prior side effects (P<.0001). CONCLUSION: Patients' medication perceptions become more pro-adherence as treatment proceeds. Their perceptions of antidepressant necessity predict their subsequent medication adherence and response, while their perceptions about medication harmfulness show strong prospective associations with actual side effects. Clinicians ought to adjust their prescribing decisions accordingly. Interventions that target beliefs ought to capitalize upon the apparently bidirectional association between harm perceptions and actual side effects.

Using electronic health record-based tools to screen for bipolar disorder in primary care patients with depression.

PURPOSE: National guidelines recommend screening all persons with depression for bipolar disorder (BPD); one way to facilitate screening is through the use of electronic health records (EHRs). This study examined the impact of an EHR-based screening and decision support tool on diagnosis and treatment of BPD among patients diagnosed with depression in primary care offices. METHODS: This nonrandomized, controlled trial was conducted in a national network of offices using EHRs. The intervention included a screening instrument and other tools for diagnosis and management of BPD, which were embedded into the EHR. This instrument automatically activated when a patient with a diagnosis of depression but no diagnosis of BPD was seen in the office. The primary outcomes were the rates of new diagnoses of BPD and prescription of new BPD medications during the 6-month study period (April to October 2009). RESULTS: Twenty-one offices with 75 clinicians and 8355 adult patients with depression composed the intervention group, whereas 17 offices with 81 clinicians and 8799 adult patients with depression served as the comparison group. The screening tool was used with 47.5% of intervention patients, of whom 2.5% scored at high or very high risk for BPD. Intervention patients were more likely than comparison patients to be newly diagnosed with BPD (1.11% vs. 0.36%; P < .01) and be prescribed new BPD medications (1.85% vs. 1.19%; P < .01). CONCLUSIONS: The study suggests that EHR-based tools can be useful for screening and management of BPD for patients with depression in primary care offices.

Electronic clinical decision support for management of depression in primary care: a prospective cohort study.

OBJECTIVE: To assess the utility of an electronic clinical decision support tool for management of depression in primary care. METHOD: This prospective study was conducted in a national network of ambulatory practices over a 1-year period (October 2007-October 2008). A clinical decision support tool was embedded into the electronic health record of 19 primary care practices with 119 providers. The main components included (1) the 9-item Patient Health Questionnaire (PHQ-9), with 9 questions paralleling the 9 DSM-IV criteria for the diagnosis of major depressive disorder; (2) a suicide assessment form; and (3) brief patient and provider education. Use of each component was tracked in the electronic health record. Providers completed baseline and postintervention surveys regarding their depression management practices and their perceptions of the clinical decision support tool. RESULTS: According to electronic health record tracking, the PHQ-9 form was used in 45.6% of the 16,052 adult patients with depression and in 73.7% of the 1,422 patients with new depression. The suicide assessment form was used in 62.0% of patients with possible suicidality. Education modules were rarely used. From before to after the study, providers reported increased use of standardized tools for depression diagnosis (47% to 80%, P < .001) and monitoring (27% to 85%, P < .001). The majority of providers reported often using the PHQ-9 and suicide forms and felt them to be very helpful in patient care, with 85% planning to continue their use after the study. CONCLUSIONS: The electronic health record-based clinical decision support tool was extensively used and perceived as very helpful for assessment of patients' symptoms but not for provider education. These findings can help guide national efforts incorporating clinical decision support for quality improvement.