Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions.

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

Texas Youth Depression and Suicide Research Network (TX-YDSRN) research registry and learning healthcare network: Rationale, design, and baseline characteristics.

BACKGROUND: American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants. METHODS: TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality symptoms, associated comorbidities, treatment history, services used, and social determinants of health. Subsequent assessments occur every two months for 24 months. RESULTS: Among 1000 participants, 68.7 % were 12-17 years, 24.6 % were ≥ 18 years, and 6.7 % were < 12. Overall, 36.8 % were non-Hispanic Caucasian, 73.4 % were female, and 79.9 % had a primary depressive disorder. Nearly half of the sample reported ≥1 suicide attempt, with rates similar in youth 12-17 years old (49.9 %) and those 18 years and older (45.5 %); 29.9 % of children <12 reported at least one suicide attempt. Depression and anxiety scores were in the moderate-severe range for all age groups (Patient Health Questionnaire for Adolescents [PHQ-A]: 12.9 ± 6.4; Generalized Anxiety Disorder [GAD-7]: 11.3 ± 5.9). LIMITATIONS: The sample includes youth who are receiving depression care at enrollment and may not be representative of non-diagnosed, non-treatment seeking youth. CONCLUSIONS: The TX-YDSRN is one of the largest prospective longitudinal cohort registries designed to develop predictive models for outcome trajectories based on disorder heterogeneity, social determinants of health, and treatment availability.

Psychometrics of the Concise Health Risk Tracking Self-Report (CHRT-SR16) Assessment of Suicidality in a Sample of Adults with Moderate to Severe Methamphetamine Use Disorder: Findings from the ADAPT-2 Randomized Trial.

Background: The co-occurrence of suicidality and substance use disorders has been well established, but rating scales to examine suicidal behavior and risk are sparse among participants with substance use disorders. We examined the psychometric properties of the 16-item Concise Health Risk Tracking Scale - Self Report (CHRT-SR16) to measure suicidality among adults with moderate-to-severe methamphetamine use disorder. Methods: Participants (n = 403) with moderate-to-severe methamphetamine use disorder completed the CHRT-SR16 as part of a randomized, double-blind, placebo-controlled pharmacotherapy trial. The CHRT-SR16 factor structure was assessed using confirmatory factor analysis (CFA). Internal consistency was estimated with coefficients alpha (α) and omega (ω), test-retest reliability with intraclass correlation coefficient (ICC) and standard error of measurement, and convergent validity using Spearman's ρ rank order correlation coefficient test between CHRT-SR16 factors and the Patient Health Questionnaire (PHQ-9). The analyses utilized baseline and week 1 data (for test-retest reliability only). Results: CFA revealed a seven-factor model of Pessimism, Helplessness, Social Support, Despair, Impulsivity, Irritability, and Suicidal Thoughts as the best-fitting model. The CHRT-SR16 also exhibited strong internal consistency (α = 0.89; ω = 0.89), test-retest reliability (ICC = 0.78) and convergent validity with the PHQ-9 total score (ρ = 0.62). Conclusion: The CHRT-SR16 showed strong psychometric properties in a sample of participants with primary methamphetamine use disorder. Clinicaltrialsgov Identifier: NCT03078075.

Suicide risk assessment and suicide risk management protocol for the Texas Youth Depression and Suicide Research Network.

Introduction: Suicide prevention research is a national priority, and national guidance includes the development of suicide risk management protocols (SRMPs) for the assessment and management of suicidal ideation and behavior in research trials. Few published studies describe how researchers develop and implement SRMPs or articulate what constitutes an acceptable and effective SRMP. Methods: The Texas Youth Depression and Suicide Research Network (TX-YDSRN) was developed with the goal of evaluating screening and measurement-based care in Texas youth with depression or suicidality (i.e., suicidal ideation and/or suicidal behavior). The SRMP was developed for TX-YDSRN through a collaborative, iterative process, consistent with a Learning Healthcare System model. Results: The final SMRP included training, educational resources for research staff, educational resources for research participants, risk assessment and management strategies, and clinical and research oversight. Conclusion: The TX-YDSRN SRMP is one methodology for addressing youth participant suicide risk. The development and testing of standard methodologies with a focus on participant safety is an important next step to further the field of suicide prevention research.

Psychometric properties of the Treatment Effectiveness Assessment in methamphetamine use disorder.

INTRODUCTION: The ability for people living with stimulant use disorder to live meaningful lives requires not only abstinence from addictive substances, but also healthy engagement with their community, lifestyle practices, and overall health. The Treatment Effectiveness Assessment (TEA) assesses components of recovery consisting of four functional domains: substance use, health, lifestyle, and community. This secondary data analysis of 403 participants with severe methamphetamine use disorder tested the reliability and validity of the TEA. METHODS: Participants were enrolled in the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for methamphetamine use disorder. The study used total TEA and domain scores at baseline to assess factor structure and internal consistency, as well as construct validity related to substance cravings (visual analog scale [VAS]), quality of life (quality-of-life assessment [QoL]), mental health (Patient Health Questionnaire-9 [PHQ-9], Concise Health Risk Tracking Scale Self-Report [CHRT-SR16]), and social support (CHRT-SR16). RESULTS: Individual TEA items showed moderate to large correlations with each other (r = 0.27-0.51; p < .001), and strong correlations to the total score (r = 0.69-0.78; p < .001). Internal consistency was strong (coefficient α = 0.73 [0.68-0.77]; coefficient ω = 0.73 [0.69-0.78]). Construct validity was acceptable, with the strongest correlation between the TEA Health item and the general health status item on the QoL (r = 0.53, p < .001). CONCLUSIONS: TEA has acceptable levels of reliability and validity supporting prior similar findings in a sample of participants with moderate to severe methamphetamine use disorder. Results from this study provide support for its use in assessing clinically meaningful changes beyond simply reduced substance use.

Profiles of depression in a treatment-seeking Hispanic population: Psychometric properties of the Patient Health Questionnaire-9.

OBJECTIVES: Screening instruments can be powerful tools in assisting primary care providers with detecting depression in their patients and monitoring treatment response. Health disparities among racial and ethnic minorities result from inaccurate assessment in primary care. METHODS: The current study used baseline data from two federally funded research studies of treatment for depression among Hispanics in primary care. The Patient Health Questionnaire-9 (PHQ-9) was administered at baseline prior to the study interventions, and 499 participants provided responses. RESULTS: Confirmatory factor analyses found excellent factor validity for the PHQ-9, yet reliability remained poor. Possible heterogeneity in depressive item scores was examined, and latent profile analysis identified four distinct profiles of PHQ-9 responses. Profiles included a lower depression, moderate/somatization, moderate/negative self-view, and severe depression profiles. Results indicate modest support for the PHQ-9 and its use among Hispanics for the purpose of depression screening. CONCLUSION: Capturing four profiles of depression in a large primary care sample helps characterize the manifestation of depression in a Hispanic population. The single item related to fatigue had the greatest variation across groups indicating it might be useful as a screening item. Inadequate evaluation of symptoms could lead to significant under identification of the disorder among Hispanics.

Culturally adapted depression education and engagement in treatment among Hispanics in primary care: outcomes from a pilot feasibility study.

BACKGROUND: Low use of anti-depressant medication, poor doctor-patient communication, and persistent stigma are key barriers to the treatment of depression in Hispanics. Common concerns include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking medications and seeking mental health treatments. In 2014, the Center for Medicare and Medicaid Services (CMS) funded the Depression Screening and Education: Options to Reduce Barriers to Treatment (DESEO) project to implement an education intervention designed to increase disease literacy and dispel myths about depression and its treatment among Hispanic patients thus reducing stigma and increasing treatment engagement. METHODS: The DESEO study utilized a one-group pretest-posttest design to assess the effects a culturally-adapted Depression Education Intervention's (DEI) on depression knowledge, stigma, and engagement in treatment in a sample of 350 Hispanic primary care patients with depression. The DEI utilized a fotonovela, a health education tool available in English and Spanish that uses posed photographs, captions, and soap opera narratives to raise awareness about depression and depression treatments. RESULTS: Participants reported significant decreases in depression symptoms and reported stigma about mental health care. Additionally, participants reported increased knowledge of depression yet greater negative perceptions about antidepressant medication. Finally, 89.5% of participants reported entering some form of treatment at follow-up. CONCLUSIONS: Culturally adapted depression education shows promise in increasing understanding of depression, decreasing stigma, and increasing treatment engagement among Hispanic patients in a community-based health center. Results have implications for practice in addressing common concerns about depression treatments which include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking psychotropic medications. TRIAL REGISTRATION: The study was retrospectively registered with www.clinicaltrials.gov : NCT02491034 July 2, 2015.

The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

BACKGROUND: Cocaine and methamphetamine have similar withdrawal symptoms and many individuals concurrently use both substances; however, no measures concurrently assess withdrawal from multiple stimulants. OBJECTIVES: This study's aim was to explore the Stimulant Selective Severity Assessment (SSSA), a modified version of the Cocaine Selective Severity Assessment (CSSA), in a sample of stimulant users to determine if it can assess withdrawal symptoms in users of one or more stimulants. METHODS: Baseline data were analyzed from the STimulant Reduction Intervention using Dosed Exercise trial, a multisite randomized clinical trial that evaluated exercise versus health education on drug use outcomes in individuals with stimulant use disorders. Data were analyzed for internal consistency, construct validity, and scale dimensionality. RESULTS: Internal consistency for the full sample was good (α = 0.81; N = 302), with similar alphas in Cocaine (0.81; n = 177) and Cocaine/Other Stimulant (0.82; n = 92) groups, but with much lower alpha for the group without cocaine use (Other Stimulant, i.e., primarily methamphetamine, α = 0.66; n = 32). Support for construct validity was evidenced by significant positive correlations (r = 0.17 to 0.67) with measures of stimulant craving, depressive symptoms, and pain. Four factors were revealed. Conclusions/Importance: The Stimulant Selective Severity Assessment is a new measure that can be used to assess withdrawal symptoms in users of cocaine or cocaine plus methamphetamine, but it should not be administered to users of methamphetamine only.

The Concise Health Risk Tracking Self-Report (CHRT-SR) assessment of suicidality in depressed outpatients: A psychometric evaluation.

BACKGROUND: The 12-item Concise Health Risk Tracking Self-Report (CHRT-SR12 ) is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. It can be used as a tool to both assess risk and guide treatment interventions targeting associated cognitions. METHODS: This report used acute treatment data from a clinically representative sample of outpatients with nonpsychotic major depressive disorder (N = 665) participating in the Combining Medications to Enhance Depression Outcomes trial, who received up to 12 weeks of escitalopram, escitalopram plus bupropion SR, or venlafaxine XR plus mirtazapine. Outcome assessors and patients were masked to treatment. RESULTS: Factor analysis of CHRT-SR12 confirmed that the 12 items have higher order structure with two subscales (Propensity, Suicidal Thoughts) and a total score. Internal consistencies were acceptable for both subscales and total score. All three scales were modestly correlated with overall depression severity (r = 0.54 to r = 0.21) and highly discriminating among patients grouped by suicide item ratings on three different depressive symptom ratings. The three scales also distinguished change over the acute phase treatment for those with different levels of baseline suicidal ideation (measured by 30-item Inventory of Depressive Symptomatology (item 18) and for those with change in suicidal ideation (baseline to last visit). CONCLUSIONS: The CHRT-SR12 has good to excellent psychometric properties and is sensitive to change in suicidal thinking and propensity toward suicidal behavior in outpatients with major depressive disorder. It allows for the monitoring of thoughts and feelings associated with increased suicidal risk as well as levels of thoughts about suicide.

Association of Midlife Cardiorespiratory Fitness With Incident Depression and Cardiovascular Death After Depression in Later Life.

Importance: Cardiorespiratory fitness (hereinafter referred to as fitness) as estimated by exercise testing is a modifiable risk factor independently associated with chronic diseases, cardiovascular disease (CVD) events, and mortality, but the association of fitness at midlife with incidence of later-life depression and the risk of CVD mortality after a depression diagnosis is unknown. Objective: To determine whether fitness measured in midlife would be inversely associated with later-life CVD mortality with antecedent depression. Design, Setting, and Participants: This retrospective cohort study at a single-center, community-based preventive medicine clinic was performed as part of the Cooper Center Longitudinal Study. Data were collected from January 13, 1971, through December 31, 2009, and analyzed from October 6, 2015, through August 14, 2017. Participants included generally healthy men and women who presented for preventive medicine examinations at midlife and who were eligible for Medicare from 1999 to 2010. Those with a self-reported history of depression, myocardial infarction, or stroke at examination were excluded. Exposures: Objective midlife fitness estimated from results of treadmill exercise testing. Main Outcomes and Measures: Depression diagnosis from Medicare claims files using established algorithms and CVD mortality from National Death Index records. Results: A total of 17 989 participants (80.2% men) with a mean (SD) age of 50.0 (8.7) years were included. After 117 218 person-years of Medicare follow-up, 2701 depression diagnoses, 610 deaths due to CVD without prior depression, and 231 deaths due to CVD after depression were observed. A high level of fitness in midlife was associated with a 16% lower risk of depression (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95) compared with a low level of fitness. A high fitness level was also associated with a 61% lower risk of death due to CVD without depression (HR, 0.39; 95% CI, 0.31-0.48) compared with a low level of fitness. After a diagnosis of depression, a high fitness level was associated with a 56% lower risk of death due to CVD (HR, 0.44; 95% CI, 0.31-0.64) compared with a low fitness level. Conclusions and Relevance: Midlife fitness is associated with a lower risk of later-life depression, CVD mortality, and CVD mortality after incident later-life depression. These findings suggest the importance of midlife fitness in primary prevention of depression and subsequent CVD mortality in older age and should encourage physicians to consider fitness and physical activity in promoting healthy aging.

Efficacy of a Behavioral Activation Teletherapy Intervention to Treat Depression and Anxiety in Primary Care VitalSign6 Program.

OBJECTIVE: Research analyzing behavioral activation (BA) teletherapy outcomes is limited. Among low-income real-world primary care patients receiving a brief BA teletherapy program for depression and anxiety, we analyzed descriptive statistics and changes in depression and anxiety scores throughout treatment. METHODS: One hundred thirty patients completed an intake assessment from June 2015 to August 2016; outcomes included the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7). Data from 74 low-income, primary care patients completing at least one therapy session were analyzed to characterize the demographics of therapy patients, to describe their depression and anxiety symptoms throughout treatment, and to examine whether patients who completed 4 or more sessions had statistically lower exit scores than those completing fewer than 4. RESULTS: Patients were moderately depressed (PHQ-9 score: mean = 14.46) and anxious (GAD-7 score: mean = 11.91) at intake. Patients were predominantly Latino/Latina (68.9%), Spanish-speaking (54.0%), and female (79.7%). The majority of patients who received at least one therapy session achieved and sustained depression remission. Patients who completed ≥ 4 therapy sessions demonstrated lower final session depression (PHQ-9: mean = 5.13, SD = 4.75) and anxiety (GAD-7: mean = 4.77, SD = 4.21) scores compared to those completing < 4 sessions (PHQ-9: mean = 8.04, SD = 6.20, P = .029; GAD-7: mean = 8.00, SD = 6.02, P = .011). CONCLUSIONS: Primary care patients demonstrated improvements in depressive and anxious symptoms throughout BA-based teletherapy. BA teletherapy is feasible and associated with improved outcomes as an adjunct or alternative intervention for primary care providers and in low-income, charity populations.​.

Measurement, Education and Tracking in Integrated Care (METRIC): use of a culturally adapted education tool versus standard education to increase engagement in depression treatment among Hispanic patients: study protocol for a randomized control trial.

BACKGROUND: Significant mental health disparities exist for Hispanic populations, especially with regard to depression treatment. Stigma and poor communication between patients and their providers result in low use of antidepressant medications and early treatment withdrawal. Cultural factors which influence treatment decisions among Hispanics include fears about the addictive and harmful properties of antidepressants, worries about taking too many pills, and the stigma attached to taking medications. Primary care settings often are the gateway to identifying undiagnosed or untreated mental health disorders, particularly for people with co-morbid physical health conditions. Hispanics, in particular, are more likely to receive mental healthcare in primary care settings. Recent recommendations from the U.S. Preventive Services Task Force are that primary care providers screen adult patients for depression only if systems are in place to ensure adequate treatment and follow-up. METHODS: We are conducting a randomized controlled trial among 150 depressed adult Hispanics in a primary care safety net setting, testing the effectiveness of a culturally appropriate depression education intervention to reduce stigma and increase uptake in depression treatment among Hispanics, and implement a Measurement-Based Integrated Care (MBIC) model with collaborative, multidisciplinary treatment and culturally tailored care management strategies. DISCUSSION: This study protocol represents the first randomized control trial of the culturally adapted depression education fotonovela, Secret Feelings, among Hispanics in a primary care setting. The education intervention will be implemented after diagnosis using an innovative screening technology and enrolled in measurement-based integrated care for the treatment of depression, which will help build the evidence around cultural adaptations in treatment to reduce mental health disparities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02702596. Registered on 20 March 2016.

Prognostic Utility of a Self-Reported Depression Questionnaire versus Clinician-Based Assessment on Renal Outcomes.

BACKGROUND: The prognostic utility of self-administered depression scales in chronic kidney disease (CKD) independent of a clinician-based major depressive disorder (MDD) diagnosis is neither clearly established nor are the optimal cutoff scores for predicting outcomes. The overlap between symptoms of depression and chronic disease raises the question of whether a cutoff score on a depression scale can be substituted for a time-consuming diagnostic interview to prognosticate risk. METHODS: The 16-item Quick Inventory of Depression Symptomatology-Self Report scale (QIDS-SR16) was administered to 266 consecutive outpatients with non-dialysis CKD, followed prospectively for 12 months for an apriori composite outcome of death or dialysis or hospitalization. Association of QIDS-SR16 best cutoff score, determined by receiver/responder operating characteristics curves, with outcomes was investigated using survival analysis. The effect modification of an interview-based clinician MDD diagnosis on this association was ascertained. RESULTS: There were 126 composite events. A QIDS-SR16 cutoff ≥8 had the best prognostic accuracy, hazards ratio (HR) = 1.77, 95% CI 1.24-2.53, p = 0.002. This cutoff remained significantly associated with outcomes even after controlling for comorbidities, estimated glomerular filtration rate, hemoglobin and serum albumin, adjusted HR (aHR) = 1.80, 95% CI 1.23-2.62, p = 0.002, and performed similarly to a clinician-based MDD diagnosis (aHR = 1.72, 95% CI 1.14-2.68). Adjustment for MDD conferred the association of QIDS-SR16 with outcomes no longer significant. CONCLUSIONS: QIDS-SR16 cutoff ≥8 adds to the prognostic information available to practicing nephrologists during routine clinic visits from comorbidities and laboratory data. This cutoff score performs similar to a clinician diagnosis of MDD and provides a feasible and time-saving alternative to an interview-based MDD diagnosis for determining prognosis in CKD patients.

Men and women from the STRIDE clinical trial: An assessment of stimulant abstinence symptom severity at residential treatment entry.

BACKGROUND AND OBJECTIVES: Gender-specific factors associated with stimulant abstinence severity were examined in a stimulant abusing or dependent residential treatment sample (N = 302). METHOD: Bivariate statistics tested gender differences in stimulant abstinence symptoms, measured by participant-reported experiences of early withdrawal. Multivariate linear regression examined gender and other predictors of stimulant abstinence symptom severity. RESULTS: Women compared to men reported greater stimulant abstinence symptom severity. Anxiety disorders and individual anxiety-related abstinence symptoms accounted for this difference. African American race/ethnicity was predictive of lower stimulant abstinence severity. DISCUSSION AND CONCLUSIONS: Women were more sensitive to anxiety-related stimulant withdrawal symptoms. SCIENTIFIC SIGNIFICANCE: Clinics that address anxiety-related abstinence symptoms, which more commonly occur in women, may improve treatment outcome.

Self-rated measure of pain frequency, intensity, and burden: psychometric properties of a new instrument for the assessment of pain.

BACKGROUND: A brief, self-administered measurement of pain frequency, intensity, and burden is desirable in both research and clinical settings. We describe the development and initial psychometric properties of a new instrument, the Pain Frequency, Intensity, and Burden Scale (P-FIBS). METHODS: The P-FIBS was administered to all participants (N = 302) with psychostimulant use disorders in the National Institute on Drug Abuse Clinical Trials Network's STRIDE (Stimulant Reduction Intervention using Dose Exercise) multisite trial. RESULTS: The four items on the P-FIBS demonstrate high item-total correlations (range 0.70-0.85) with a high Cronbach's alpha (0.90). The P-FIBS demonstrated a strong negative correlation with the bodily pain sub-score of the Short Form Health Survey (r = -0.76, p < 0.0001) and did not correlate with a measure of cocaine (r = 0.09, p = 0.12) or methamphetamine (r = -0.06, p = 0.33) craving. CONCLUSIONS: The P-FIBS demonstrates good psychometric properties. This brief measure can be used to assess pain in research settings or as a screen in clinical settings. Further research is needed to assess the measure's sensitivity to change with treatment.

Evaluating and monitoring treatment response in depression using measurement-based assessment and rating scales.

Even with many treatment options available for major depressive disorder, many patients fail to achieve remission and return to their presymptomatic levels of functioning at work, in leisure activities, and in relationships. Throughout treatment, clinicians should implement measurement-based care by systematically monitoring patients' response using self-rated scales, such as the PHQ-9, QIDS-SR, or BDI. By tracking depressive symptoms, as well as suicidality, treatment adherence, and side effects, clinicians can adjust treatment to help patients achieve the best outcomes. Measurement-based care enables clinicians to make informed decisions at critical points throughout the treatment process and to involve patients in making those decisions.

Effect of antidepressant medication treatment on suicidal ideation and behavior in a randomized trial: an exploratory report from the Combining Medications to Enhance Depression Outcomes Study.

OBJECTIVE: To explore relationships between baseline sociodemographic and clinical features and baseline suicidal ideation, and treatment effects on suicidal ideation and behavior, in depressed outpatients. METHOD: From March 2008 to September 2009, the Combining Medications to Enhance Depression Outcomes study, a single-blind, 7-month randomized trial, enrolled outpatients with nonpsychotic chronic and/or recurrent major depressive disorder (DSM-IV-TR criteria) in primary and psychiatric care (N = 665). Participants received escitalopram plus placebo, bupropion sustained release (SR) plus escitalopram, or venlafaxine extended release (XR) plus mirtazapine. The primary outcome measure for this report is presence of suicidal ideation assessed by the Concise Health Risk Tracking Self-Report, which measures suicidal ideation and behaviors over the last 24 hours. Sociodemographic and clinical features were compared in those with versus without baseline ideation. At 4, 12, and 28 weeks, treatment effects on suicidality were assessed, and unadjusted and adjusted outcomes were compared among those with and without baseline ideation using linear, logistic, ordinal logistic, and negative binomial regression models. RESULTS: Baseline suicidal ideation was associated with greater depressive severity, childhood neglect, childhood abuse, early major depressive disorder onset, greater psychiatric comorbidity, and worse functioning and quality of life. After adjustment for treatment, gender, age at first depressive episode, obsessive-compulsive symptoms, and depressive severity, depressive symptom outcomes did not differ between ideation groups at 12 or 28 weeks or between treatments. Overall, 79% of participants with baseline suicidal ideation had none at week 4, 83% had none at week 12, and 86% had none at week 28. All treatments reduced ideation, with bupropion-SR plus escitalopram the most effective at week 12 (P < .01). In participants without baseline ideation, emergent ideation did not differ between treatments: 2.5% had ideation at 4 weeks, 1.3% had ideation at 12 weeks, and only 1.7% had ideation at 28 weeks. Four patients (all receiving venlafaxine-XR plus mirtazapine) attempted suicide (P = .0162). CONCLUSION: Baseline ideation did not affect depressive symptom outcome. Bupropion-SR plus escitalopram most effectively reduced ideation. Ideation emergence was uncommon. Venlafaxine-XR plus mirtazapine may pose a higher risk of suicide attempts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00590863.

Power of automated algorithms for combining time-line follow-back and urine drug screening test results in stimulant-abuse clinical trials.

BACKGROUND: In clinical trials of treatment for stimulant abuse, researchers commonly record both Time-Line Follow-Back (TLFB) self-reports and urine drug screen (UDS) results. OBJECTIVES: To compare the power of self-report, qualitative (use vs. no use) UDS assessment, and various algorithms to generate self-report-UDS composite measures to detect treatment differences via t-test in simulated clinical trial data. METHODS: We performed Monte Carlo simulations patterned in part on real data to model self-report reliability, UDS errors, dropout, informatively missing UDS reports, incomplete adherence to a urine donation schedule, temporal correlation of drug use, number of days in the study period, number of patients per arm, and distribution of drug-use probabilities. Investigated algorithms include maximum likelihood and Bayesian estimates, self-report alone, UDS alone, and several simple modifications of self-report (referred to here as ELCON algorithms) which eliminate perceived contradictions between it and UDS. RESULTS: Among the algorithms investigated, simple ELCON algorithms gave rise to the most powerful t-tests to detect mean group differences in stimulant drug use. CONCLUSIONS: Further investigation is needed to determine if simple, naïve procedures such as the ELCON algorithms are optimal for comparing clinical study treatment arms. But researchers who currently require an automated algorithm in scenarios similar to those simulated for combining TLFB and UDS to test group differences in stimulant use should consider one of the ELCON algorithms. SCIENTIFIC SIGNIFICANCE: This analysis continues a line of inquiry which could determine how best to measure outpatient stimulant use in clinical trials (NIDA. NIDA Monograph-57: Self-Report Methods of Estimating Drug Abuse: Meeting Current Challenges to Validity. NTIS PB 88248083. Bethesda, MD: National Institutes of Health, 1985; NIDA. NIDA Research Monograph 73: Urine Testing for Drugs of Abuse. NTIS PB 89151971. Bethesda, MD: National Institutes of Health, 1987; NIDA. NIDA Research Monograph 167: The Validity of Self-Reported Drug Use: Improving the Accuracy of Survey Estimates. NTIS PB 97175889. GPO 017-024-01607-1. Bethesda, MD: National Institutes of Health, 1997).