Complexity of patients with mental healthcare needs cared for by mental health clinical pharmacist practitioners in Veterans Affairs.

PURPOSE: The complexity of patients with mental healthcare needs cared for by clinical pharmacists is not well delineated. We evaluated the complexity of patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD) in Veterans Affairs (VA) cared for by mental health clinical pharmacist practitioners (MH CPPs). METHODS: Patients at 42 VA sites with schizophrenia, bipolar disorder, or MDD in 2016 through 2019 were classified by MH CPP visits into those with 2 or more visits ("ongoing MH CPP care"), those with 1 visit ("consultative MH CPP care"), and those with no visits ("no MH CPP care"). Patient complexity for each condition was defined by medication regimen and service utilization. RESULTS: For schizophrenia, more patients in ongoing MH CPP care were complex than those with no MH CPP care, based on all measures examined: the number of primary medications (15.3% vs 8.1%), inpatient (13.7% vs 9.1%) and outpatient (42.6% vs 29.7%) utilization, and receipt of long-acting injectable antipsychotics (36.7% vs 25.8%) and clozapine (20.5% vs 9.5%). For bipolar disorder, more patients receiving ongoing or consultative MH CPP care were complex than those with no MH CPP care based on the number of primary medications (27.9% vs 30.5% vs 17.7%) and overlapping mood stabilizers (10.1% vs 11.6% vs 6.2%). For MDD, more patients receiving ongoing or consultative MH CPP care were complex based on the number of primary medications (36.8% vs 35.5% vs 29.2%) and augmentation of antidepressants (56.1% vs 54.4% vs 47.0%) than patients without MH CPP care. All comparisons were significant (P < 0.01). CONCLUSION: MH CPPs provide care for complex patients with schizophrenia, bipolar disorder, and MDD in VA.

Predicting suicidal ideation in psychiatrically hospitalized veterans using the death/suicide Implicit Association Test: A prospective cohort study.

INTRODUCTION: We investigated whether the Death/Suicide Implicit Association Test (D/S-IAT) predicted suicidal ideation (SI) in psychiatric inpatients. METHODS: One hundred eighty veterans admitted for either SI or suicidal behavior (SB) (the primary sample) (N = 90) or alcohol detoxification (N = 90) completed the D/S-IAT and scales measuring SI. Correlation and regression coefficients were measured between the D/S-IAT (as a full-scale or dichotomized score [D > 0]) and self-reported current or imminent SI (over the next 1-3 days). RESULTS: In the primary sample, the full-scale D/S-IAT was significantly correlated with the intensity of current SI (r = 0.22, p = 0.04) and especially with wishes to be dead (r = 0.35, p < 0.001). The intensity of imminent SI was significantly predicted by the full-scale (p = 0.02) and dichotomized D/S-IAT score (p = 0.05) in a multiple regression model. However, no significant associations were observed when both the D/S-IAT score and current (present/absent) or imminent SI (occurred/did not occur) were dichotomous measures. In participants receiving alcohol detoxification, the D/S-IAT significantly predicted only wishes to be dead (r = 0.33, p < 0.001). CONCLUSION: The full-scale D/S-IAT score predicted the current intensity of wishes to be dead in both inpatient samples, and current and imminent SI in participants admitted for SI/SB. The dichotomized D/S-IAT score did not predict the simple occurrence of SI.

A System for Rapidly Yet Rigorously Evaluating the Quality of Randomized Controlled Trials.

ABSTRACT: This tutorial describes a system for rapidly yet rigorously assessing the quality of randomized controlled trials (RCTs). The system has 7 criteria, represented by the acronym "BIS FOES." The BIS FOES system directs readers to assess RCTs based on the following 7 criteria: the RCT's use (or not) of effective (1) Blinding; the RCT's use (or not) of (2) Intent-to-Treat Analysis; the RCT's (3) Size and other information reflecting the effectiveness of randomization; the amount of sample lost during (4) Follow-up; the (5) Outcomes examined by the RCT (specifically, the outcome measures used by the RCT), the (6) Effects reported (ie, the statistical and clinical significance of the RCT's primary, secondary, and safety findings), and any (7) Special Considerations (ie, additional strengths, limitations, or notable features of the RCT). The first 6 criteria are of basic importance to the assessment of every RCT, whereas the Special Considerations criteria allows the system to be expanded to include virtually any other important aspect of the RCT. This tutorial explains the importance of these criteria and how to assess them. This tutorial also describes how many BIS FOES criteria can be initially assessed from the RCT Abstract while also directing readers to specific locations in the RCT article where additional important information can be found. We hope that the BIS FOES system will help healthcare trainees, but also potentially clinicians, researchers, and the general public, rapidly and thoroughly assess RCTs.

Suicide death over the first year of lithium versus valproate treatment in cohorts with and without bipolar disorder.

This study examined if lithium's association with suicide risk varies by diagnosis. We performed separate 1:1 high-dimensional propensity score (hdPS)-matching in US Veterans with and without bipolar disorder starting lithium or valproate. Among individuals with bipolar disorder, actively receiving lithium (compared to valproate) was not associated with suicide risk. However, in intent-to-treat analyses (following all individuals with bipolar disorder starting lithium or valproate for all 365 days, regardless of whether they stopped the medication), starting lithium was significantly associated with higher one-year risks of suicide (HR = 1.50, 95% CI: 1.05-2.15, p = 0.03). These intent-to-treat risks were attributable entirely to transiently elevated suicide risks observed among individuals no longer receiving lithium (significant at 180 days [HR = 6.10, CI: 1.37-27.3, p = 0.02] but not 365 days [HR = 2.05, CI: 0.88-4.79, p = 0.10]). Among individuals without bipolar disorder, depending on the analysis, actively receiving lithium was associated with nonsignificantly (HR = 0.43, CI: 0.15-1.20, p = 0.11) or significantly (HR = 0.28, CI: 0.08-0.98, p = 0.047) decreased one-year suicide risks. Study limitations included limited power, brief follow-up, and potential residual confounding. Residual confounding is suggested by the observation that more individuals diagnosed with suicidal ideation started lithium than valproate (with this difference being statistically significant for individuals with bipolar disorder, p = 0.0012). If it were possible to correct for this potential confounding, then the suicide-related risks associated with among individuals discontinuing lithium would be expected to be less, and the suicide-related benefits associated with actively receiving lithium (already statistically significant in some analyses among individuals without bipolar disorder) would be expected to increase. Further research is needed.

Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

Influence of Organizational Climate and Clinician Morale on Seclusion and Physical Restraint Use in Inpatient Psychiatric Units.

OBJECTIVES: Reducing seclusion and restraint use is a prominent focus of efforts to improve patient safety in inpatient psychiatry. This study examined the poorly understood relationship between seclusion and restraint rates and organizational climate and clinician morale in inpatient psychiatric units. METHODS: Facility-level data on hours of seclusion and physical restraint use in 111 U.S. Department of Veterans Affairs (VA) hospitals in 2014 to 2016 were obtained from the Centers for Medicare & Medicaid Services. Responses to an annual census survey were identified for 6646 VA inpatient psychiatry clinicians for the same period. We examined bivariate correlations and used a Poisson model to regress hours of seclusion and restraint use on morale and climate measures and calculated incident rate ratios (IRRs). RESULTS: The average physical restraint hours per 1000 patient hours was 0.33 (SD, 1.27; median, 0.05). The average seclusion hours was 0.31 (SD, 0.84; median, 0.00). Physical restraint use was positively associated with burnout (IRR, 1.76; P = 0.04) and negatively associated with engagement (IRR, 0.22; P = 0.01), psychological safety (IRR, 0.48; P < 0.01), and relational climate (IRR, 0.69; P = 0.04). Seclusion was positively associated with relational climate (IRR, 1.69; P = 0.03) and psychological safety (IRR, 2.12; P = 0.03). Seclusion use was also nonsignificantly associated with lower burnout and higher engagement. CONCLUSIONS: We found significant associations between organizational climate, clinician morale, and use of physical restraints and seclusion in VA inpatient psychiatric units. Health care organization leadership may want to consider implementing a broader range of initiatives that focus on improving organizational climate and clinician morale as one way to improve patient safety.

Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia.

OBJECTIVES: To determine whether elderly veterans with posttraumatic stress disorder (PTSD) and dementia are more likely to be prescribed second-generation antipsychotics (SGAs) than those with PTSD alone. DESIGN: National serial cross-sectional study. SETTING: Veterans Health Affairs inpatient and outpatient settings. PARTICIPANTS: Veterans aged 65 and older with PTSD (excluding schizophrenia or bipolar disorder) with or without concomitant dementia who received care from the Veterans Health Administration between 2003 and 2010 were identified using International Classification of Diseases, Ninth Revision, codes (N = 93,068; 11.1% with dementia). MEASUREMENTS: Trends in SGA prescribing and odds of being prescribed an SGA were determined using a multivariable logistic regression model adjusted for clinical, sociodemographic, and geographic covariates. RESULTS: Between 2004 and 2009, SGA prescribing declined annually from 7.0% to 5.1% of elderly veterans with PTSD without dementia and 13.2% to 8.9% in those with dementia; findings over time consistently indicated that veterans with PTSD and dementia had at least twice the odds of being prescribed an SGA as those without PTSD (odds ratios 2.03 (95% confidence interval (CI) = 1.82-2.26) to 2.33 (95% CI = 2.10-2.58). CONCLUSION: Although the prescribing of SGAs to elderly veterans with PTSD has decreased, prescribing an SGA to those with dementia remained consistently higher than for those with PTSD alone and is problematic given the high prevalence of medical comorbidities in this aging population coupled with the lack of compelling evidence for effectiveness of SGAs in individuals with dementia.

Associations Between Medication Class and Subsequent Augmentation of Depression Treatment in Privately Insured US Adults.

IMPORTANCE: Treatment augmentation is an important clinical decision in the pharmacotherapy for depression, yet few studies have examined the rates of treatment augmentation by medication class. OBJECTIVE: The aim of this study was to examine which initial pharmacotherapies for depression are more likely than others to result in subsequent treatment augmentation. METHODS: This study is a retrospective cohort analysis of administrative data of 214,705 privately insured US adults between the age of 18 and 64 years who were diagnosed with a new episode of depression in 2009. Propensity score-adjusted logistic regression and Cox regression were used to model the effect of the class of initial monotherapy on treatment augmentation. Risk adjustors included depression severity, comorbidities, provider type, insurance, and demographic characteristics. EXPOSURE: The class of initial monotherapy and the health care provider type were the main independent variables of interest. MAIN OUTCOME: The outcome was the augmentation of monotherapy. RESULTS: Thirty-four percent of individuals received treatment augmentation. Compared with selective serotonin reuptake inhibitor monotherapy, second-generation antipsychotics as the initial treatment were associated with significant increase in the likelihood of augmentation compared with the other classes (hazards ratio, 2.59; 95% confidence interval [CI], 2.51-2.68). This result was corroborated after propensity score adjustment (odds ratio, 2.85; 95% CI, 2.70-3.00) when comparing second-generation antipsychotics to the other classes of pharmacotherapy. The other significant predictor of treatment augmentation was the provider type. Mental health specialists were 27% more likely to augment a treatment compared with generalists (hazards ratio, 1.27; 95% CI, 1.25-1.30). CONCLUSIONS: The type of initial antidepressant therapy is associated with the chances of treatment augmentation. Second-generation antipsychotics progressed to augmentation more rapidly than the other classes.

Antidepressant Medication Treatment and Risk of Death.

OBJECTIVE: Although previous studies have assessed whether depression is a mortality risk factor, few have examined whether antidepressant medications (ADMs) influence mortality risk. METHODS: We estimated hazards of 1-year all-cause mortality associated with ADMs, with use occurring within 90 days of depression diagnosis among 720 821 patients who received treatment in a Veterans Health Administration facility during fiscal year 2006. We addressed treatment selection biases using conventional Cox regression, propensity-stratified Cox regression (propensity score), and 2 forms of marginal structural models. Models accounted for multiple potential clinical and demographic confounders, and sensitivity analyses compared findings by antidepressant class. RESULTS: Antidepressant medication use compared with no use was associated with significantly lower hazards of 1-year mortality risk in Cox (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.90-0.97) and propensity score estimates (HR, 0.94; 95% CI, 0.91-0.98), whereas marginal structural model-based estimates showed no difference in mortality risk when the exposure was specified as "as-treated" in every 90-day intervals of the 1-year follow-up (HR, 0.91; 95% CI, 0.66-1.26) but showed increased risk when specified as "intent-to-treat" (HR, 1.07; 95% CI, 1.02-1.13). CONCLUSIONS: Among patients treated with ADMs belonging to a single class in the first 90 days, there were no significant differences in 1-year all-cause mortality risks. When accounting for clinical and demographic characteristics and treatment selection bias, ADM use was associated with no excess harm.

Organizational Characteristics of Veterans Affairs Clinics With High and Low Utilization of Clozapine.

OBJECTIVE: Twenty to thirty percent of patients with schizophrenia experience treatment resistance. Clozapine is the only medication proven effective for treatment-resistant schizophrenia. However, in most settings less than 25% of patients with treatment-resistant schizophrenia receive clozapine. This study was conducted to identify facilitators of and barriers to clozapine use to inform development of interventions to maximize appropriate clozapine utilization. METHODS: Seventy semistructured phone interviews were conducted with key informants of clozapine processes at U.S. Department of Veterans Affairs medical centers in various U.S. regions, including urban and rural areas, with high (N=5) and low (N=5) rates of clozapine utilization. Interviewees included members of mental health leadership, psychiatrists, clinical pharmacists, and advanced practice nurses. Interviews were analyzed by using an emergent thematic strategy to identify barriers and facilitators related to clozapine prescribing. RESULTS: High utilization was associated with integration of nonphysician psychiatric providers and clear organizational processes and infrastructure for treatment of severe mental illness, for example, use of clozapine clinics and mental health intensive case management. Low utilization was associated with a lack of champions to support clozapine processes and with limited-capacity care systems. Obstacles identified at both high- and low-utilization sites included complex, time-consuming paperwork; reliance on a few individuals to facilitate processes; and issues related to transportation for patients living far from care facilities. CONCLUSIONS: Implementation efforts to organize, streamline, and simplify clozapine processes; development of a multidisciplinary clozapine clinic; increased capacity of existing clinics; and provision of transportation are reasonable targets to increase clozapine utilization.

The Business Case for Expanded Clozapine Utilization.

OBJECTIVE: In most settings, less than 25% of patients with treatment-resistant schizophrenia receive clozapine, the only medication proven effective for treatment-resistant schizophrenia. Therefore, a business case analysis was conducted to assess whether increasing clozapine utilization for treatment-resistant schizophrenia in a health care system would result in direct health care cost savings. METHODS: Veterans with treatment-resistant schizophrenia who were treated in the Veterans Health Administration (VHA) were studied. Treatment response, suicides, adverse drug reactions (and associated mortality), and effects on inpatient hospitalization related to clozapine were derived from a systematic review of published studies. A one-factor sensitivity analysis and a probabilistic sensitivity analysis (PSA) with Monte Carlo simulation were conducted to calculate the cost-benefits of increased clozapine utilization. RESULTS: Despite monitoring costs, in the base case analysis, the VHA would save $22,444 per veteran with treatment-resistant schizophrenia over the first year of clozapine therapy, primarily from 18.6 fewer inpatient days per patient. If current utilization was doubled, and 50% of those veterans continued clozapine treatment for one year, VHA would save an estimated $80 million. Cost savings were most sensitive to the proportion of treatment-resistant patients who received clozapine, decrease in inpatient days, cost of inpatient stays, clozapine response rate, and number of patients with treatment-resistant schizophrenia. In the PSA, initiation of clozapine for all VHA patients with treatment-resistant schizophrenia who were not currently treated with clozapine would save at least $290 million in 95% of simulations. CONCLUSIONS: Increased clozapine utilization would result in net cost savings for the VHA.

Development and Validation of a Computerized-Adaptive Test for PTSD (P-CAT).

OBJECTIVE: The primary purpose was to develop, field test, and validate a computerized-adaptive test (CAT) for posttraumatic stress disorder (PTSD) to enhance PTSD assessment and decrease the burden of symptom monitoring. METHODS: Data sources included self-report and interviewer-administered diagnostic interviews. The sample included 1,288 veterans. In phase 1, 89 items from a previously developed PTSD item pool were administered to a national sample of 1,085 veterans. A multidimensional graded-response item response theory model was used to calibrate items for incorporation into a CAT for PTSD (P-CAT). In phase 2, in a separate sample of 203 veterans, the P-CAT was validated against three other self-report measures (PTSD Checklist, Civilian Version; Mississippi Scale for Combat-Related PTSD; and Primary Care PTSD Screen) and the PTSD module of the Structured Clinical Interview for DSM-IV. RESULTS: A bifactor model with one general PTSD factor and four subfactors consistent with DSM-5 (reexperiencing, avoidance, negative mood-cognitions, and arousal), yielded good fit. The P-CAT discriminated veterans with PTSD from those with other mental health conditions and those with no mental health conditions (Cohen's d effect sizes >.90). The P-CAT also discriminated those with and without a PTSD diagnosis and those who screened positive versus negative for PTSD. Concurrent validity was supported by high correlations (r=.85-.89) with the validation measures. CONCLUSIONS: The P-CAT appears to be a promising tool for efficient and accurate assessment of PTSD symptomatology. Further testing is needed to evaluate its responsiveness to change. With increasing availability of computers and other technologies, CAT may be a viable and efficient assessment method.

The Ascendancy of Second-Generation Antipsychotics as Frontline Antimanic Agents.

INTRODUCTION: Knowledge of the factors affecting the adoption of new medications can enhance mental health care and guide quality improvement and policy development. Food and Drug Administration indications for treating bipolar disorder with several second-generation antipsychotics (SGAs) in the 2000s represent an opportunity to identify factors that impact the spread of a then-innovative treatment through a new population. METHODS: Analysis of Department of Veterans Affairs administrative data identified the population of 170,811 veterans diagnosed with bipolar disorder from 2003 to 2010. We analyzed time trends and predictors of antimanic choice (SGA vs other) among the 40,512 outpatients with bipolar disorder who initiated their first VA outpatient antimanic prescription, using multinomial logistic regression in month-by-month analyses. We conducted classwise analyses and investigated prespecified predictors among specific agents. RESULTS: In classwise analyses, SGAs supplanted lithium, valproate, and carbamazepine/oxcarbazepine as the most commonly initiated antimanics by 2007. Psychosis, but not other indices of severity, predicted SGA initiation. Demographic analyses did not identify substantial disparities in initiation of SGAs. Drug-specific analyses revealed some consideration of medical comorbidities in choosing among specific antimanic agents, although effect sizes were small. Most patients initiating an antimanic had received an antidepressant in the previous year. DISCUSSION: Second-generation antipsychotics quickly became the frontline antimanic treatment for bipolar disorder, although antidepressants most commonly predated antimanic prescriptions. Second-generation antipsychotics were used for a broad range of patients rather than being restricted to a severely ill subpopulation. The modest association of antimanic choice with relevant medical comorbidities suggests that continued attention to quality prescribing practices is warranted.