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.

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.

Mortality associated with lithium and valproate treatment of US Veterans Health Administration patients with mental disorders.

BackgroundThe mood stabilisers lithium and valproate might plausibly have differing associations with mortality because of differing effects on mental health and various physiological indicators.AimsTo assess associations between lithium, valproate and non-suicide mortality.MethodIntention-to-treat, propensity score-matched cohort study.ResultsLithium was associated with significantly reduced non-suicide mortality in the intent-to-treat cohort over 0-90 days (hazard ratio (HR) = 0.67, 95% CI 0.51-0.87) but not longer. In secondary analyses, a sizeable reduction in mortality was observed during active treatment with lithium across all time periods studied (for example 365-day HR = 0.62, 95% CI 0.45-0.84), but significantly increased risks were observed among patients discontinuing lithium by 180 days (HR = 1.54, 95% CI 1.01-2.37).ConclusionsPatients initiating lithium had lower non-suicide mortality over 0-90 days than patients initiating valproate and consistently lower non-suicide mortality among patients maintaining treatment, but elevated risk among patients discontinuing treatment by 180 days. Although residual confounding or selection effects cannot be excluded, this study suggests potential benefits to enhancing lithium treatment persistence and the monitoring of patients discontinuing lithium. There is a need for further research.

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.

Patterns of initiation of second generation antipsychotics for bipolar disorder: a month-by-month analysis of provider behavior.

BACKGROUND: Several second generation antipsychotics (SGAs) received FDA approval for bipolar disorder in the 2000s. Although efficacious, they have been costly and may cause significant side effects. Little is known about the factors associated with prescribers' decisions to initiate SGA prescriptions for this condition. METHODS: We gathered administrative data from the Department of Veterans Affairs on 170,713 patients with bipolar disorder between fiscal years 2003-2010. Patients without a prior history of taking SGAs were considered eligible for SGA initiation during the study (n =126,556). Generalized estimating equations identified demographic, clinical, and comorbidity variables associated with initiation of an SGA prescription on a month-by-month basis. RESULTS: While the number of patients with bipolar disorder using SGAs nearly doubled between 2003 and 2010, analyses controlling for patient characteristics and the rise in the bipolar population revealed a 1.2% annual decline in SGA initiation during this period. Most medical comorbidities were only modestly associated with overall SGA initiation, although significant differences emerged among individual SGAs. Several markers of patient severity predicted SGA initiation, including previous hospitalizations, psychotic features, and a history of other antimanic prescriptions; these severity markers became less firmly linked to SGA initiation over time. Providers in the South were somewhat more likely to initiate SGA treatment. CONCLUSIONS: The number of veterans with bipolar disorder prescribed SGAs is rising steadily, but this increase appears primarily driven by a corresponding increase in the bipolar population. Month-by-month analyses revealed that higher illness severity predicted SGA initiation, but that this association may be weakening over time.

Suicide risk in Veterans Health Administration patients with mental health diagnoses initiating lithium or valproate: a historical prospective cohort study.

BACKGROUND: Lithium has been reported in some, but not all, studies to be associated with reduced risks of suicide death or suicidal behavior. The objective of this nonrandomized cohort study was to examine whether lithium was associated with reduced risk of suicide death in comparison to the commonly-used alternative treatment, valproate. METHODS: A propensity score-matched cohort study was conducted of Veterans Health Administration patients (n=21,194/treatment) initiating lithium or valproate from 1999-2008. RESULTS: Matching produced lithium and valproate treatment groups that were highly similar in all 934 propensity score covariates, including indicators of recent suicidal behavior, but recent suicidal ideation was not able to be included. In the few individuals with recently diagnosed suicidal ideation, a significant imbalance existed with suicidal ideation more prevalent at baseline among individuals initiating lithium than valproate (odds ratio (OR) 1.30, 95% CI 1.09, 1.54; p=0.003). No significant differences in suicide death were observed over 0-365 days in A) the primary intent-to-treat analysis (lithium/valproate conditional odds ratio (cOR) 1.22, 95% CI 0.82, 1.81; p=0.32); B) during receipt of initial lithium or valproate treatment (cOR 0.86, 95% CI 0.46, 1.61; p=0.63); or C) after such treatment had been discontinued/modified (OR 1.51, 95% CI 0.91, 2.50; p=0.11). Significantly increased risks of suicide death were observed after the discontinuation/modification of lithium, compared to valproate, treatment over the first 180 days (OR 2.72, 95% CI 1.21, 6.11; p=0.015). CONCLUSIONS: In this somewhat distinct sample (a predominantly male Veteran sample with a broad range of psychiatric diagnoses), no significant differences in associations with suicide death were observed between lithium and valproate treatment over 365 days. The only significant difference was observed over 0-180 days: an increased risk of suicide death, among individuals discontinuing or modifying lithium, compared to valproate, treatment. This difference could reflect risks either related to lithium discontinuation or higher baseline risks among lithium recipients (i.e., confounding) that became more evident when treatment stopped. Our findings therefore support educating patients and providers about possible suicide-related risks of discontinuing lithium even shortly after treatment initiation, and the close monitoring of patients after lithium discontinuation, if feasible. If our findings include residual confounding biasing against lithium, however, as suggested by the differences observed in diagnosed suicidal ideation, then the degree of beneficial reduction in suicide death risk associated with active lithium treatment would be underestimated. Further research is urgently needed, given the lack of interventions against suicide and the uncertainties concerning the degree to which lithium may reduce suicide risk during active treatment, increase risk upon discontinuation, or both.

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.

Validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use.

BACKGROUND: Observational research frequently uses administrative codes for mental health or substance use diagnoses and for important behaviours such as suicide attempts. We sought to validate codes (International Classification of Diseases, 9th edition, clinical modification diagnostic and E-codes) entered in Veterans Health Administration administrative data for patients with depression versus a gold standard of electronic medical record text ("chart notation"). METHODS: Three random samples of patients were selected, each stratified by geographic region, gender, and year of cohort entry, from a VHA depression treatment cohort from April 1, 1999 to September 30, 2004. The first sample was selected from patients who died by suicide, the second from patients who remained alive on the date of death of suicide cases, and the third from patients with a new start of a commonly used antidepressant medication. Four variables were assessed using administrative codes in the year prior to the index date: suicide attempt, alcohol abuse/dependence, drug abuse/dependence and tobacco use. RESULTS: Specificity was high (≥ 90%) for all four administrative codes, regardless of the sample. Sensitivity was ≤75% and was particularly low for suicide attempt (≤ 17%). Positive predictive values for alcohol dependence/abuse and tobacco use were high, but barely better than flipping a coin for illicit drug abuse/dependence. Sensitivity differed across the three samples, but was highest in the suicide death sample. CONCLUSIONS: Administrative data-based diagnoses among VHA records have high specificity, but low sensitivity. The accuracy level varies by different diagnosis and by different patient subgroup.

Using the patient safety indicators to detect potential safety events among US veterans with psychotic disorders: clinical and research implications.

OBJECTIVE: Patients with psychotic disorders often experience poorer health outcomes, but whether they experience increased risks of medical errors/patient safety events is less clear. A single state-level US study found acute care inpatients with schizophrenia were at higher risk of incurring some of the Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs). We examined a nationwide sample of US Veteran's Health Administration (VHA) acute care inpatients to determine the rates observed among patients with psychotic disorders for a larger set of PSIs. DESIGN: Retrospective cohort analysis using administrative data. PARTICIPANTS: and SETTING: Veterans with (n = 50 328) and without (n = 1 812 897) psychotic disorders (schizophrenia/schizoaffective disorder and other psychoses) admitted for acute care to US VHA hospitals during fiscal years 2003-06. METHODS: and MAIN OUTCOME MEASURES: PSI rates were calculated using AHRQ's PSI software. RESULTS: Patients with psychotic disorders had significantly higher rates of postoperative respiratory failure, postoperative wound dehiscence and decubitus ulcer than those without psychotic disorders, although postoperative respiratory failures rates were not significantly higher among patients specifically diagnosed with schizophrenia. Patients with psychotic disorders had significantly lower rates of accidental puncture/laceration, foreign body left in during procedure and failure to rescue. However, the odds of failure to rescue were not significantly lower among surgical patients (the current focus of this PSI). CONCLUSIONS: Acute care inpatient veterans with psychotic disorders experienced higher rates of several PSIs, but lower rates of others. Whether lower rates of certain PSIs reflect better or worse care for this population is uncertain.

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.

Antidepressant adequacy and work status among medicaid enrollees with disabilities: a restriction-based, propensity score-adjusted analysis.

Abstract This cross-sectional study of adult survey respondents with disability and depression (n = 199) enrolled in Massachusetts' Medicaid program examined the association of adequately or inadequately prescribed antidepressant treatment and self-reported work status using conditional logistic regression, controlling for age, gender, race, marital status, education, receipt of SSI/SSDI, self-reported disabling condition, and health status. Confounding by severity was addressed by two methods: restriction of our sample and subsequent stratification by propensity score. Individuals receiving adequate antidepressant treatment had an increased odds of working compared to individuals receiving inadequate treatment, both in analyses in which restriction was used to limit confounding (OR = 3.45, 95% CI = 1.15-10.32, P < .03), and in analyses which combined restriction with adjustment by propensity score stratification (OR = 3.04, 95% CI = 1.01-9.62, P < .05). Among this sample of Medicaid enrollees with disability and depression, those receiving adequate antidepressant treatment were significantly more likely to report working.

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.