Dara Ganoczy

Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study

Objective To study the association between benzodiazepine prescribing patterns including dose, type, and dosing schedule and the risk of death from drug overdose among US veterans receiving opioid analgesics. Design Case-cohort study. Setting Veterans Health Administration (VHA), 2004-09. Participants US veterans, primarily male, who received opioid analgesics in 2004-09. All veterans who died from a drug overdose (n=2400) while receiving opioid analgesics and a random sample of veterans (n=420 386) who received VHA medical services and opioid analgesics. Main outcome measure Death from drug overdose, defined as any intentional, unintentional, or indeterminate death from poisoning caused by any drug, determined by information on cause of death from the National Death Index. Results During the study period 27% (n=112 069) of veterans who received opioid analgesics also received benzodiazepines. About half of the deaths from drug overdose (n=1185) occurred when veterans were concurrently prescribed benzodiazepines and opioids. Risk of death from drug overdose increased with history of benzodiazepine prescription: adjusted hazard ratios were 2.33 (95% confidence interval 2.05 to 2.64) for former prescriptions versus no prescription and 3.86 (3.49 to 4.26) for current prescriptions versus no prescription. Risk of death from drug overdose increased as daily benzodiazepine dose increased. Compared with clonazepam, temazepam was associated with a decreased risk of death from drug overdose (0.63, 0.48 to 0.82). Benzodiazepine dosing schedule was not associated with risk of death from drug overdose. Conclusions Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose in a dose-response fashion.

Trends in Antipsychotic Use in Dementia 1999-2007

CONTEXT Use of atypical antipsychotics for neuropsychiatric symptoms of dementia increased markedly in the 1990s. Concerns about their use began to emerge in 2002, and in 2005, the US Food and Drug Administration warned that use of atypical antipsychotics in dementia was associated with increased mortality. OBJECTIVE To examine changes in atypical and conventional antipsychotic use in outpatients with dementia from 1999 through 2007. DESIGN Time-series analyses estimated the effect of the various warnings on atypical and conventional antipsychotic usage using national Veterans Affairs data across 3 periods: no warning (1999-2003), early warning (2003-2005), and black box warning (2005-2007). SUBJECTS Patients aged 65 years or older with dementia (n = 254 564). MAIN OUTCOME MEASURES Outpatient antipsychotic use (percentage of patients, percentage of quarterly change, and difference between consecutive study periods). RESULTS In 1999, 17.7% (95% confidence interval [CI], 17.2-18.1) of patients with dementia were using atypical or conventional antipsychotics. Overall use began to decline during the no-warning period (rate per quarter, -0.12%; 95% CI, -0.16 to -0.07; P < .001). Following the black box warning, the decline continued (rate, -0.26%; 95% CI, -0.34 to -0.18; P < .001), with a significant difference between the early and black box warning periods (P = .006). Use of atypical antipsychotics as a group increased during the no-warning period (rate, 0.23; 95% CI, 0.17-0.30; P < .001), started to decline during the early-warning period (rate, -0.012; 95% CI, -0.14 to 0.11; P = .85), and more sharply declined during the black box warning period (rate, -0.27; 95% CI, -0.36 to -0.18; P < .001). Olanzapine and risperidone showed declining rates and quetiapine showed an increase during the early-warning period, but rates of use for all 3 antipsychotics declined during the black box warning period. In the black box warning period, there was a small but significant increase in anticonvulsant prescriptions (rate, 0.117; 95% CI, 0.08-0.16; P < .001). CONCLUSIONS Use of atypical antipsychotics began to decline significantly in 2003, and the Food and Drug Administration advisory was temporally associated with a significant acceleration in the decline.

Comorbid anxiety as a suicide risk factor among depressed veterans

Background: Depressive disorders greatly increase suicide risk; however, little is known about the contribution of comorbid anxiety disorders or anxiety symptoms to the risk of suicide death among depressed patients. We examined whether depressed veterans with comorbid anxiety had higher risks of suicide death. Methods: Using VA administrative databases we identified 887,859 patients with depression. We then used univariate and multivariate logistic regression, controlling for demographics and substance use disorders, to determine the odds ratios of completed suicide associated with individual comorbid anxiety disorders, the presence of any comorbid anxiety disorder, the prescription of an antianxiety medication, or the prescription of a high dose of an antianxiety medication. Results: In multivariate analyses, the odds of completed suicide were significantly increased for patients with panic disorder (OR 1.26, 95% CI: 1.04–1.53), generalized anxiety disorder (OR 1.27, 95% CI: 1.09–1.47), and anxiety disorder, not otherwise specified (OR 1.25, 95% CI: 1.12–1.38). The odds of completed suicide were also greater among patients who received any antianxiety medication (OR 1.71, 95% CI: 1.55–1.88), and were further increased among those who received high dose treatment (OR 2.26, 95% CI: 1.98–2.57). Odds of completed suicide were decreased among patients with comorbid posttraumatic stress disorder (OR 0.87, 95% CI: 0.77–0.97), and there was no statistically significant relationship between social phobia, obsessive–compulsive disorder, and all other anxiety disorders and suicide. Conclusions: These findings emphasize the importance of comorbid anxiety disorders and symptoms in increasing suicide risk among depressed patients and may inform suicide prevention efforts among these patients. Depression and Anxiety, 2009.

Using A Pharmacy-Based Intervention To Improve Antipsychotic Adherence Among Patients With Serious Mental Illness

Background: Similar to patients with other chronic disorders, patients with serious mental illness (SMI) are often poorly adherent with prescribed medications. Objective: We conducted a randomized controlled trial examining the effectiveness of a pharmacy-based intervention (Meds-Help) in increasing antipsychotic medication adherence among Department of Veterans Affairs (VA) patients with SMI. We also examined the impact of Meds-Help on psychiatric symptoms, quality of life, and satisfaction with care. Methods: We enrolled 118 patients from 4 VA facilities with schizophrenia, schizoaffective, or bipolar disorder who were on long-term antipsychotics but had antipsychotic medication possession ratios (MPRs) <0.8 in the prior year. Patients were randomized to usual care (UC; n = 60) or the pharmacy-based intervention (Meds-Help; n = 58). We reassessed adherence at 6 and 12 months, at which time patients completed Positive and Negative Symptom Scales (PANSS), Quality of Well-being Scales (QWB), and Client Satisfaction Questionnaires (CSQ-8). Results: Prior to enrollment, Meds-Help and UC patients had mean antipsychotic MPRs of 0.54 and 0.55, respectively. At 6 months, mean MPRs were 0.91 for Meds-Help and 0.64 for UC patients; at 12 months, they were 0.86 for Meds-Help and 0.62 for UC patients. In multivariate analyses adjusting for patient factors, Meds-Help patients had significantly higher MPRs at 6 and 12 months (P < .0001). There were no significant differences between groups in PANSS, QWB, or CSQ-8 scores, but power to detect small effects was limited. Conclusions: Congruent with prior studies of patients with other disorders, a practical pharmacy-based intervention increased antipsychotic adherence among patients with SMI. However, SMI patients may require additional care management components to improve outcomes.

Evaluation of the FDA Warning Against Prescribing Citalopram at Doses Exceeding 40 mg

OBJECTIVE A recent Food and Drug Administration (FDA) warning cautioned that citalopram dosages exceeding 40 mg/day may cause abnormal heart rhythms, including torsade de pointes. The authors assessed relationships between citalopram use and ventricular arrhythmias and mortality. METHOD A cohort study was conducted using Veterans Health Administration data between 2004 and 2009 from depressed patients who received a prescription for citalopram (N=618,450) or for sertraline (N=365,898), a comparison medication with no FDA warning. Cox regression models, adjusted for demographic and clinical characteristics, were used to examine associations of antidepressant dosing with ventricular arrhythmia and cardiac, noncardiac, and all-cause mortality. RESULTS Citalopram daily doses >40 mg were associated with lower risks of ventricular arrhythmia (adjusted hazard ratio=0.68, 95% CI=0.61-0.76), all-cause mortality (adjusted hazard ratio=0.94, 95% CI=0.90-0.99), and noncardiac mortality (adjusted hazard ratio=0.90, 95% CI=0.86-0.96) compared with daily doses of 1-20 mg. No increased risks of cardiac mortality were found. Citalopram daily doses of 21-40 mg were associated with lower risks of ventricular arrhythmia (adjusted hazard ratio=0.80, 95% CI=0.74-0.86) compared with dosages of 1-20 mg/day but did not have significantly different risks of any cause of mortality. The sertraline cohort revealed similar findings, except there were no significant associations between daily dose and either all-cause or noncardiac mortality. CONCLUSIONS This large study found no elevated risks of ventricular arrhythmia or all-cause, cardiac, or noncardiac mortality associated with citalopram dosages >40 mg/day. Higher dosages were associated with fewer adverse outcomes, and similar findings were observed for a comparison medication, sertraline, not subject to the FDA warning. These results raise questions regarding the continued merit of the FDA warning.

Trends and regional variation in opioid overdose mortality among Veterans Health Administration patients, fiscal year 2001 to 2009.

Objectives:Opioid-related mortality has increased in the United States in the past decade. The purpose of this study was to examine trends and regional variation in opioid prescribing and overdose rates in a national health system, the Veterans Health Administration. Materials and Methods:Annual cohorts of Veterans Health Administration patients were identified on the basis of medical records, and overdose mortality was determined from National Death Index records. State-level prescribing and overdose rates were mapped to provide information on regional variability. Results:There were significant increases between 2001 and 2009 in the rate of overdoses associated with nonsynthetic opioids (&bgr;=0.53, 95% confidence interval, 0.35, 0.70) and methadone (&bgr;=0.63, 95% confidence interval, 0.37, 0.90) but not synthetic/semisynthetic opioids. State-level overdose rates had a moderate correlation with the average proportion of patients in that state receiving opioids (r=0.29). Discussion:The present study demonstrates that the increases in prescription opioid overdoses observed in the general population are also found in the patient population of a national health system and provides further evidence of the population-level association between trends in opioid prescribing and opioid overdose deaths. There is substantial regional variation in both opioid prescribing and opioid-related overdose rates, and these data can inform region-specific overdose prevention strategies and opioid policy.

Hazardous Drinking and Family Functioning in National Guard Veterans and Spouses Postdeployment

The current study examined rates of alcohol misuse among National Guard (NG) service members and their spouses/partners, concordance of drinking behaviors among couples, and the effects of alcohol misuse, depression, and posttraumatic stress disorder (PTSD) on three measures of family functioning. This study is important because it addresses the topics of heavy drinking and family functioning in an at-risk population-NG service members returning from a combat zone deployment. We surveyed NG service members (1,143) and their partners (674) 45-90 days after returning from a military deployment. Service member rates of hazardous drinking were 29.2% and spouses/partners 10.7%. Of the 661 linked couples, 26.2% were discrepant where only one member met the criteria for hazardous drinking and 5.4% were congruent for alcohol misuse where both members met hazardous drinking criteria. Service members belonging to either congruent or discrepant drinking groups were more distressed in their marriages/relationships than those in the nonhazardous group. In dyadic analyses, an unexpected partner effect was found for parenting outcomes; that is, when service members drink more, their spouses/partners are less stressed when it comes to parenting. Importantly, both service member and spouse/partner depression was significantly associated with negative family outcomes. Results from this study suggest that when working with these families, it is important to understand the drinking status of both soldier and spouse and to treat depression in addition to alcohol misuse.

Predictors of Suicide in Patient Charts Among Patients With Depression in the Veterans Health Administration Health System: Importance of Prescription Drug and Alcohol Abuse

OBJECTIVE To identify factors recorded in electronic medical chart progress notes associated with suicide among patients who had received treatment for depression. METHOD The retrospective study sample consisted of 324 randomly selected US Veterans Health Administration (VHA) patients treated for depression who died by suicide from April 1, 1999, to September 30, 2004, stratified by geographic region, gender, and year of depression cohort entry and 312 control patients with depression who were alive on the date of suicide death (index date) and were from the same stratum as the matched suicide patient. In addition to constructing variables from administrative data, variables were abstracted from electronic medical chart notes in the year prior to the index date in 5 categories: clinical symptoms and diagnoses, substance use, life stressors, behavioral/ideation measures (eg, suicide attempts), and treatments received. Logistic regression was used to assess the associations. RESULTS Even after we adjusted for administratively available data, suicidal behaviors and substance-related variables were the strongest independent predictors of suicide. Prescription drug misuse had an odds ratio (OR) of 6.8 (95% CI, 2.5-18.5); history of suicide attempts, 6.6 (95% CI, 1.7-26.4); and alcohol abuse/dependence, 3.3 (95% CI, 1.9-5.7). Difficulty with access to health care was a predictor of suicide (OR = 2.9; 95% CI, 1.3-6.3). Receipt of VHA substance abuse treatment was protective (OR = 0.4; 95% CI, 0.1-0.9). CONCLUSIONS Prescription drug and alcohol misuse assessments should be prioritized in suicide assessments among depressed patients. Additionally, behavioral measures noted in electronic chart records may be useful in health system monitoring and surveillance and can potentially be accessed using word search or natural language processing approaches.

Suicide risk assessment received prior to suicide death by Veterans health administration patients with a history of depression

OBJECTIVE To examine the quality of suicide risk assessment provided to veterans with a history of depression who died by suicide between 1999 and 2004. METHOD We conducted a case-control study of suicide risk assessment information recorded in 488 medical charts of veterans previously diagnosed with major depression, depression not otherwise specified, dysthymia, or other, less common ICD-9-CM depression codes. Patients dying by suicide from April 1999 through September 2004 or comparison patients (n = 244 pairs) were matched for age, sex, entry year, and region. RESULTS Seventy-four percent of patients with a history of depression received a documented assessment of suicidal ideation within the past year, and 59% received more than 1 assessment. However, 70% of those who died of suicide did not have a documented assessment for suicidal ideation at their final Veterans Health Administration (VHA) visit, even if that visit occurred within 0 through 7 days prior to suicide death. Most patients dying by suicide denied suicidal ideation when assessed (85%; 95% CI, 75%-92%), even just 0 through 7 days prior to suicide death (73%; 95% CI, 39%-94%). Suicidal ideation was assessed more frequently during outpatient final visits with mental health providers (60%) than during outpatient final visits with primary care (13%) or other non-mental health providers (10%, P < .0001). CONCLUSIONS Most VHA patients with a history of depression received some suicide risk assessment within the past year, but suicide risk assessments were infrequently administered at the final visit of patients who eventually died by suicide. Among patients who had assessments, denial of suicidal ideation appeared to be of limited value. Practice changes are needed to improve suicide risk assessment among patients with histories of depression, including the development of assessment and prevention strategies that are less dependent on the presence or disclosure of suicidal ideation at scheduled medical visits.

Predictors of suicidal ideation among depressed veterans and the interpersonal theory of suicide

BACKGROUND We assessed whether key constructs of the interpersonal theory of suicide were associated with suicidal ideation in depressed US Veterans. METHODS 443 patients of the Veterans Health Administration diagnosed with a depressive disorder completed the Beck Depression Inventory, Interpersonal Support Evaluation List, and Beck Hopelessness Scale, from which we derived measures of burdensomeness, belongingness, and hopelessness consistent with the interpersonal theory of suicide. Measures of active and passive suicidal ideation were constructed from the Beck Suicide Scale and Beck Depression Inventory obtained at baseline and 3-months follow-up. Multivariable logistic regression was used to identify predictors of passive and active suicidal ideation while adjusting for demographic characteristics and somatic-affective symptoms of depression (e.g., anhedonia, insomnia). RESULTS Burdensomeness and hopelessness were significantly associated with passive suicidal ideation at baseline and 3 months follow-up, but belongingness and the interaction between belongingness and burdensomeness were not significant predictors as proposed by the interpersonal theory of suicide. Somatic-affective depressive symptoms, but not any of the main effects predicted by the interpersonal theory of suicide or their interactions, were associated with active suicidal ideation at baseline. No factors were consistently associated with active suicidal ideation at 3 months follow-up. LIMITATIONS The measure of burdensomeness used in this study only partially represents the construct described by the interpersonal theory of suicide. CONCLUSION We found little support for the predictions of the interpersonal theory of suicide. Hopelessness appears to be an important determinant of passive suicidal ideation, while somatic-affective depression symptoms may be a key contributor to active suicidal ideation.