Assessing Responsiveness of Health Systems to Drug Safety Warnings.

OBJECTIVE: In 2011-2012 the U.S. Food and Drug Administration (FDA) issued safety announcements cautioning providers against prescribing high doses of citalopram given concerns for QT prolongation. The authors evaluated Veterans Affairs (VA) national trends in citalopram use and dose compared with alternative antidepressants after the FDA warnings. METHODS: Time series analyses estimated the effect of the FDA warnings on citalopram and other antidepressant across three periods: before the first FDA warning in August 2011, after the 2011 FDA warning until the second warning in March 2012, and after the 2012 FDA warning. In a National VA health system, adult VA outpatients prescribed citalopram or alternative antidepressants from February 2010 to September 2013 were studied. Outpatient use of high-dose citalopram (>40 or >20 mg daily in adults aged > 60 years) including the proportion of patients prescribed citalopram and difference between study periods. RESULTS: Between the first and second FDA warnings, among patients aged 18-60, high-dose citalopram use decreased by 2.0% per month (p < 0.001) and by 1.9% per month (p < 0.001) for older adults. After the second FDA warning in 2012, 30.7% of older patients remained on doses higher than the newly recommended dose of 20 mg. Reductions in overall use of citalopram were accompanied by significant increases in prescriptions of alternative antidepressants, with sertraline most widely prescribed. CONCLUSION: Although trends in high-dose citalopram use declined after the 2011-2012 FDA warnings, roughly one-third of older adults still remained on higher than recommended doses. Concomitant increases in sertraline and other antidepressant prescriptions suggest potential substitution of these medications for citalopram.

Unintended Consequences of Adjusting Citalopram Prescriptions Following the 2011 FDA Warning.

OBJECTIVES: In 2011, the U.S. Food and Drug Administration (FDA) issued a safety announcement cautioning providers against prescribing citalopram above 40 mg per day given concerns for QT prolongation. We assessed the impact of a health system quality improvement initiative to identify patients taking higher than the recommended dose of citalopram. DESIGN: Retrospective cohort study. SETTING: Nine primary care clinics within the University of Michigan from March 2012 to February 2013. PARTICIPANTS: Adult patients taking a higher-than-recommended dose of citalopram following the FDA warning in 2011 (N = 199). MEASUREMENTS: Frequency of EKG monitoring, clinical factors associated with patients whose citalopram dose or use was adjusted, and potential impact of these changes on overall health care utilization was assessed. RESULTS: In patients prescribed higher-than-recommended doses of citalopram and who received a note from a pharmacist regarding the FDA warnings, only 8.5% received electrocardiogram (EKG) monitoring. Patients who were converted to an alternative antidepressant from citalopram were more likely to receive subsequent new prescriptions for benzodiazepines and sedative hypnotics (χ2 = 7.9, p = 0.048). Patients who had any adjustments to their antidepressant medication had greater overall health care utilization (OR: 25.0; 95% CI: 5.7-109.6; p < 0.001) than patients remaining on the same dose of citalopram. CONCLUSIONS: Despite a targeted quality intervention to address the FDA warning regarding citalopram, the warning was associated with low levels of EKG monitoring, increased anxiolytic and sedative medication use, and higher healthcare utilization. This finding may represent destabilization of patients on previously therapeutic doses of their antidepressant and an unintended consequence of the FDA warning.

Management of older adults with dementia who present to emergency services with neuropsychiatric symptoms.

OBJECTIVE: Our aim is to evaluate if and how neuropsychiatric symptoms (NPS) of dementia influence the management and disposition of older adults who present to emergency care settings. METHODS: This is a retrospective cohort study that involved the medical and psychiatric emergency departments of a tertiary academic medical center. Participants included patients ≥65 years of age with dementia who presented between 1 February 2012 and 16 July 2014 (n = 347). Subjects with documented NPS (n = 78) were compared with a group of subjects without documented NPS (n = 78) randomly selected from the overall group with dementia. The groups with and without NPS were compared on demographic, clinical, management, and disposition characteristics. RESULTS: Patients with NPS were more likely to have additional diagnostic testing performed and receive psychotropic medications including benzodiazepines and antipsychotics. Significantly fewer patients with NPS (59.0%) returned to their original setting from the emergency department than patients without NPS (76.9%). Among patients with NPS, those who had a motor disturbance were more likely to receive psychotropic medications than patients who did not have a motor disturbance. Depression/dysphoria, anxiety, disinhibition, irritability/lability, and motor disturbance were all associated with transfer from medical to psychiatric emergency department. Patients with depression/dysphoria or anxiety were more likely to be psychiatrically hospitalized. CONCLUSIONS: There are significant differences in the management of dementia with and without NPS in the emergency room setting. Developing and implementing successful methods to manage NPS in the emergency department and outpatient setting could potentially lead to less emergent psychotropic administration and reduce hospitalizations. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Responsiveness of Veterans Affairs Health Care System to Zolpidem Safety Warnings.

STUDY OBJECTIVES: Sedative hypnotic medications are routinely prescribed for insomnia treatment, but have been associated with significant risks of morning-after impairment. We evaluated responsiveness in the Veterans Health Administration (VHA) facilities to two drug safety warnings recommending against high-dose zolpidem use-a 2007 Veterans Administration Pharmacy Benefits Management Service warning and a 2013 Food and Drug Administration (FDA) warning. METHODS: We used interrupted time-series design to assess how the two warnings influenced prescribing within the VHA in outpatients from 2005 to 2014. We assessed two outcomes: monthly outpatient use of (1) higher-than-recommended dose of zolpidem among zolpidem users and (2) any-dose zolpidem among all VHA users. In sensitivity analyses, we compared zolpidem prescribing to prescribing other sleep medications not subject to safety warnings. RESULTS: After the 2007 VHA warning, high-dose zolpidem use decreased significantly among both sexes from approximately 10% to 2%. Following the 2013 FDA warning, high-dose zolpidem use declined again; however, approximately half of women Veterans remained on high doses. Overall zolpidem use nearly quadrupled between the 2007 VHA and 2013 FDA warnings, but the overall use declined after the 2013 FDA warning. Increase in sedating antidepressant use was seen after the FDA warning, suggesting potential substitution. CONCLUSIONS: Higher than recommended dose use within the VHA decreased after each zolpidem high dose warning. Although overall use also decreased after the FDA warning, almost 50% of high-dose use among women Veterans is concerning. Different strategies to communicate the warnings should be examined. COMMENTARY: A commentary on this article appears in this issue on page 1093.

Effectively implementing FDA medication alerts utilizing patient centered medical home clinical pharmacists.

FDA medication alerts can be successfully implemented within patient centered medical home (PCMH) clinics utilizing clinical pharmacists. Targeted selection of high-risk patients from an electronic database allows PCMH pharmacists to prioritize assessments. Trusting relationships between PCMH clinical pharmacists and primary care providers facilitates high response rates to pharmacist recommendations. This health system approach led by PCMH pharmacists provides a framework for proactive responses to FDA safety alerts and medication related quality measure improvement.

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.