Lisa S. Seyfried

Antipsychotics, Other Psychotropics, and the Risk of Death in Patients With Dementia: Number Needed to Harm

IMPORTANCE Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear. OBJECTIVE To determine the absolute mortality risk increase and number needed to harm (NNH) (ie, number of patients who receive treatment that would be associated with 1 death) of antipsychotic, valproic acid and its derivatives, and antidepressant use in patients with dementia relative to either no treatment or antidepressant treatment. DESIGN, SETTING, AND PARTICIPANTS A retrospective case-control study was conducted in the Veterans Health Administration from October 1, 1998, through September 30, 2009. Participants included 90,786 patients 65 years or older with a diagnosis of dementia. Final analyses were conducted in August 2014. EXPOSURES A new prescription for an antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant (46,008 medication users). MAIN OUTCOMES AND MEASURES Absolute change in mortality risk and NNH over 180 days of follow-up in medication users compared with nonmedication users matched on several risk factors. Among patients in whom a treatment with medication was initiated, mortality risk associated with each agent was also compared using the antidepressant group as the reference, adjusting for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics. Secondary analyses compared dose-adjusted absolute change in mortality risk for olanzapine, quetiapine, and risperidone. RESULTS Compared with respective matched nonusers, individuals receiving haloperidol had an increased mortality risk of 3.8% (95% CI, 1.0%-6.6%; P < .01) with an NNH of 26 (95% CI, 15-99); followed by risperidone, 3.7% (95% CI, 2.2%-5.3%; P < .01) with an NNH of 27 (95% CI, 19-46); olanzapine, 2.5% (95% CI, 0.3%-4.7%; P = .02) with an NNH of 40 (95% CI, 21-312); and quetiapine, 2.0% (95% CI, 0.7%-3.3%; P < .01) with an NNH of 50 (95% CI, 30-150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%-16.0%; P < .01) with an NNH of 8 (95% CI, 6-12) for haloperidol users to 3.2% (95% CI, 1.6%-4.9%; P < .01) with an NNH of 31 (95% CI, 21-62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%-6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%-2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%-3.0%; P = .047). CONCLUSIONS AND RELEVANCE The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose.

Postpartum mood disorders

Depression is a common disorder in women of childbearing age. Many women experience depressive symptoms during the postpartum period, ranging from mild postpartum blues to significant mood disorders such as postpartum depression and postpartum psychosis. The ‘baby blues‘ are extremely common, affecting 30-75% of new mothers. This form of postpartum mood change is self-limited and requires no specific treatment other than education and support. While less common, occurring in 10-15% of births, postpartum depression has the potential for significant impact on both the health of the mother and baby. Unfortunately, affective illness in women frequently goes unrecognized and untreated. While there are effective pharmacological treatments for postpartum depression, the treatments for postpartum depression are often not utilized due to concerns about lactation. Postpartum psychosis is extremely rare, affecting one to two women per 1000 births; each case represents a true psychiatric emergency. Identifying and treating postpartum affective illness in women is critical to the health of both mother and infant. This paper reviews the literature on the diagnosis and treatment of mood disorders in the postpartum period: postpartum blues, postpartum depression and postpartum psychosis.

Risk of mortality among individual antipsychotics in patients with dementia.

OBJECTIVE The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality. The authors examined the mortality risk of individual agents to augment the limited information on individual antipsychotic risk. METHOD The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (fiscal years 1999-2008) for dementia patients age 65 and older who began outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid and its derivatives (as a nonantipsychotic comparison). The total sample included 33,604 patients, and individual drug groups were compared for 180-day mortality rates. The authors analyzed the data using multivariate models and propensity adjustments. RESULTS In covariate-adjusted intent-to-treat analyses, haloperidol was associated with the highest mortality rates (relative risk=1.54, 95% confidence interval [CI]=1.38-1.73) followed by risperidone (reference), olanzapine (relative risk=0.99, 95% CI=0.89-1.10), valproic acid and its derivatives (relative risk=0.91, 95% CI=0.78-1.06), and quetiapine (relative risk=0.73, 95% CI=0.67-0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns. The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up. CONCLUSIONS There may be differences in mortality risks among individual antipsychotic agents used for treating patients with dementia. The use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

Enhanced identification of eligibility for depression research using an electronic medical record search engine

PURPOSE Electronic medical records (EMRs) have become part of daily practice for many physicians. Attempts have been made to apply electronic search engine technology to speed EMR review. This was a prospective, observational study to compare the speed and clinical accuracy of a medical record search engine vs. manual review of the EMR. METHODS Three raters reviewed 49 cases in the EMR to screen for eligibility in a depression study using the electronic medical record search engine (EMERSE). One week later raters received a scrambled set of the same patients including 9 distractor cases, and used manual EMR review to determine eligibility. For both methods, accuracy was assessed for the original 49 cases by comparison with a gold standard rater. RESULTS Use of EMERSE resulted in considerable time savings; chart reviews using EMERSE were significantly faster than traditional manual review (p=0.03). The percent agreement of raters with the gold standard (e.g. concurrent validity) using either EMERSE or manual review was not significantly different. CONCLUSIONS Using a search engine optimized for finding clinical information in the free-text sections of the EMR can provide significant time savings while preserving clinical accuracy. The major power of this search engine is not from a more advanced and sophisticated search algorithm, but rather from a user interface designed explicitly to help users search the entire medical record in a way that protects health information.

Prevention, diagnosis, and management of postoperative delirium in older adults.

Approximately half of all operations performed in the United States are in patients greater than 65 years of age. The aging of the US population is expected to result in an increased need for surgical services among all subspecialties. Older adults represent a unique challenge to the surgeon, often presenting with multiple medical comorbidities and higher risk for postoperative complications. Despite the increasing need for surgical procedures among the elderly population, scant literature exists to address the specific perioperative needs of older adults. Among the many postoperative complications that result in increased morbidity, mortality, and health care costs, delirium represents a vital concern for surgeons. But research targeting prevention and management of postoperative delirium is limited. In this review, we highlight the available evidence for prevention and management of delirium. We also provide guidelines for optimal supportive care of the delirious surgery patient.

Predictors of suicide in patients with dementia

Assessing predictors of suicide and means of completion in patients with dementia may aid the development of interventions to reduce risk of suicide among the growing population of individuals with dementia.

Describing the relationship between cat bites and human depression using data from an electronic health record.

Data mining approaches have been increasingly applied to the electronic health record and have led to the discovery of numerous clinical associations. Recent data mining studies have suggested a potential association between cat bites and human depression. To explore this possible association in more detail we first used administrative diagnosis codes to identify patients with either depression or bites, drawn from a population of 1.3 million patients. We then conducted a manual chart review in the electronic health record of all patients with a code for a bite to accurately determine which were from cats or dogs. Overall there were 750 patients with cat bites, 1,108 with dog bites, and approximately 117,000 patients with depression. Depression was found in 41.3% of patients with cat bites and 28.7% of those with dog bites. Furthermore, 85.5% of those with both cat bites and depression were women, compared to 64.5% of those with dog bites and depression. The probability of a woman being diagnosed with depression at some point in her life if she presented to our health system with a cat bite was 47.0%, compared to 24.2% of men presenting with a similar bite. The high proportion of depression in patients who had cat bites, especially among women, suggests that screening for depression could be appropriate in patients who present to a clinical provider with a cat bite. Additionally, while no causative link is known to explain this association, there is growing evidence to suggest that the relationship between cats and human mental illness, such as depression, warrants further investigation.

Mortality Risk With the Use of Atypical Antipsychotics in Later-Life Bipolar Disorder:

Introduction: In recent years, concerns about the use of antipsychotic medications in dementia have grown. There is limited data on mortality risk of atypical antipsychotics for other psychiatric disorders of later life such as bipolar disorder. Methods: Data were derived from the national Department of Veterans Affairs registries for older patients with bipolar disorder (>65 years) with a new start of an atypical antipsychotic (risperidone, olanzapine, or quetiapine) or valproic acid and derivatives during fiscal years 2001-2008. Six-month mortality rates were compared for individual drug groups. Results: The sample included 4717 patients. The risperidone cohort had the highest mortality rate (11.8 per 100 person-years) with the quetiapine and valproic acid cohorts having the lowest (5.3 and 4.6 per 100 person-years, respectively). Various methods to adjust for baseline differences including propensity models showed similar patterns. Conclusions: Among older patients with bipolar disorder, there may be differences in mortality risks among individual antipsychotic agents.

Psychosocial Predictors of Lower Urinary Tract Symptom Bother in Black Men: The Flint Men's Health Study

PURPOSE Despite the importance of lower urinary tract symptom related bother to health related quality of life and treatment use little is known about factors contributing to perceived bother. We examined associations between several psychosocial measures and lower urinary tract symptom related bother in a population based sample of black men. MATERIALS AND METHODS In 1996, 361 black men 40 to 79 years old from Genesee County, Michigan with no history of prostate cancer/surgery provided information on lower urinary tract symptom bother and several psychosocial factors, including perceived stress, social support, stressful life events, and self-rated physical and emotional health. Associations between these factors and perceived bother were examined, controlling for age and lower urinary tract symptom severity. RESULTS Overall 39.3% of men reported moderate/severe lower urinary tract symptom related bother. Men with poor emotional health and low social support were 2.25 (95% CI 1.05, 4.85) and 2.89 (95% CI 1.14, 7.35) times more likely to report moderate and severe bother, respectively. No other psychosocial factors significantly impacted bother after adjusting for age and lower urinary tract symptom severity. CONCLUSIONS In this population based study of black men poor emotional health and low social support were significantly associated with moderate/severe lower urinary tract symptom related bother after adjusting for age and lower urinary tract symptom severity, supporting the notion that urinary bother measures may capture somatic and psychological distress. These findings suggest that treating lower urinary tract symptoms alone may not completely ameliorate urinary bother if underlying emotional health and social support problems are not addressed. Further studies are warranted in racially diverse populations.

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

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.