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ABSTRACT: 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.
American Journal of Psychiatry 05/2013; · 12.54 Impact Factor
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Helen C Kales,
Donald E Nease,
Jo Anne Sirey,
Kara Zivin,
Hyungjin Myra Kim,
Janet Kavanagh,
Shana Lynn,
Claire Chiang,
Harold W Neighbors,
Marcia Valenstein,
Frederic C Blow
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ABSTRACT: OBJECTIVE:: Although antidepressants are an effective treatment for later-life depression, older patients often choose not to initiate or to discontinue medication treatment prematurely. Although racial differences in depression treatment preferences have been reported, little is known about racial differences in antidepressant medication adherence among older patients. DESIGN:: Prospective, observational study comparing antidepressant adherence for older African American and white primary care patients. PARTICIPANTS:: A total of 188 subjects age 60 and older, diagnosed with clinically significant depression with a new recommendation for antidepressant treatment by their primary care physician. MEASUREMENT:: Study participants were assessed at study entry and at the 4-month follow-up (encompassing the acute treatment phase). Depression medication adherence was based on a well-validated self-report measure. RESULTS:: At the 4-month follow-up, 61.2% of subjects reported that they were adherent to their antidepressant medication. In unadjusted and two of the three adjusted analyses, African American subjects (n = 82) had significantly lower rates of 4-month antidepressant adherence than white subjects (n = 106). African American women had the lowest adherence rates (44.4%) followed by African American men (56.8%), white men (65.3%), and white women (73.7%). In logistic regression models controlling for demographic, illness, and functional status variables, significant differences persisted between African American women and white women in reported 4-month antidepressant adherence (OR: 3.58, 95% CI: 1.27-10.07, Wald χ = 2.42, df = 1, p <0.02). CONCLUSIONS:: The results demonstrate racial and gender differences in antidepressant adherence in older adults. Depression treatment interventions for older adults should take into account the potential impact of race and gender on adherence to prescribed medications.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 10/2012; · 3.35 Impact Factor
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ABSTRACT: Substantial literature documents excess and early mortality among individuals with serious mental illness, but there are relatively few data about mortality and depression.
During fiscal year 2007, data from the U.S. Department of Veterans Affairs and the National Death Index were used to calculate mean age of death and years of potential life lost (YPLL) associated with 13 causes of death among veterans with (N=701,659) or without (N=4,245,193) depression.
Compared with nondepressed patients, depressed patients died younger (71.1 versus 75.9) and had more YPLL (13.4 versus 10.2) as a result of both natural and unnatural causes. Depending on the cause of death, depressed patients died between 2.5 and 8.7 years earlier and had 1.5 to 6.1 YPLL compared with nondepressed patients.
These findings have important implications for clinical practice, given that improved quality of care may be needed to reduce early mortality among depressed VA patients.
Psychiatric services (Washington, D.C.) 08/2012; 63(8):823-6. · 2.81 Impact Factor
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American Journal of Psychiatry 06/2012; 169(6):664-5. · 12.54 Impact Factor
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ABSTRACT: 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.
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.
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.
Among older patients with bipolar disorder, there may be differences in mortality risks among individual antipsychotic agents.
Journal of Geriatric Psychiatry and Neurology 03/2012; 25(1):29-36. · 3.07 Impact Factor
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ABSTRACT: : Older adults in the VA Healthcare System may have an increased risk for depression than those in the general population. These factors may also be associated with the likelihood of receiving depression treatment. This study examined the associations between sociodemographic characteristics, psychiatric comorbidities, and medical comorbidities and the receipt of depression treatment among depressed older adults in the VA.
: Secondary analysis of data obtained from the VA's National Registry for Depression, a linkage of several administrative data sources with detailed services and pharmacy data for all VA patients diagnosed with depression.
: VA healthcare system.
: The sample included 147,631 VA patients who were at least 50 years old and received a new diagnosis of depression in FY08.
: The associations between the depression treatment conditions (antidepressants, psychotherapy, both, and none) as outcome variables and sociodemographic characteristics, psychiatric comorbidities, and medical comorbidities as independent variables were assessed using χ tests and multinomial logistic regression analysis.
: Approximately one-third (35.9%) of the depressed older adults did not receive any treatment. The odds receiving depression treatment decreased with increasing age. Those who were white, female and married were more likely to receive antidepressants, while those who were male of minority race/ethnicity, and unmarried were more likely to receive psychotherapy. Medical comorbidities and psychiatric comorbidities were also associated with the type of depression treatment received.
: Many depressed older adults may have limited or no treatment. Future outreach and intervention efforts should be targeted toward this vulnerable population.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2012; 20(3):228-38. · 3.35 Impact Factor
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ABSTRACT: 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.
This national, retrospective, cohort study used data from the Department of Veterans Affairs (fiscal years 2001-2005). The sample included patients ≥60 years old diagnosed with dementia (N = 294,952), of which 241 committed suicide. Potential predictors of suicide were identified using logistic regression. Suicide methods are also reported.
Increased risk of suicide was associated with white race (OR: 2.4, 95% CI: 1.2, 4.8), depression (OR: 2.0, 95% CI: 1.5, 2.9), a history of inpatient psychiatric hospitalizations (OR: 2.3, 95% CI: 1.5, 3.5), and prescription fills of antidepressants (OR: 2.1, 95% CI: 1.6, 2.8) or anxiolytics (OR: 2.0, 95% CI: 1.5, 2.7). Nursing home admission was associated with lower suicide risk (OR: 0.3, 95% CI: 0.1, 0.8). Severity of medical comorbidity did not affect risk of suicide. Sensitivity analysis indicated that the majority of suicides occurred in those who were newly diagnosed with dementia. Firearms were the most common method of suicide (73%) used.
Given the higher rate of suicide in those receiving treatment for psychiatric symptoms and the high proportion that died using firearms, closer monitoring and assessment of gun access may be an important part of initial treatment planning for older male patients with dementia, particularly those with symptoms of depression or anxiety.
Alzheimer's & dementia: the journal of the Alzheimer's Association 11/2011; 7(6):567-73. · 5.90 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
American Journal of Psychiatry 10/2011; 169(1):71-9. · 12.54 Impact Factor
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ABSTRACT: This study aimed to evaluate factors associated with the selection of pharmacological treatments often given as first-line treatments to elderly patients with neuropsychiatric symptoms associated with dementia. It also evaluated patterns of medication usage over time in the year preceding and three years after the U.S. Food and Drug Administration issued a black box warning for antipsychotic usage.
A retrospective cohort consisted of 19,517 Veterans Affairs patients with diagnosed dementia and a new outpatient start with an antipsychotic agent (haloperidol, olanzapine, quetiapine, or risperidone) or valproic acid and its derivatives between May 1, 2004, and September 30, 2008. Patient and facility characteristics were examined for their association with the new starts of these medications.
Trends in the rate of fills for psychotropic medications varied, with yearly increases in the use of quetiapine, haloperidol, and valproic acid and decreasing use of olanzapine and risperidone. Predictors of haloperidol use included a new start in nonpsychiatric settings, prior benzodiazepine use, and any prior-year hospitalization. Anxiety disorder and major depression were predictive of not receiving haloperidol. Parkinson's disease was predictive of quetiapine use, whereas bipolar disorder was predictive of valproic acid use. Older age was predictive of use of antipsychotics rather than valproic acid. Urban facilities were less likely to use olanzapine, and significant regional variations were seen.
Important patient and facility characteristics were associated with initiating different psychotropic agents among elderly dementia patients. In addition, the rate of use and the factors predictive of use varied across the study years.
Psychiatric services (Washington, D.C.) 10/2011; 62(10):1207-14. · 2.81 Impact Factor
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ABSTRACT: Antipsychotic (AP) use is common in Parkinson disease (PD), but APs can worsen parkinsonism, evidence for efficacy is limited, and use in patients with dementia increases mortality.
To examine the frequency and characteristics, including changes over time, of AP use in a large cohort of patients with PD.
Using Veterans Affairs data from fiscal year (FY) 2008, rates and predictors of AP prescribing were determined for patients with PD and psychosis stratified by dementia status (N = 2597) and a comparison group of patients with dementia and psychosis without PD (N = 6907). Fiscal year 2008 and FY2002 data were compared to examine changes in AP prescribing over time.
Department of Veterans Affairs outpatient facilities.
Outpatients with PD and psychosis and outpatients without PD with dementia and psychosis, all receiving care at Veterans Affairs facilities in FY2002 and FY2008.
Antipsychotic prescribing, including overall, class, and specific medications.
In FY2008, 50% of patients with PD having a diagnosis of psychosis were prescribed an AP. Among treated patients, the atypical AP quetiapine was most frequently prescribed (66%), but approximately 30% received high-potency APs. Clozapine was rarely prescribed (<2%). In multivariate models, diagnoses of PD and dementia were associated with AP use. Comparing FY2008 with FY2002, AP use in PD was unchanged, with decreases in risperidone and olanzapine use offset by an increase in quetiapine prescribing and the introduction of aripiprazole.
Half of the patients with PD and psychosis receive APs, not uncommonly high-potency agents associated with worsening parkinsonism, and frequency of use has been unchanged since the "black box" warning for AP use in patients with dementia was issued. Recent trends are a shift to quetiapine use and the common use of aripiprazole. As psychosis and dementia are frequently comorbid in PD, safety risks associated with AP use in this population need to be assessed.
Archives of neurology 07/2011; 68(7):899-904. · 6.31 Impact Factor
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Helen C Kales,
Kara Zivin,
Hyungjin Myra Kim,
Marcia Valenstein,
Claire Chiang,
Rosalinda V Ignacio,
Rosalindo Ignacio,
Dara Ganoczy,
Francesca Cunningham,
Lon S Schneider,
Frederic C Blow
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ABSTRACT: 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.
To examine changes in atypical and conventional antipsychotic use in outpatients with dementia from 1999 through 2007.
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).
Patients aged 65 years or older with dementia (n = 254 564).
Outpatient antipsychotic use (percentage of patients, percentage of quarterly change, and difference between consecutive study periods).
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).
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.
Archives of general psychiatry 02/2011; 68(2):190-7. · 12.26 Impact Factor
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ABSTRACT: Using a case history to illustrate key points, this article (1) highlights depression criteria, prevalence, and later-life depression presentations; (2) discusses factors contributing to later-life depression; (3) reviews the interplay between heart failure and later-life depression; and (4) suggests screening and treatment recommendations for depression in patients with heart failure.
Heart Failure Clinics 01/2011; 7(1):47-58.
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ABSTRACT: To examine the intensity of monitoring received by important patient subgroups during high-risk periods (the 12 weeks after psychiatric hospitalization and after new antidepressant starts).
Retrospective secondary analysis of data from the Veterans Affairs (VA) National Registry for Depression using patients aged 65 and older receiving depression treatment from 1999 to 2004.
VA healthcare system.
VA patients in depression treatment between April 1, 1999, and September 30, 2004, who had psychiatric inpatient stays (n=73,137) or new antidepressant starts (n=421,536).
The relationship between the number of outpatient visits for each group and patient characteristics in the 12-week period after psychiatric hospitalizations and antidepressant starts.
The characteristic associated with significantly lower rates of monitoring for both high-risk treatment periods was aged 65 and older. White race and living in the south or northeast were also associated with significantly lower rates of monitoring after new antidepressant starts and inpatient stays, respectively. Substance abuse disorders were associated with greater monitoring after both types of depression events but did not seem to interact with other patient characteristics in determining levels of monitoring.
VA patients who are older, white, and living in the south or northeast receive less-intensive monitoring during high-risk treatment periods for suicide. This is of concern, given that older patients appear to be at higher risk for suicide, particularly after inpatient stays, and may need particular attention during this time frame. Adapted interventions and proactive outreach may be needed that target this patient group.
Journal of the American Geriatrics Society 05/2010; 58(5):908-13. · 3.74 Impact Factor
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Helen C Kales
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 02/2010; 18(4):277-80. · 3.35 Impact Factor
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ABSTRACT: To examine concerns that vulnerable populations, such as depressed or cognitively impaired beneficiaries would have challenges accessing Part D coverage.
Logistic regression analysis was used to assess whether elderly Medicare beneficiaries with depression or cognitive impairment differentially planned to and actually signed up for Part D.
2004 and 2006 data from the Health and Retirement Study (HRS) were used, including a subsample that completed the Prescription Drug Study (PDS) in 2005.
Nine thousand five hundred ninety-three HRS respondents and 3,567 PDS respondents.
The outcome variables of interest were planned and actual enrollment in Part D. The independent variables were depression and cognitive impairment status. The analyses were adjusted using clinical and demographic predictors including age, sex, race or ethnicity, educational attainment, net worth, marital status, health status, number of health conditions being treated with prescription medications, and presence of a caregiver.
Although having depression or cognitive impairment was associated with a higher likelihood of planning to and actually signing up for Part D in unadjusted analyses, in adjusted analyses, having depression or cognitive impairment was not significantly associated with whether Medicare beneficiaries planned to enroll in or actually enrolled in Part D.
Vulnerable Medicare beneficiaries with depression or cognitive impairment were able to access Part D benefits to the same extent as nonvulnerable beneficiaries. More research is needed to determine how well Part D meets the needs of these populations.
Journal of the American Geriatrics Society 07/2009; 57(8):1433-40. · 3.74 Impact Factor
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ABSTRACT: Older patients may regard some medications, particularly psychotropic medications, as discretionary compared with what they perceive as more "essential " nonpsychiatric medications. Patients' concerns about psychotropic medication costs under Medicare Part D may reinforce these impressions.
The authors examined which Medicare prescription drug plans (PDPs) would be least expensive for beneficiaries considering the costs of 1) all medications; and 2) only nonpsychiatric medications. Setting: The authors collected data from the PDP online comparison tool provided by the Centers for Medicare and Medicaid Services (CMS).
Hypothetical Medicare beneficiaries.
The authors examined four clinical scenarios from older outpatients with both chronic medical and psychiatric conditions (including psychosis, bipolar disorder, depression, and dementia with behavioral disturbances).
The authors examined data from all 160 plans available in CMS PDP regions in May 2007. There were frequent discrepancies in the least expensive PDPs within region, depending on considering the costs of all medications, or just nonpsychiatric medications. In the clinical scenarios, patients selecting a PDP based on nonpsychiatric medications alone would pick an unnecessarily more expensive plan 74%-100% of the time (when they took any brand name medication), suggesting that excluding psychiatric medications from PDP choices may be excessively costly. However, brand name psychotropic medications significantly increased the costs of the least expensive plans. The latter finding might persuade patients to avoid taking needed psychiatric medication due to cost.
This research highlights the complexity that patients with psychiatric and cognitive disorders face when choosing a Medicare PDP. Policymakers and clinicians should be aware of the tradeoffs that beneficiaries with psychiatric disorders face when making PDP plan choices.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 09/2008; 16(8):674-85. · 3.35 Impact Factor
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Helen C Kales
Evidence-based mental health 06/2008; 11(2):54.
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ABSTRACT: Depression in older adults has been detected, diagnosed and treated more frequently in recent years. However, substantial gaps in effective treatment remain. Adherence to depression treatment can be viewed as the 'next frontier' in the treatment of late-life depression. Using the Theory of Reasoned Action, a model of health behaviours, this paper conceptualizes and reviews the current evidence for key patient-level factors associated with depression treatment adherence among older adults. We categorize these factors according to how their impact on adherence might be affected by specialized treatment approaches or interventions as: (i) modifiable; (ii) potentially modifiable; and (iii) non-modifiable. Based on current evidence, modifiable factors associated with depression treatment adherence include patient attitudes, beliefs and social norms. Patient attitudes include perceptions of the effectiveness of depression treatment, preferences for the type of depression treatment and concepts regarding the aetiology of depression (e.g. resistance to viewing depression as a medical illness). There is also evidence from the literature that spiritual and religious beliefs may be important determinants of adherence to depression care. Social norms such as the impact of caregiver agreement with treatment recommendations and stigma may also affect adherence to depression treatment. Other factors may be less modifiable per se, but they may have an impact on adherence that is potentially modifiable by specialized interventions. Based upon a review of the current literature, potentially modifiable factors associated with adherence to depression treatment include co-morbid anxiety, substance use, cognitive status, polypharmacy and medical co-morbidity, social support and the cost of treatment. Finally, non-modifiable factors include patient gender and race. Importantly, non-modifiable factors may interact with modifiable factors to affect health behavioural intent (e.g. race and spiritual beliefs). Thus, adherence to depression treatment in older adults is associated with multiple factors. Strategies to improve patient adherence need to be multidimensional, including consideration of age-related cognitive and co-morbidity factors, environmental and social factors, functional status and belief systems. Evidence-based interventions involving greater patient, caregiver, provider and public health education should be developed to decrease stigma, negative attitudes and other modifiable barriers to detection, diagnosis, treatment and adherence to depression treatment. These interventions should also be tailored to the individual as well as to the treatment setting. While important progress has been made in increasing detection of depression in older adults, greater focus now needs to be placed on treatment engagement and continuation of improvements in quality of life, reducing suffering and achieving better outcomes.
Drugs & Aging 02/2008; 25(7):559-71. · 2.67 Impact Factor
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The journal of the American Academy of Psychiatry and the Law 02/2008; 36(1):6-9. · 0.93 Impact Factor
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ABSTRACT: Few studies have evaluated medication adherence among older vs younger individuals with bipolar disorder (BPD). We compared adherence with antipsychotic medication among older (age 60 and older) and younger individuals using a large case registry (n = 73,964).
Adherence was evaluated using the medication possession ratio (MPR) for patients receiving antipsychotic medication.
Twenty six thousand five hundred and thirty younger individuals (mean age 46.9) and 6,461 older individuals (mean age 69.2) were prescribed antipsychotic medication. Among older individuals, 61.0% (n = 3,350) were fully adherent, while 19.0% (n = 1,043) were partially adherent and 20.0% (n = 1,098) were non-adherent. Among younger individuals, 49.5% (n = 10,644) were fully adherent, while 21.8% (n = 4,680) were partially adherent, and 28.7% (n = 6,170) were non-adherent. As with younger patients, comorbid substance abuse and homelessness predicted non-adherence among older patients with BPD.
Older individuals with BPD were more adherent with antipsychotic medications compared to younger individuals. However, a substantial proportion (approximately 39%) of older patients with BPD still have difficulties with adherence.
International Journal of Geriatric Psychiatry 11/2007; 22(10):992-8. · 2.42 Impact Factor
