[Show abstract][Hide abstract] ABSTRACT: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the short-term mortality in a population-based cohort of elderly people in British Columbia who were prescribed conventional and atypical antipsychotic medications.
We used linked health care utilization data of all BC residents to identify a cohort of people aged 65 years and older who began taking antipsychotic medications between January 1996 and December 2004 and were free of cancer. We compared the 180-day all-cause mortality between residents taking conventional antipsychotic medications and those taking atypical antipsychotic medications.
Of 37 241 elderly people in the study cohort, 12 882 were prescribed a conventional antipsychotic medication and 24 359 an atypical formulation. Within the first 180 days of use, 1822 patients (14.1%) in the conventional drug group died, compared with 2337 (9.6%) in the atypical drug group (mortality ratio 1.47, 95% confidence interval [CI] 1.39-1.56). Multivariable adjustment resulted in a 180-day mortality ratio of 1.32 (1.23-1.42). In comparison with risperidone, haloperidol was associated with the greatest increase in mortality (mortality ratio 2.14, 95% CI 1.86-2.45) and loxapine the lowest (mortality ratio 1.29, 95% CI 1.19-1.40). The greatest increase in mortality occurred among people taking higher (above median) doses of conventional antipsychotic medications (mortality ratio 1.67, 95% CI 1.50-1.86) and during the first 40 days after the start of drug therapy (mortality ratio 1.60, 95% CI 1.42-1.80). Results were confirmed in propensity score analyses and instrumental variable estimation, minimizing residual confounding.
Among elderly patients, the risk of death associated with conventional antipsychotic medications is comparable to and possibly greater than the risk of death associated with atypical antipsychotic medications. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients.
Preview · Article · Mar 2007 · Canadian Medical Association Journal
[Show abstract][Hide abstract] ABSTRACT: This study evaluated Medicaid's prior-authorization policies restricting the prescribing of antidepressant medications for children.
Medicaid program prior-authorization policies for antidepressant medications were obtained for all available states. All criteria needed for authorization were recorded, with a focus on policies that applied specifically to children.
Data from 49 states and the District of Columbia revealed that 30 states (60%) required prior authorization for antidepressants, of which eight (27%) made specific provisions for children. These provisions varied across states. In most states fluoxetine could be prescribed for children with minimal restrictions, and two states had prior-authorization policies that strongly encouraged pediatric patients to use fluoxetine. State policies regarding other selective serotonin reuptake inhibitors varied widely.
Although relatively few states included provisions for children in prior-authorization requirements for antidepressants, in states that did, the policies implemented varied widely. These findings raise important questions about the rational development of prescription drug reimbursement policy.
Preview · Article · Feb 2007 · Psychiatric Services
[Show abstract][Hide abstract] ABSTRACT: The results of recent community epidemiological research are reviewed, documenting that major depressive disorder (MDD) is a highly prevalent, persistent, and often seriously impairing disorder, and that bipolar disorder (BPD) is less prevalent but more persistent and more impairing than MDD. The higher persistence and severity of BPD results in a substantial proportion of all seriously impairing depressive episodes being due to threshold or subthreshold BPD rather than to MDD. Although the percentage of people with mood disorders in treatment has increased substantially since the early 1990s, a majority of cases remain either untreated or undertreated. An especially serious concern is the misdiagnosis of depressive episodes due to BPD as due to MDD because the majority of depression treatment involves medication provided by primary care doctors in the absence of psychotherapy. The article closes with a discussion of future directions for research.
No preview · Article · Feb 2007 · Annual Review of Clinical Psychology
[Show abstract][Hide abstract] ABSTRACT: This study compared the prevalence of depression and the determinants of mental health service use in Canada and the United States.
The study used data from preliminary analyses of the 2003 Joint Canada/United States Survey of Health, which measured Canadian (N=3,505) and United States (N=5,183) resident ratings of health and health care services. Cross-national comparisons were made for the 12-month prevalence of DSM-IV major depression, 12-month service use for mental health reasons according to the type of professional seen, and determinants of service use.
The rates of depression were similar in Canada (8.2%) and the United States (8.7%). However, U.S. respondents without medical insurance were twice as likely as Canadian respondents and U.S. respondents with medical insurance to meet the criteria for depression. Rates of mental health service use did not differ between Canada (10.1%) and the United States (10.6%). In the United States, medical insurance was not a determinant factor of service use. However, U.S. respondents with no medical insurance were more likely than the other two groups to report an unmet need. Also, among those with depression, U.S. respondents with no medical insurance were less likely to use any type of mental health service (36.5%) than U.S. respondents with medical insurance (55.7%) and Canadians (55.7%). Further, a positive correlation between a mental health need and service use was observed in Canada but not for those without medical insurance in the United States.
There was no difference in the prevalence of depression and mental health service use between Canada and the United States. Among those with depression, however, disparities in treatment seeking were found to be associated with medical insurance in the United States. Both Canada and the United States need to improve access to health services for those with mental disorders, and special attention is needed for those without medical insurance in the United States.
Full-text · Article · Feb 2007 · Psychiatric Services
[Show abstract][Hide abstract] ABSTRACT: Although outreach and enhanced treatment interventions improve depression outcomes, uptake has been poor in part because purchasers lack information on their return on investment.
To estimate the costs and benefits of enhanced depression care for workers from the societal and employer-purchaser perspectives.
Cost-effectiveness and cost-benefit analyses using state-transition Markov models. Simulated movements between health states were based on probabilities drawn from the clinical literature.
Hypothetical cohort of 40-year-old workers. Intervention Enhanced depression care consisting of a depression screen and care management for those depressed vs usual care.
Our base-case cost-effectiveness analysis was from the societal perspective; costs and quality-adjusted life-years were used to compute the incremental cost-effectiveness of the intervention relative to usual care. A secondary cost-benefit analysis from the employer's perspective tracked monetary costs and monetary benefits accruing to employers during a 5-year time horizon.
From the societal perspective, screening and depression care management for workers result in an incremental cost-effectiveness ratio of $19 976 per quality-adjusted life-year relative to usual care. These results are consistent with recent primary care effectiveness trials and within the range for medical interventions usually covered by employer-sponsored insurance. From the employer's perspective, enhanced depression care yields a net cumulative benefit of $2895 after 5 years. In 1-way and probabilistic sensitivity analyses, these findings were robust to a variety of assumptions.
If these results can be replicated in effectiveness trials directly assessing effects on work outcomes, they suggest that enhanced treatment quality programs for depression are cost-beneficial to purchasers.
Preview · Article · Jan 2007 · Archives of General Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Behavioral disturbances associated with dementia are common and burdensome. Although no psychotropic medications are currently approved by the US Food and Drug Administration (FDA) to treat such behavioral symptoms, a variety of drug classes are commonly used for these purposes. Atypical antipsychotic medications may be somewhat effective and are generally considered the pharmacologic treatments of choice; however "black box" warnings have recently been added to their labels by the FDA, warning of significantly increased risks of short-term mortality. Older conventional antipsychotic medications may also be somewhat effective but appear to pose risks that can be at least as great as those of the newer atypical drugs. Although antidepressants, benzodiazepines, mood stabilizers, acetylcholinesterase inhibitors, and N-methyl-D-aspartate (NMDA) receptor antagonists may be considered, particularly in patients with specific types of symptomatology, even less is known about their effectiveness and safety. Also, although various psychotropic medications used for behavioral disturbances in dementia patients may be somewhat effective, they have been increasingly associated with important safety risks.
No preview · Article · Dec 2006 · Current Neurology and Neuroscience Reports
[Show abstract][Hide abstract] ABSTRACT: To simultaneously assess the short-term reduction in risk of gastrointestinal (GI) complications and increase in risk of acute myocardial infarction (MI) by celecoxib compared with rofecoxib and several nonselective nonsteroidal antiinflammatory drugs (NSAIDs) using instrumental variable analysis.
A population of 49,711 Medicare beneficiaries ages 65 years and older who initiated nonselective NSAID or selective cyclooxygenase 2 inhibitor therapy between January 1, 1999, and December 31, 2002, was identified. The increase in risk of GI complications and MI within 180 days after initiation of NSAID (rofecoxib, diclofenac, ibuprofen, and naproxen compared with celecoxib) therapy was assessed using instrumental variable analysis.
Compared with nonselective NSAIDs, celecoxib reduced the risk of GI complications by 1.4 per 100 users but increased the risk of MI by 0.3 per 100 users. Rofecoxib decreased GI complications by 1.1 per 100 users and increased the risk of MI by 0.3 per 100 users. Using celecoxib as the reference exposure showed an increase in the MI risk for rofecoxib (risk difference [RD] 1.40, 95% confidence interval [95% CI] -0.20, 3.01) and diclofenac (RD 6.07, 95% CI -0.02, 12.15). The RD for naproxen as well as its upper 95% CI was the lowest of all NSAIDs (RD -0.30, 95% CI -2.74, 2.14) and there was no significant difference in GI complication rates among all NSAIDs.
In this instrumental variable analysis, diclofenac and rofecoxib had the least favorable benefit-risk balance among NSAIDs in older adults.
Preview · Article · Nov 2006 · Arthritis & Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Research on the workplace costs of mood disorders has focused largely on major depressive episodes. Bipolar disorder has been overlooked both because of the failure to distinguish between major depressive disorder and bipolar disorder and by the failure to evaluate the workplace costs of mania/hypomania.
The National Comorbidity Survey Replication assessed major depressive disorder and bipolar disorder with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) and work impairment with the WHO Health and Work Performance Questionnaire. A regression analysis of major depressive disorder and bipolar disorder predicting Health and Work Performance Questionnaire scores among 3,378 workers was used to estimate the workplace costs of mood disorders.
A total of 1.1% of the workers met CIDI criteria for 12-month bipolar disorder (I or II), and 6.4% meet criteria for 12-month major depressive disorder. Bipolar disorder was associated with 65.5 and major depressive disorder with 27.2 lost workdays per ill worker per year. Subgroup analysis showed that the higher work loss associated with bipolar disorder than with major depressive disorder was due to more severe and persistent depressive episodes in those with bipolar disorder than in those with major depressive disorder rather than to stronger effects of mania/hypomania than depression.
Employer interest in workplace costs of mood disorders should be broadened beyond major depressive disorder to include bipolar disorder. Effectiveness trials are needed to study the return on employer investment of coordinated programs for workplace screening and treatment of bipolar disorder and major depressive disorder.
Full-text · Article · Oct 2006 · American Journal of Psychiatry
[Show abstract][Hide abstract] ABSTRACT: This study described the rate and adequacy of mental health service use among participants in the Mexico National Comorbidity Survey and the correlates of any 12-month treatment and of adequate treatment.
The authors conducted face-to-face household surveys of a probability sample of individuals ages 18 to 65 years in the noninstitutionalized population living in urban areas of Mexico from 2001 to 2002. The use of mental health services and 12-month DSM-IV disorders was assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview. The rates and correlates of any service use and the adequacy of treatment were identified in logistic regression analyses, taking into account the complex sample design and weighting process.
The data reported here were based on 2,362 interviews. Fewer than one in five respondents with any psychiatric disorder during the last 12 months used any service during the prior year. The rates of service use by those with mood disorders were somewhat higher. About one in every two respondents who used services received minimally adequate care.
The authors found large unmet needs for mental health services among those with psychiatric disorders. Those with mental illness and those who deliver or seek to improve mental health care in Mexico face enormous challenges.
Preview · Article · Sep 2006 · American Journal of Psychiatry
[Show abstract][Hide abstract] ABSTRACT: General medical (GM) treatments for mental health disorders are less likely than specialty mental health (SMH) treatments to be adequate. We explored whether differences in the clinical characteristics of patients treated in each sector (GM-only or SMH-only) or in both sectors (GM+SMH) may help to explain this finding.
We analyzed data from the National Comorbidity Survey Replication (NCS-R), a nationally representative household survey of 5692 English-speaking adult household residents that was carried out in 2001-2003. The NCS-R used a fully structured diagnostic interview to assess DSM-IV disorders, including mood, anxiety, impulse control and substance use disorders. We classified disorders in terms of a three-category severity gradient (serious, moderate and mild) based on information about clinically significant distress and role impairment. We collected self-report data on chronic physical conditions, sociodemographics and type of treatment received for emotional and substance use problems in the 12 months before the interview.
Patients who received GM+SMH treatment had more severe mental disorders and a higher prevalence of mood and anxiety disorders than patients who received treatment in only one of the two sectors. Patients seen in the GM-only and GM+SMH sectors had more chronic physical conditions than patients seen in the SMH-only sector.
Patient characteristics may partially explain the lower intensity and adequacy of GM treatment.
Preview · Article · Sep 2006 · General Hospital Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Observational studies have found beneficial effects of lipid-lowering drugs on diverse outcomes, including venous thromboembolism, hip fracture, dementia, and all-cause mortality. Selective use of these drugs in frail people may confound these relationships.
We measured 1-year mortality in two cohorts of New Jersey residents, aged 65-99 years, enrolled in state-sponsored drug benefits programs: 112,463 persons hospitalized during the years 1991-1994 and 106,838 nonhospitalized enrollees. Use of lipid-lowering drugs and other medications, as well as diagnoses, were evaluated before follow-up.
In age- and sex-adjusted analyses, users of lipid-lowering drugs had a 43% reduced death rate relative to nonusers among hospitalized enrollees and a 56% reduction in the nonhospitalized sample. Available markers of frailty and comorbidity predicted decreased use of these drugs. Control for the propensity to use lipid-lowering drugs attenuated but did not eliminate these effects. After such adjustment, users had a 30% reduction in death rate (95% confidence interval [CI]: 25%-35%) among hospitalized enrollees and a 41% reduction (95% CI: 35%-47%) in the nonhospitalized sample. Unmeasured frailty associated with a 26%-33% reduced odds of receiving lipid-lowering therapy could explain this effect.
Frailty and comorbidity that influence use of preventive therapies can substantially confound apparent benefits of lipid-lowering drugs on outcomes.
No preview · Article · Sep 2006 · Journal of Clinical Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Redesigning the fragmented U.S. mental health care system requires knowing how service sectors share responsibility for individuals' mental health needs.
Twelve-month DSM-IV mental disorders and their severity were assessed in respondents ages 15-54 from the National Comorbidity Survey (NCS) in 1990-1992 (N=5,388) and the NCS Replication in 2001-2003 (N=4,319). Six profiles involving potentially multiple service sectors were defined, including those in which pharmacotherapy plus psychotherapy (psychiatry profile, general medical with other mental health specialty profile), single modalities (general medical only profile, other mental health specialty only profile), or neither modality (human services only profile, complementary/alternative medicine only profile) could potentially have been received. The use of profiles was compared between surveys.
The general medical only profile experienced the largest proportional increase (153%) between surveys and is now the most common profile. The psychiatry profile also increased (29%), as did the general medical with other mental health specialty profile (72%). The other mental health specialty only (-73%), the complementary/alternative medicine only (-132%), and the human services only (-137%) profiles all decreased in use. The elderly, women, minorities, the less educated, and rural dwellers were less likely to use profiles capable of delivering pharmacotherapies and/or psychotherapies.
How service sectors share responsibility for peoples' mental health care is changing, with more care falling to general medical providers rather than specialists. Efforts are required to ensure that people who would benefit have access to the necessary treatment modalities.
Full-text · Article · Aug 2006 · American Journal of Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Postmarketing observational studies of the safety and effectiveness of prescription medications are critically important but fraught with methodological problems. The data sources available for such research often lack information on indications and other important confounders for the drug exposure under study. Instrumental variable methods have been proposed as a potential approach to control confounding by indication in nonexperimental studies of treatment effects; however, good instruments are hard to find.
We propose an instrument for use in pharmacoepidemiology that is based on a time-varying estimate of the prescribing physician's preference for one drug relative to a competing therapy. The use of this instrument is illustrated in a study comparing the effect of exposure to COX-2 inhibitors with nonselective, nonsteroidal antiinflammatory medications on gastrointestinal complications.
Using conventional multivariable regression adjusting for 17 potential confounders, we found no protective effect due to COX-2 use within 120 days from the initial exposure (risk difference = -0.06 per 100 patients; 95% confidence interval = -0.26 to 0.14). However, the proposed instrumental variable method attributed a protective effect to COX-2 exposure (-1.31 per 100 patients; -2.42 to -0.20) compatible with randomized trial results (-0.65 per 100 patients; -1.08 to -0.22).
The instrumental variable method that we have proposed appears to have substantially reduced the bias due to unobserved confounding. However, more work needs to be done to understand the sensitivity of this approach to possible violations of the instrumental variable assumptions.
[Show abstract][Hide abstract] ABSTRACT: Health state preferences can be a crucial component of cost-effectiveness analyses, but off-the-shelf health state utilities specifically for older people are not available.
Among participants in PROSPER, a trial of pravastatin in patients>70 years, the authors assessed utilities for the health states that were relevant for the trial's cost-utility analysis. Subjects and
The authors cross-sectionally administered the Health Utilities Index, Mark 3 (HUI) to all PROSPER participants to assess each patient's health state at the time of interview; they then used the scale's multiattribute utility function to estimate the resulting utilities. The population was then stratified into 3 health states, and the mean utility function for each was calculated: recent myocardial infarction (MI, within 3 months), previous MI (>3 months), or no prior MI. Linear and logistic regression were used to control for potential demographic and clinical characteristics.
Of the 5804 patients enrolled in the trial, 4677 were administered the HUI instrument. The likelihood of having a complete HUI response set decreased with higher age (P<0.001) but not with the other variables studied. A complete utility score could be calculated for 3390 participants. Of these, 2755 (81.3%) had no history of MI, 546 (16.1%) had an MI>3 months previously, and 89 (2.6%) had an MI within 3 months. The mean (median) utilities were virtually identical for these states: 0.75 (0.84), 0.74 (0.84), and 0.74 (0.84), respectively. From multivariate analyses, utilities decreased with higher age and the presence of several other comorbidities (diabetes, stroke, peripheral vascular disease); women had lower utilities than men (all P<0.01).
In this large implementation of the HUI in elderly patients, the instrument did not detect any differences in estimated utilities related to having a MI. Potential causes of nondiscrimination for MI include the possibility that competing comorbidities may reduce the impact of MI on quality of life in this age group, as well as the possibility that a standard instrument derived from and validated in younger populations may not perform as well in elderly people.
No preview · Article · May 2006 · Medical Decision Making
[Show abstract][Hide abstract] ABSTRACT: To examine patterns of chronic opioid use in selected groups with arthritis and low back pain and compare them with patterns among persons with ischemic heart disease.
The study database consisted of Medicare beneficiaries who were enrolled in a drug benefit program for low-to-moderate income Pennsylvania residents. We identified selected patients who had a diagnosis of rheumatoid arthritis, osteoarthritis, chronic low back pain, or ischemic heart disease since 1995. Chronic opioid use, defined as at least six 30-day prescriptions in a year, was the endpoint of interest. We examined the proportion of patients meeting this definition during the period 1996-2001 and determined predictors based on multivariable Cox proportional hazards models.
Four percent of subjects with rheumatoid arthritis used opioids chronically in 2001, compared with <1% in each of the other groups. There was no increase in the chronic use of opioids over the 6-year study period. Low-potency opioids were the most commonly prescribed preparations for chronic users from all patient groups. The prior use of medicines for psychiatric illness, including benzodiazepines or barbiturates, was associated with chronic prescription opioid use across all diagnoses. However, subjects with a prior diagnosis of psychiatric illness were less likely to receive chronic opioids.
Chronic opioid use is relatively uncommon, even among older individuals with arthritis or low back pain. The proportion of these individuals receiving such medicines has not increased in the late 1990s. There seems to be a complex relationship between psychiatric medication use, psychiatric diagnoses, and the use of chronic opioids among these individuals.
Preview · Article · Feb 2006 · Arthritis & Rheumatology
[Show abstract][Hide abstract] ABSTRACT: In March 2004 the U.S. Food and Drug Administration (FDA) warned physicians and patients regarding increased risk of suicide with 10 newer antidepressant drugs. Available data leave considerable uncertainty regarding actual risk of suicide attempt and death by suicide during antidepressant treatment. The authors used population-based data to evaluate the risk of suicide death and serious suicide attempt in relation to initiation of antidepressant treatment.
Computerized health plan records were used to identify 65,103 patients with 82,285 episodes of antidepressant treatment between Jan. 1, 1992, and June 30, 2003. Death by suicide was identified by using state and national death certificate data. Serious suicide attempt (suicide attempt leading to hospitalization) was identified by using hospital discharge data.
In the 6 months after the index prescription of antidepressant treatment, 31 suicide deaths (40 per 100,000 treatment episodes) and 76 serious suicide attempts (93 per 100,000) were identified in the study group. The risk of suicide attempt was 314 per 100,000 in children and adolescents, compared to 78 per 100,000 in adults. The risk of death by suicide was not significantly higher in the month after starting medication than in subsequent months. The risk of suicide attempt was highest in the month before starting antidepressant treatment and declined progressively after starting medication. When the 10 newer antidepressants included in the FDA advisory were compared to older drugs, an increase in risk after starting treatment was seen only for the older drugs.
The risk of suicide during acute-phase antidepressant treatment is approximately one in 3,000 treatment episodes, and risk of serious suicide attempt is approximately one in 1,000. Available data do not indicate a significant increase in risk of suicide or serious suicide attempt after starting treatment with newer antidepressant drugs.
Preview · Article · Feb 2006 · American Journal of Psychiatry
[Show abstract][Hide abstract] ABSTRACT: There has been considerable debate about the potential relationship between the use of statin lipid-lowering drugs and fracture risk; several observational studies suggest a protective effect but no randomized controlled trials have confirmed such a benefit. Because statins are given preferentially to persons with hyperlipidemia, if lipid levels were associated with bone mineral density, this could explain the discrepancy between epidemiological observations and randomized controlled trials. The aim of this study was to examine the relationship between lipid levels and bone mineral density.
We included the 13592 participants in the National Health and Nutritional Examination Survey (NHANES) III who had bone mineral density and lipid levels measured; participants who reported the use of a lipid-lowering therapy were excluded. We examined the unadjusted bone mineral density across quintiles of total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). We then constructed multivariable models, including age, sex, body mass index, and other potential confounders.
In crude analyses, higher total cholesterol and LDL levels were associated with lower bone mineral densities (both P values for trend <.001), whereas higher HDL levels were associated with higher bone mineral densities (P value for trend <.001). However, in fully adjusted models, there was no significant relationship between total cholesterol, LDL, or HDL levels and bone mineral density (all P values for trend >.1).
These results do not support a relationship between lipid levels and bone mineral density.
No preview · Article · Jan 2006 · The American journal of medicine