[Show abstract][Hide abstract] ABSTRACT: Suicidal behavior has gained attention as an adverse outcome of prescription drug use. Hospitalizations for intentional self-harm, including suicide, can be identified in administrative claims databases using external cause of injury codes (E-codes). However, rates of E-code completeness in US government and commercial claims databases are low due to issues with hospital billing software.
To develop an algorithm to identify intentional self-harm hospitalizations using recorded injury and psychiatric diagnosis codes in the absence of E-code reporting.
We sampled hospitalizations with an injury diagnosis (ICD-9 800-995) from two databases with high rates of E-coding completeness: 1999-2001 British Columbia, Canada data and the 2004 US Nationwide Inpatient Sample. Our gold standard for intentional self-harm was a diagnosis of E950-E958. We constructed algorithms to identify these hospitalizations using information on type of injury and presence of specific psychiatric diagnoses.
The algorithm that identified intentional self-harm hospitalizations with high sensitivity and specificity was a diagnosis of poisoning, toxic effects, open wound to elbow, wrist, or forearm, or asphyxiation; plus a diagnosis of depression, mania, personality disorder, psychotic disorder, or adjustment reaction. This had a sensitivity of 63%, specificity of 99% and positive predictive value (PPV) of 86% in the Canadian database. Values in the US data were 74, 98, and 73%. PPV was highest (80%) in patients under 25 and lowest those over 65 (44%).
The proposed algorithm may be useful for researchers attempting to study intentional self-harm in claims databases with incomplete E-code reporting, especially among younger populations.
Pharmacoepidemiology and Drug Safety 10/2010; 19(12):1263-75. · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A US Food and Drug Administration advisory has warned that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in adolescents. This prompted a meta-analysis of trials in adults that found no overall increase in risk, but individual agents could not be studied.
To assess the risk of suicide and suicide attempts associated with individual antidepressant agents.
Cohort study of incident users of antidepressant agents.
Population-based health care utilization data of all residents of British Columbia, Canada, aged 18 years and older between January 1, 1997, and December 31, 2005.
British Columbia residents who had antidepressant therapy initiated and had a recorded diagnosis of depression.
Initiation of various antidepressant medications.
Combined suicide death or hospitalization due to self-harm.
In a population of 287,543 adults aged 18 years and older with antidepressant therapy initiated, we observed outcome rates ranging from 4.41/1000 person-years to 9.09/1000 person-years. Most events occurred in the first 6 months after treatment initiation. After extensive propensity score adjustment, we found no clinically meaningful variation in the risk of suicide and suicide attempt between antidepressant agents compared with fluoxetine hydrochloride initiation: citalopram hydrobromide, hazard ratio = 1.00 (95% confidence interval, 0.63-1.57); fluvoxamine maleate, hazard ratio = 0.98 (95% confidence interval, 0.63-1.51); paroxetine hydrochloride, hazard ratio = 1.02 (95% confidence interval, 0.77-1.35); and sertraline hydrochloride, hazard ratio = 0.75 (95% confidence interval, 0.53-1.05). Compared with selective serotonin reuptake inhibitors as a drug class, other classes including serotonin-norepinephrine reuptake inhibitors, tricyclic agents, and other newer and atypical agents had a similar risk. Restriction to patients with no antidepressant use in the past 3 years further reduced apparent differences between groups.
Our finding of equal event rates across antidepressant agents supports the US Food and Drug Administration's decision to treat all antidepressants alike in their advisory. Treatment decisions should be based on efficacy, and clinicians should be vigilant in monitoring after initiating therapy with any antidepressant agent.
Archives of general psychiatry 05/2010; 67(5):497-506. · 12.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents.
We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death.
Of 20,906 children who initiated antidepressant therapy, 16,774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9-30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54-1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46-2.43]), paroxetine (RR: 0.80 [95% CI: 0.47-1.37]), and sertraline (RR: 1.02 [95% CI: 0.56-1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43-2.00]).
Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants.
[Show abstract][Hide abstract] ABSTRACT: Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance.
To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+.
Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models.
Neither policy affected the rates of visits to physicians or psychiatrists for depression, hospitalizations with a depression diagnosis, or long-term care admissions.
The cost-sharing policies studied may have contained non-essential antidepressant use without substantially increasing mental health service utilization. However, it is possible that the policies had effects that we were unable to detect, such as increasing rates of visits to social workers or psychologists or forcing patients to reduce other spending. Further, the sequential implementation of the policy changes, makes it difficult to estimate the effect of a direct change from full coverage to a coinsurance/income-based deductible policy.
It may be possible to design policies to contain non-essential antidepressant use without substantially increasing other service utilization or adverse events. However, because undertreatment remains a serious problem among depressed elderly, well-designed prescription drug policies should be coupled with interventions to address under-treatment.
The Journal of Mental Health Policy and Economics 03/2010; 13(1):37-44. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 2003, more intense monitoring of patients initiating antidepressants was advised because of emerging concerns of suicidality. We sought to identify patterns of patient monitoring after antidepressant initiation in British Columbia before and after issuance of health advisories.
We conducted a cohort study of antidepressant initiators between 1999 and 2005 using healthcare utilization data of all British Columbia residents. For the periods before (1999-2001) and after (2004-2005), health advisories concerning suicidality associated with antidepressants, we assessed monitoring intensity by calculating weekly physician and psychotherapy visit rates since antidepressant initiation. We also estimated monitoring patterns as the proportion of individuals who received weekly in-person contact during the first 4 weeks of treatment, then biweekly visits for 4 weeks, and then a visit at 12 weeks, as a proxy for intensive monitoring.
Patterns of monitoring intensity were similar before and after the health advisories, but the level of intensity was lower after the advisory period. Overall, monitoring intensity peaked in the 4 weeks after antidepressant initiation. Weekly numbers of visits per subject during these 4 weeks were between 0.44 and 0.49 before the advisory and from 0.39 to 0.44 after the advisory. Among all initiators stratified by year of initiation, between 21% and 25% received intensive monitoring, and this proportion generally decreased on a yearly basis.
Monitoring intensity for patients with depression initiating antidepressants decreased after the period of emergence and greater awareness of the association between antidepressants and suicidality.
Journal of clinical psychopharmacology 12/2009; 29(6):590-4. · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: STAR*D (Sequenced Treatment Alternatives to Relieve Depression) continues to stimulate debate. The landmark trial demonstrated the feasibility of large-scale, community-based studies conducted without pharmaceutical company support. The results provided insight into nonresponse to initial treatment with selective serotonin reuptake inhibitors and alternatives for second- and third-line treatment options and suggested opportunities for personalized approaches to depression care. However, initial and one-year remission rates (28% and 70%, respectively) suggest that important goals for treatment of this disabling disease remain out of reach and that the bar for antidepressants has been set far too low.
[Show abstract][Hide abstract] ABSTRACT: This study sought to determine whether previously reported poor outcomes among patients of low socioeconomic status who have depression and anxiety could result from not receiving mental health treatment or from receiving minimally adequate treatment.
The study sample consisted of 1,772 participants in the National Comorbidity Survey Replication (NCS-R) who met criteria for a mood or anxiety disorder. Bivariate and multivariate logistic regression analyses were used to examine associations between education, income, and assets and receipt of treatment and quality of treatment (minimally adequate treatment) for mood and anxiety disorders in sectors with the capacity to deliver evidence-based treatments (the general medical and mental health specialty sectors). Multivariate analyses controlled for age, gender, race-ethnicity, marital status, health insurance, and urbanicity.
Age, gender, marital status, and race-ethnicity were strong and fairly consistent predictors of mental health services use, with some modest variations by sector. In contrast, in bivariate and multivariate analyses, education, income, and assets were minimally related to use of mental health care and to receipt of minimally adequate care in both general medical and mental health specialty sectors.
Socioeconomic status does not appear to play a major role in determining aspects of treatment for depression and anxiety disorders. Poor outcomes of depressed and anxious patients with low socioeconomic status may be due to differences in quality of care beyond the minimally adequate level assessed in this study or to factors unrelated to quality of care that could counteract effective treatments, such as the presence of ongoing chronic stress.
[Show abstract][Hide abstract] ABSTRACT: Although mental health treatment dropout is common, patterns and predictors of dropout are poorly understood. This study explored patterns and predictors of mental health treatment dropout in a nationally representative sample.
Data were from the National Comorbidity Survey Replication, a nationally representative household survey. Respondents who had received mental health treatment in the 12 months before the interview (N=1,664) were asked about dropout, which was defined as quitting treatment before the provider wanted them to stop. Cross-tabulation and discrete-time survival analyses were used to identify predictors.
Approximately one-fifth (22%) of patients quit treatment prematurely. The highest dropout rate was from treatment received in the general medical sector (32%), and the lowest was from treatment received by psychiatrists (15%). Dropout rates were intermediate from treatment in the human services sector (20%) and among patients seen by nonpsychiatrist mental health professionals (19%). Over 70% of all dropout occurred after the first or second visits. Mental health insurance was associated with low odds of dropout (odds ratio=.6, 95% confidence interval=.4-.9). Psychiatric comorbidity was associated with a trend toward dropout. Several patient characteristics differentially predicted dropout across treatment sectors and in early and later phases of treatment.
Roughly one-fifth of adults in mental health treatment dropped out before completing the recommended course of treatment. Dropout was most common in the general medical sector and varied by patient characteristics across treatment sectors. Interventions focused on high-risk patients and sectors that have higher dropout rates will likely be required to reduce the large proportion of patients who prematurely terminate treatment.
[Show abstract][Hide abstract] ABSTRACT: The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years (QALYs) were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, whereas likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year old with MDD, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93,520 per additional QALY compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost per QALY dropped below $50,000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios approximately 1.8-2.0. Tests for differential antidepressant response could thus become cost effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2009; 34(10):2227-36. · 8.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Making decisions about medical treatments based upon valid evidence is critical to improve health-care quality, outcomes, and value. Although such research commonly connotes the use of randomized controlled trials, experimental methods are not always feasible, and research using observational, quasi-experimental, and other nonexperimental methods may also be important. At the same time, nonexperimental methods are inherently susceptible to various types of bias and thus present special challenges in the search for valid and generalizable evidence. The study by Gardarsdottir et al. (Am J Epidemiol. 2009;170(3):280-285), on which this commentary is based, addresses a key potential source of bias -- mismeasurement of patients' duration of treatment -- in previous research on pharmacotherapy for depression. However, the authors' study is unlikely to address other potential sources of bias, which may make interpretation of their findings more difficult.
American journal of epidemiology 07/2009; 170(3):286-7; discussion 288. · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the lifetime and 12-month prevalence and associations of mental health treatment among Mexican adolescents with suicide-related outcomes (SROs; including ideation, plans, gestures and attempts).
A representative multistage probability household survey of 3005 adolescents aged 12 to 17 years residing in the Mexico City Metropolitan Area was carried out in 2005. Discrete-time survival analyses were used to assess the relationships between SROs and receiving treatment for emotional, alcohol, or drug problems.
The prevalence of lifetime service use among respondents with SROs was 35% for those with ideation only, 44% for those with ideation and plan, 49% for those with gesture and 50% for those with attempt; the prevalence of 12-month service use was 10%, 24%, 6% and 21%, respectively. Timing between onset of SRO and receiving treatment for emotional, alcohol, or drug problems showed that about 50% of adolescents will have contact with a service provider before developing any SRO. Healthcare professionals were the most likely to be consulted, followed by school-based programs.
This survey was limited to adolescents living in one of the largest metropolitan areas in the world and the analyses used data on retrospectively reported ages of onset that are subject to recall errors.
Most suicidal adolescents do not receive treatment, and many adolescents develop their suicidality in spite of prior contacts with service providers. Interventions to increase treatment, prevention, and monitoring are sorely needed for this vulnerable population.
Journal of Affective Disorders 06/2009; 120(1-3):32-9. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a pressing need for comparative effectiveness research to improve mental health treatments. Although U.S. mental health spending has increased dramatically, mainly because of the rapid adoption of newer psychotropic medications, fewer than a quarter of people with serious mental illnesses receive appropriate care. Because of a general lack of information on the relative effectiveness of different treatments, payers are uncertain about the value of current spending, which in turn may deter new investments to reduce unmet need. We use several recent comparative effectiveness trials to illustrate the potential value of such research for improving practice and policy.
Health Affairs 05/2009; 28(3):783-91. · 4.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The paper reviews recent findings from the WHO World Mental Health (WMH) surveys on the global burden of mental disorders.
The WMH surveys are representative community surveys in 28 countries throughout the world aimed at providing information to mental health policy makers about the prevalence, distribution, burden, and unmet need for treatment of common mental disorders.
The first 17 WMH surveys show that mental disorders are commonly occurring in all participating countries. The inter-quartile range (IQR: 25th-75th percentiles) of lifetime DSM-IV disorder prevalence estimates (combining anxiety, mood, externalizing, and substance use disorders) is 18.1-36.1%. The IQR of 12-month prevalence estimates is 9.8-19.1%. Prevalence estimates of 12-month Serious Mental Illness (SMI) are 4-6.8% in half the countries, 2.3-3.6% in one-fourth, and 0.8-1.9% in one-fourth. Many mental disorders begin in childhood-adolescence and have significant adverse effects on subsequent role transitions in the WMH data. Adult mental disorders are found to be associated with such high role impairment in the WMH data that available clinical interventions could have positive cost-effectiveness ratios.
Mental disorders are commonly occurring and often seriously impairing in many countries throughout the world. Expansion of treatment could be cost-effective from both employer and societal perspectives.
Epidemiologia e psichiatria sociale 03/2009; 18(1):23-33. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonrandomised studies on the causal effects of psychotropic medications may be biased by patient characteristics that are not fully adjusted.
Studies using linked claims databases found that typical antipsychotic medications were associated with increased short-term mortality compared with atypical antipsychotics. It has been suggested that such results may be due to residual confounding by factors that cannot be measured in claims databases. Using detailed survey data we identified the direction and magnitude of such residual confounding.
Cross-sectional survey data.
17 776 participants aged > or =65 years from the Medicare Current Beneficiary Survey (MCBS).
To determine the association between typical antipsychotic use and potential confounding factors we assessed five factors not measured in Medicare claims data but in the MCBS, i.e. body mass index, smoking, activities of daily living (ADL) score, cognitive impairment and Rosow-Breslau physical impairment scale. We estimated adjusted associations between these factors and antipsychotic use. Combined with literature estimates of the independent effect of confounders on death, we computed the extent of residual confounding caused by a failure to adjust for these factors.
Comparing typical antipsychotic users with atypical antipsychotic users, we found that not adjusting for impairments in the ADL score led to an underestimation of the association with death (-13%), as did a failure to adjust for cognitive impairment (-7%). The combination of all five unmeasured confounders resulted in a net confounding of -5% (range -19% to +2%). After correction, the reported association between typical antipsychotic use and death compared with atypical antipsychotic use was slightly increased from a relative risk (RR) of 1.37 to 1.44 (95% CI 1.33, 1.56). Comparing any antipsychotic use with non-users would result in overestimations of >50% if cognitive impairment remained unadjusted.
Claims data studies tend to underestimate the association of typical antipsychotics with death compared with atypical antipsychotics because of residual confounding by measures of frailty. Studies comparing antipsychotic use with non-users may substantially overestimate harmful effects of antipsychotics.
[Show abstract][Hide abstract] ABSTRACT: Translational research is urgently needed to turn basic scientific discoveries into widespread health gains and nowhere are these needs greater than in conditions such as schizophrenia and other psychotic disorders. In this article, we discuss one type of translational research--called T1--which is needed to take advantage of developments in the basic neurosciences and translate them into more efficacious diagnostic, preventive, and therapeutic interventions. However, ensuring that interventions from T1 research actually benefit patients will require a second form of translational research--called T2--to turn innovations into everyday clinical practice and health decision-making. Recent examples of T1 and T2 research in schizophrenia and other psychotic disorders as well as strategies for better linking T1 and T2 research agendas are covered.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2008; 34(1):204-12. · 8.68 Impact Factor