Article

Changes in Physician Antipsychotic Prescribing Preferences, 2002-2007

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Abstract

Objective: Physician antipsychotic prescribing behavior may be influenced by comparative effectiveness evidence, regulatory warnings, and formulary and other restrictions on these drugs. This study measured changes in the degree to which physicians are able to customize treatment choices and changes in physician preferences for specific agents after these events. Methods: The study used 2002-2007 prescribing data from the IMS Health Xponent database and data on physician characteristics from the American Medical Association for a longitudinal cohort of 7,399 physicians. Descriptive and multivariable regression analyses were conducted of the concentration of prescribing (physician-level Herfindahl index) and preferences for and likelihood of prescribing two first-generation antipsychotics and six second-generation antipsychotics. Analyses adjusted for prescribing volume, specialty, demographic characteristics, practice setting, and education. Results: Antipsychotic prescribing was highly concentrated at the physician level, with a mean unadjusted Herfindahl index of .33 in 2002 and .29 in 2007. Psychiatrists reduced the concentration of their prescribing more over time than did other physicians. High-volume psychiatrists had a Herfindahl index that was half that of low-volume physicians in other specialties (.18 versus .36), a difference that remained significant (p<.001) after adjustment for physician characteristics. The share of physicians preferring olanzapine dropped from 29.9% in 2002 to 10.3% in 2007 (p<.001) while the share favoring quetiapine increased from 9.4% to 44.5% (p<.001). Few physicians (<5%) preferred a first-generation antipsychotic in 2002 or 2007. Conclusions: Preferences for specific antipsychotics changed dramatically during this period. Although physician prescribing remained heavily concentrated, the concentration decreased over time, particularly among psychiatrists.

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... Consequently, the treatment of schizophrenia and bipolar disorders should be tailored to individual patients, which is typically the case in developed countries 27,28 . This has resulted in changes in prescribing patterns as different antipsychotic medicines become available 29 , with the World Health Organization (WHO) EML recommending chlorpromazine, fluphenazine, haloperidol, with potentially risperidone, depending on costs 9 . Anticholinergic medicines have also been used to alleviate neuroleptic-induced extrapyramidal side-effects 30 . ...
... Utilization and expenditure data for the antipsychotics (N05A group apart from Lithium -N05AN 73 ) from 2010-2015 were extracted from Intercontinental Marketing Services (IMSnow QuintilesIMS TM ) data to provide insight into current utilization and expenditure patterns. IMS collects data of drug statistic sales from a representative sample of pharmacies in Pakistan to provide representational data for Pakistan, with IMS data internationally recognized for comparing drug utilization statistics across countries 29,74 . IMS data was sourced via the Drugs Regulatory Authority in Pakistan (DRAP) for academic purposes. ...
... If anything, there was a significant decrease in the prescribing of aripiprazole in some years, although marginally increased prescribing in recent years, albeit from a limited base (Table 2). Overall, differences in prescribing habits within and between countries may be due to physician preferences, different patient responses to available treatments, availability of generic vs brand choices, and costs 29,35,82 . For typical antipsychotics, haloperidol was one of the commonest used medicines in both groups (Tables 2 and 6), which is similar to Canadian and Australian studies 84,87 , potentially enhanced by its inclusion in the WHO essential medicines list 9 . ...
Article
Introduction and objectives: There is a paucity of antipsychotic prescribing and utilization data in Pakistan that needs addressing, especially with issues of availability, affordability, gender differences, and domestic violence, to develop pertinent strategies. The objective of this study was to address these issues by describing current antipsychotic utilization patterns in Pakistan among adult patients attending tertiary care hospitals and private practitioners. Methods: A three staged approach was used including 1/assessment of total antipsychotic utilization, expenditure and costs per unit between 2010 and 2015, 2/an in-depth retrospective study of prescribing patterns including co-morbidities among representative hospital patients in Pakistan, and 3/assessment of the quality of prescribing against WHO targets. Results: Total use of antipsychotics increased 4.3-fold and the cost/unit increased by 13.2% during the study period. Risperidone and olanzapine were the most prescribed antipsychotics with more limited use of other typical and atypical antipsychotics. The number of medicines per encounter was 4.56. Prescription using generic instead of brand names was 21.4%. Seven percent was prescribed more than one antipsychotic concurrently. Conclusion: There has been an appreciable increase in anti-psychotic utilization in recent years in Pakistan especially atypical antipsychotics, with little polypharmacy. Ongoing utilization of typical antipsychotics may be due to comorbidities such as diabetes and cardiovascular disease. Issues of international non-proprietary name prescribing need investigating along with the high number of medicines per encounter and gender inequality.
... More broadly, the psychiatric literature has discussed heterogeneity in terms of meta-analysis, the combinatorial enumerations of symptom profiles (i.e., the "number of ways" disorder X can present) [3][4][5][6][7] , cluster analyses 8,9 , dimensional models 10 , concentration or inequality measures 11,12 , time-series complexity 13 , and recently in terms of "normative models" 14,15 . Unfortunately, we have neither a unified operational definition nor clear measure for this concept 16 . ...
... which gives the probability that two samples from our system will belong to the same category. Psychiatric researchers have used this to measure the homogeneity of physicians' and health systems' prescription repertoires 11,12 . ...
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Article
Heterogeneity is an important concept in psychiatric research and science more broadly. It negatively impacts effect size estimates under case–control paradigms, and it exposes important flaws in our existing categorical nosology. Yet, our field has no precise definition of heterogeneity proper. We tend to quantify heterogeneity by measuring associated correlates such as entropy or variance: practices which are akin to accepting the radius of a sphere as a measure of its volume. Under a definition of heterogeneity as the degree to which a system deviates from perfect conformity, this paper argues that its proper measure roughly corresponds to the size of a system’s event/sample space, and has units known as numbers equivalent. We arrive at this conclusion through focused review of more than 100 years of (re)discoveries of indices by ecologists, economists, statistical physicists, and others. In parallel, we review psychiatric approaches for quantifying heterogeneity, including but not limited to studies of symptom heterogeneity, microbiome biodiversity, cluster-counting, and time-series analyses. We argue that using numbers equivalent heterogeneity measures could improve the interpretability and synthesis of psychiatric research on heterogeneity. However, significant limitations must be overcome for these measures—largely developed for economic and ecological research—to be useful in modern translational psychiatric science.
... Multimodality refers to different categories, strata, or distributions being represented within a given set or sample. In the psychiatric literature, the multimodality view of heterogeneity is implied in studies of symptom combination diversity, 14 microbial biodiversity 15 and diversity of prescribing habits, 16,17 to name a few. However, it is the large number of clustering and latent class analyses that signify our field's tendency to view heterogeneity as reflective of multimodality in our data. ...
... 22 Both the Shannon and Gini indices, or variations thereof, have been used to quantify diversity in psychi atric symptom presentations 14 and gut microbial flora 15 in psychiatric disorders as well as heterogeneity of psychotropic prescribing patterns. 16,17 However, these indices can be difficult to interpret and synthesize because they do not measure heterogeneity directly, but rather common secondary properties of heterogeneous sets. 23 Perhaps the most common approach for characterizing heterogeneity in the psychiatric literature has been to count the number of latent clusters or factors inferred from data under some unsupervised learning model. ...
... Second-generation antipsychotics (SGAs) are primarily indicated for the treatment of schizophrenic disorders, and some SGA such as quetiapine, risperidone, aripiprazole, and lurasidone also have labeled indications for other psychiatric disorders including bipolar diseases. A pronounced increase in the use of antipsychotics has been observed over the past 20 years, which is mostly attributable to the increased prescription of SGA since their introduction in the mid 1990s (Verdoux et al., 2010;Donohue et al., 2014). Off-label use has also been reported to be very common for SGA in clinical practicefor example, for the treatment of dementia and symptoms of anxiety, sleep, and neurotic disorders (Linden and Thiels, 2001;McKean and Monasterio, 2012). ...
... Quetiapine and olanzapine accounted for the majority of SGA use, and both are well known to cause metabolic disorders and QT prolongation. The predominant use of quetiapine is also in line with previous reports (Greil et al., 2012;Donohue et al., 2014), and quetiapine is subject to drug interactions with inducers and inhibitors of CYP3A4 drug-metabolizing enzymes. Inducers and inhibitors of CYP450 enzymes are used frequently in tertiary care hospitals including for example several antiepileptic, antifungal, and antibiotic drugs. ...
Article
We carried out an observational study that analyzed population characteristics, metabolic profiles, potentially interacting pharmacotherapy, and related adverse events in second-generation antipsychotics (SGAs) users of a tertiary care hospital. Within our pharmacoepidemiological database derived from electronic medical records of 82 358 hospitalizations, we identified 1136 hospitalizations contributing 9165 patient-days with exposure to SGA. Blood pressure, blood glucose, lipids, and BMI had been documented in 97.7, 75.7, 24.6, and 77.4% of hospitalizations, respectively. Among these, the prevalence of hypertension, hyperglycemia, dyslipidemia, and BMI 30 kg/m or more was 36.9, 22.6, 61.1, and 23.1%, respectively. A total of 63.4, 70.8, and 37.1% of SGA users with hyperglycemia, dyslipidemia, and hypertension, respectively, received no pharmacotherapy for these conditions. We identified 614 patient-days with SGA plus formally contraindicated comedication and another 1066 patient-days with other high-risk combinations for QTc prolongation. Among those there was one case with associated neutropenia and four cases with abnormal QTc interval. However, specific monitoring for such adverse events was not documented in 45.5% of hospitalizations with contraindicated and 89.8% with high-risk QTc-prolonging combinations. Our study identified targets for improved monitoring and management in SGA users. These may be implemented as automated alerts into electronic prescribing systems and thereby efficiently support safer pharmacotherapy in clinical practice.
... 11,12 Due to their metabolic adverse effects, which can drive patients into partial and/or total nonadherence to treatment, efforts to reduce the use of AAP have been made. [13][14][15] Nevertheless, they remain the reference medications in the treatment of schizophrenia. 16 Given the wide use of AAP, a deeper understanding of the mechanisms leading to AIWG and/or metabolic impairments is essential. ...
Article
Background: Atypical antipsychotics can induce metabolic side effects, but whether they are dose-dependent remains unclear. Objective: To assess the effect of risperidone and/or paliperidone dosing on weight gain and blood lipids, glucose, and blood pressure alterations. Methods: Data for 438 patients taking risperidone and/or its metabolite (paliperidone) for up to 1 year were obtained between 2007 and 2018 from a longitudinal study monitoring metabolic parameters. Results: For each milligram increase in dose, we observed a weight increase of 0.16% at 1 month of treatment (P = .002) and increases of 0.29%, 0.21%, and 0.25% at 3, 6, and 12 months of treatment, respectively (P < .001 for each). Moreover, dose increases of 1 mg raised the risk of a ≥ 5% weight gain after 1 month (OR = 1.18; P = .012), a strong predictor of important weight gain in the long term. When we split the cohort into age categories, the dose had an effect on weight change after 3 months of treatment (up to 1.63%, P = .008) among adolescents (age ≤ 17 years), at 3 (0.13%, P = .013) and 12 (0.13%, P = .036) months among adults (age > 17 and < 65 years), and at each timepoint (up to 1.58%, P < .001) among older patients (age ≥ 65 years). In the whole cohort, for each additional milligram we observed a 0.05 mmol/L increase in total cholesterol (P = .018) and a 0.04 mmol/L increase in LDL cholesterol (P = .011) after 1 year. Conclusions: Although of small amplitude, these results show an effect of daily risperidone dose on weight gain and blood cholesterol levels. Particular attention should be given to the decision of increasing the drug dose, and minimum effective dosages should be preferred.
... However, GPs in the UK are responsible for continuing treatments initiated in specialist settings and these data are more likely to accurately to represent overall national trends than if it were to be obtained from secondary care. A previous small study among London psychiatrists highlighted the disproportionate prescribing of SGAs over FGAs over time [41] a pattern that is following suit internationally [42]. ...
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Article
Background Increasing rates of antipsychotic prescribing have been reported previously, particularly for second-generation antipsychotics (SGAs), which are generally better tolerated than the older first-generation antipsychotics (FGAs). Prescribers, however, may exert bias, favouring prescriptions of novel drugs for patients of higher socioeconomic status (SES). We aimed to examine time trends in: (1) prescriptions of oral FGAs vs. SGAs and (2) associations between antipsychotic prescriptions and neighbourhood-level SES in England between 2011 and 2016. Methods We used publicly available data for prescriptions made in primary care and linked general practices’ postcodes with the Index of Multiple Deprivation (IMD) as a measure for neighbourhood-level SES. Absolute numbers of antipsychotic prescriptions were calculated. Linear regression analysis was used to examine the association of SGA vs. FGA prescription pattern with time and with SES. Results A total of 27,486,000 oral antipsychotics were prescribed during the study period, mostly SGAs (n = 21,700,000; 78.9%). There was a significant increase in the ratio of SGA/FGA prescriptions over time (β = 0.376, 95% CI 0.277–0.464, P < 0.001). Individual FGAs were increasingly prescribed in areas of lower SES and the converse for SGAs except amisulpride. During the study period, a significantly larger proportion of total SGA prescriptions relative to total FGAs were made in areas of higher SES (β = 0.182, 95% CI 0.117–0.249, P < 0.001). Conclusion Prescriptions of antipsychotics continue to rise overall, with SGAs taking preference especially in areas of higher SES. The pattern of antipsychotic prescription favouring people in areas of lower social deprivation carries implications on inequalities even among sub-groups of people with mental disorders.
... Third, we obtained physician-level prescribing data from QuintilesIMS Xponent™ which directly captures > 70% of all US prescriptions filled in retail pharmacies, including all payers (Medicare, Medicaid fee-for-service, commercial insurance, cash, and uninsured). Xponent™ utilizes a patented proprietary projection method to represent 100% of prescriptions filled in these outlets and has been widely used by researchers to examine medication use patterns [9,[16][17][18][19][20]. Our Xponent™ data includes all physician prescribers practicing in PA during January 2007-December 2011. ...
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Article
Background: In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania. Methods: We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model regression, adjusting for patient socio-demographic/clinical characteristics, was used to examine the association between physician adoption of sitagliptin and AD drug spending. Results: Physician adoption of sitagliptin varied from 44 to 99% across the state's 67 counties. Average per capita AD spending was $1340 (SD $1764) in Medicare and $1291 (SD $1881) in Medicaid. A 10% increase in the share of physicians adopting sitagliptin in a county was associated with a 3.5% (95% CI: 2.0-4.9) and 5.3% (95% CI: 0.3-10.3) increase in drug spending for the Medicare and Medicaid populations, respectively. Conclusions: In a medication market with many choices, county-level adoption of sitagliptin was positively associated with AD spending in Medicare and Medicaid, two programs with different approaches to formulary management.
... The baseline predictors included the log of total PACE prescriptions, log of total PACE patients, mean PACE claims per patient, percentage of patients with diabetes, mean patient age, percentage of PACE prescriptions that were for patients in the traditional PACE (lower-income) program versus the PACE Needs Enhancement Tier (higher-income) program, percentage of prescriptions that were for patients in long-term care, prescriber type (medical doctor or doctor of osteopathy vs certified registered nurse practitioner or physician assistant), length of time licensed in Pennsylvania (≥10 years vs <10 years), prescriber sex, and the Herfindahl concentration index of the therapeutic classes that were prescribed (a measure of the prescribed drug class diversity that reflects the relative breadth of the prescriber's clinical focus). 28 The propensity logistic regression coefficients, which are a weighted composite of variables that maximally differentiate the detailed from nondetailed prescribers within the intervention counties, were then used to score the data for all nondetailed prescribers who practiced in the Pennsylvania counties where the intervention was not offered. Finally, a 1:1 optimal matching, with a maximum radius using a SAS macro, 29 was used to match each detailed prescriber to the nonintervention county prescriber with the closest matching logit of the propensity score, provided that the comparison prescriber was located in a county with a similar level of urbanization and also met the same basic activity requirements outlined earlier for the intervention group. ...
Article
Background: Publicly funded prescription drug programs, such as state pharmacy assistance programs, provide critical benefits for the care of individuals, but they are frequently limited in their resources to optimize patient outcomes. The application of quality metrics to prescription drug claims may help to determine whether prescribers' adherence to national standards can be augmented through academic detailing. Objective: To evaluate changes in diabetes drug prescribing patterns after an academic detailing educational intervention in 2013 and 2014 for prescribers in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) program. Methods: We used a retrospective, quasiexperimental study design that applied interrupted time series and segmented regression analysis, and examined PACE pharmacy claims data for 1 year before and 1 year after the academic detailing intervention. Four diabetes prescribing metrics were evaluated at monthly intervals for a sample of 574 prescribers who received academic detailing and for a propensity score-matched comparison sample of 574 prescribers who did not receive the intervention. Results: The prescribers who received academic detailing did not differ significantly after the intervention from the providers who did not receive the intervention in their prescribing trends for the 4 diabetes metrics. The observed time series patterns suggest that diabetes-related ceiling effects were likely, with relatively small room for improvement at the group level during the study period. Conclusion: The results of this study did not demonstrate group differences in prescribing trends that were attributable to the intervention. However, many prescribers in the detailed group had been exposed to similar educational outreach by PACE before 2013, which limits the interpretation of this finding. In addition, the diabetes quality metrics had been the standard of care during the preceding decade, with a broad dissemination of the treatment guidelines to the provider community. These results are consistent with a ceiling effect in the measured metrics, suggesting that most prescribers in both groups were largely following core diabetes guidelines before and after the intervention.
... [7][8][9][10][11][12] It is therefore critical to understand antipsychotic drug risks, particularly those associated with some frequently used second-generation antipsychotics (SGAs). Several developments, including a U.S. Food and Drug Administration class warning on the metabolic risks of SGAs and the introduction of metabolically safer drugs, have had some impact on prescribing patterns in the U.S. 13,14 However, SGAs with established or uncertain metabolic effects remain popular, even among patients with excessive weight and cardiometabolic disorders. ...
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Article
People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard 'as-randomized' analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of specific second-generation antipsychotics on weight gain, defined as at least a 7% increase in weight from randomization, using a Bayesian hierarchical model network meta-analysis with individual patient level data. Our data consisted of 14 randomized clinical trials contributing 5923 subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine (n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n = 1368). The median time from randomization to dropout or trial completion was 6 weeks (range: 0-60 weeks). The unadjusted probability of weight gain in the placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was estimated with considerable uncertainty but no different from paliperidone (odds ratio = 1.3 [1.2, 1.5]).
... Regarding the above-mentioned growth in atypical antipsychotic use, several antipsychotic substances have specifically contributed to this trend. This is particularly the case with quetiapine, which has become the mostprescribed antipsychotic in several countries in recent years (Table 3) (Carton et al., 2015;Donohue et al., 2014;Duncan et al., 2016;Morrens et al., 2015). ...
Article
The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0–19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20–64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.
... In Spain, olanzapine and risperidone were reported [11]. However, quetiapine is the most prescribed antipsychotic for off-label use in general mental disorders by psychiatrists in New Zealand and physicians in the US [47,48]. Although quetiapine was the most commonly prescribed antipsychotic by psychiatrists for schizophrenia in our study, almost all of it was used in the polypharmacy group. ...
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Article
Background: This study investigates the antipsychotic use patterns of patients with schizophrenia and its correlations in their daily drug use patterns. Methods: Patients with schizophrenia who have regular records at two different community counselling centres (CCS) were included in the study. Information about their medications and sociodemographic data was recorded through face-to-face interviews and supporting information about their drug use patterns was obtained from their relatives/caregivers/nurse. The Clinical Global Impression Scale (severity of illness) and the General Assessment of Functionality scales were also administered. Results: Patients with schizophrenia used 2.0 ± 0.81 antipsychotics daily and 3.52 ± 2.55 pills (1–18). Seventy-one percent of the patients used two or more kinds of psychotropic drugs. The most frequently used antipsychotics were quetiapine, a second generation antipsychotic, and haloperidol, a typical antipsychotic. Clinical severity, regular visits to a CCS and use of depot antipsychotics were independent predictors for polypharmacy. Conclusion: The rate of polypharmacy use is high in Turkey. There are multiple risk factors related with polipharmacy. New studies should focus risk factors for preventing polypharmacy.
... For example, while temazepam and midazolam were the most frequently prescribed drugs, they might not have been used as often in other studies performed at another time or in another country [33,34]. The personal or guideline-based treatment preferences of physicians may change over time, and new drugs may become available on the market [35,36]. Given the differential prescription rates of individual drugs, a fair comparison between the studies was difficult. ...
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Article
Background Older people are more susceptible to falls than younger people. Therefore, as the Dutch population ages, the total number of falls and costs associated with them will rise. The use of psychotropic drugs is associated with an increased risk of falling. To create tailored fall-prevention programmes, information on the magnitude of the association between fall incidents and specific psychotropic drugs or drug classes is needed. Objective The goal of this study was to delineate the associations between fall incidents and specific psychotropic drugs or drug classes. Methods In this retrospective cohort study, electronic patient records, medication records and fall incident reports were collected for 1415 residents receiving somatic or psychogeriatric care in 22 nursing homes in the eastern part of the Netherlands from May 2012 until March 2015. Using a Cox proportional hazards model, we analysed the magnitude of the association between psychotropic drugs and the risk of falling for users and non-users of the psychotropic drugs or drug classes. ResultsAntipsychotics (adjusted hazard ratio [aHR] 1.49; 95% confidence interval [CI] 1.12–2.00) and hypnotics and sedatives (aHR 1.51; 95% CI 1.13–2.02) increase the risk of falling. There was no difference between the risk incurred by typical and atypical antipsychotics. However, within these groups, there were differences between the most commonly prescribed drugs: haloperidol and quetiapine were seen to have an association with falls, whereas pipamperone and risperidone were not. Conclusions The results suggest falls may be associated with individual drugs rather than drug classes. Within the drug classes, clear differences are evident between individual drugs. Future fall-prevention programmes should highlight the differential risks involved with the use of specific psychotropic drugs, and doctors should take the fall risk into account when choosing specific drugs.
... Xponent™ directly captures >70% of all US prescriptions filled in retail pharmacies and utilizes a patented proprietary projection method to represent 100% of prescriptions filled in these outlets. 9,15,[20][21][22] We obtained monthly physician-level data on all oral anticoagulant prescriptions dispensed in Pennsylvania between October 1, 2009 and December 31, 2011. Xponent™ contains limited patient-level information relevant to the prescriptions including the source of payment (Medicare, Medicaid fee-for-service (FFS), commercial insurance, cash or uninsured), and patient age, with no patient identifiers. ...
Article
Background: Variation in physician adoption of new medications is poorly understood. Traditional approaches (eg, measuring time to first prescription) may mask substantial heterogeneity in technology adoption. Objective: Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant. Methods: A retrospective cohort study using prescribing data from IMS Xponent™ on all Pennsylvania physicians regularly prescribing anticoagulants (n=3911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription and group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions. Outcomes: Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran. Results: We identified 5 distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in ≤3 mo with 45% of prescriptions) and 13.4% were rapid and moderate adopters (≤3 mo with 20% share). Two groups accounting for 21.6% and 16.1% of physicians, respectively, were slower to adopt (6-10 mo post-introduction) and dabigatran accounted for <10% share. Nearly half (45.2%) of anticoagulant prescribers did not adopt dabigatran. Cardiologists were much more likely than primary care physicians to rapidly adopt [odds ratio (OR)=12.2; 95% confidence interval (CI), 9.27-16.1] as were younger prescribers (age 36-45 y: OR=1.49, 95% CI, 1.13-1.95; age 46-55: OR=1.34, 95% CI, 1.07-1.69 vs. >55 y). Conclusions: Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment.
... There are a number of potential explanations for this unexpected finding. First, policy implementation by AMCs may influence prescribing less than other factors including comparative effectiveness research, regulatory warnings, media attention to fraudulent marketing, patient preferences and characteristics, 32 physician training and prescribing volume, 33 professional guidelines, 34 and FDA advisories. 35 We chose a difference-in-differences analysis approach to try to account for these secular trends. ...
Article
Academic medical centers (AMCs) have increasingly adopted conflict of interest policies governing physician-industry relationships; it is unclear how policies impact prescribing. To determine whether 9 American Association of Medical Colleges (AAMC)-recommended policies influence psychiatrists' antipsychotic prescribing and compare prescribing between academic and nonacademic psychiatrists. We measured number of prescriptions for 10 heavily promoted and 9 newly introduced/reformulated antipsychotics between 2008 and 2011 among 2464 academic psychiatrists at 101 AMCs and 11,201 nonacademic psychiatrists. We measured AMC compliance with 9 AAMC recommendations. Difference-in-difference analyses compared changes in antipsychotic prescribing between 2008 and 2011 among psychiatrists in AMCs compliant with ≥7/9 recommendations, those whose institutions had lesser compliance, and nonacademic psychiatrists. Ten centers were AAMC compliant in 2008, 30 attained compliance by 2011, and 61 were never compliant. Share of prescriptions for heavily promoted antipsychotics was stable and comparable between academic and nonacademic psychiatrists (63.0%-65.8% in 2008 and 62.7%-64.4% in 2011). Psychiatrists in AAMC-compliant centers were slightly less likely to prescribe these antipsychotics compared with those in never-compliant centers (relative odds ratio, 0.95; 95% CI, 0.94-0.97; P<0.0001). Share of prescriptions for new/reformulated antipsychotics grew from 5.3% in 2008 to 11.1% in 2011. Psychiatrists in AAMC-compliant centers actually increased prescribing of new/reformulated antipsychotics relative to those in never-compliant centers (relative odds ratio, 1.39; 95% CI, 1.35-1.44; P<0.0001), a relative increase of 1.1% in probability. Psychiatrists exposed to strict conflict of interest policies prescribed heavily promoted antipsychotics at rates similar to academic psychiatrists and nonacademic psychiatrists exposed to less strict or no policies.
... While multiple antipsychotic prescribing was reduced, there was a shift to prescribing multiple SGAs that increased from 6.8% of all antipsychotics prescribed in 2008 to 9.2% in 2012. This pattern mirrors a general shift from FGA to SGA prescribing (Donohue et al. 2014). ...
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Objectives. To examine the impact of a change in local prescribing policy on the adherence to evidence-based prescribing guidelines for antipsychotic medication in a general adult psychiatric hospital. Methods. All adult in-patients had their clinical record and medication sheet reviewed. Antipsychotic prescribed, dose prescribed and documented indications for prescribing were recorded. This was done before and after the implementation of the change in hospital antipsychotic prescribing policy. Results. There were no significant differences in age, sex, Mental Health Act status, psychiatric diagnosis or documented indications for prescribing multiple or high dose antipsychotics between the two groups. There was an increase in the preferential prescribing of multiple second-generation antipsychotics (p = 0.01) in the context of a significant reduction in the prescribing of multiple antipsychotics overall (p = 0.02). There were no significant reductions in prescribing of mixed generations of antipsychotics (p = 0.12), high dose antipsychotics (p = 1.00) or as required (PRN) antipsychotics (p = 0.74). Conclusions. Changes in local prescribing policy can improve adherence to quality prescribing guidelines and cause clinically significant improvements in patterns of prescribing in a general adult psychiatric hospital.
Article
Background The trade-offs between innovation and pharmaceutical access are central to the policy debate on drug pricing. High prices may limit access, result in medication underuse, and negatively affect outcomes. Generic drugs make treatments more affordable. Prior research measured access as utilization without a defined population that should receive certain drugs, it is unknown whether generic entry reduces underuse and thus improves access. Objectives To measure changes in access (use, timeliness) with the introduction of three generic aromatase inhibitors (AIs, oral breast cancer drugs) between June 2010 and June 2011. Methods This population-based study included 93,650 older (65+) women diagnosed with hormone receptor-positive breast cancer between 2007 and 2013 in the Surveillance, Epidemiology and End Results-Medicare linked database. We examined changes in access with generic entry for initiation of any adjuvant hormonal therapy drug (AIs or tamoxifen) within one year of diagnosis, time from diagnosis to initiation, and choice of initial therapy. Results Among 93,650 newly diagnosed breast cancer cases, 67,372 initiated one of the four drugs. With generic entry, initiation rates increased from 69.5% to 74.3%, but non-initiation remained high (up to 25.7%). After controlling for demographics, clinical factors, and insurance coverage, the probability of initiation increased by 4.6 percentage points (P<0.001, 95%CI: [4.1,5.2]) after generic entry. With generic entry, estimated time to initiation decreased by 0.3 months (P<0.001, 95%CI: [0.2,0.3]) from 4.1 months, and the probability of choosing AIs over tamoxifen increased 5.9 percentage points (P<0.001, 95%CI: [5.3,6.5]). Patterns did not substantially differ by level of cost-sharing. Conclusions Generic entry of AIs was associated with increased probability of receiving recommended treatments, timeliness of treatment, and the probability of receiving clinically preferred treatments. Price changes with generic entry only partially explained these improvements. High non-initiation rates after generic entry suggest prices are not the sole determinant of access.
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Objective: Second-generation antipsychotics vary in their propensity to cause serious cardiometabolic side effects. In addition, use of two or more antipsychotics (polypharmacy) may lead to additive side effects and has not been shown to be consistently more effective than monotherapy. This study examined the use of academic detailing with audit and feedback to improve antipsychotic prescribing practices, including antipsychotic polypharmacy and utilization of medication with high or low risk of cardiometabolic side effects ("high risk" or "low risk," respectively). Methods: Four intervention sessions were provided over two years to psychiatric care providers at community mental health centers. Segmented regression within the general estimating equation model framework used Medicaid pharmacy claims to examine prescribing patterns before and after the intervention among all beneficiaries (67,721 person-months) over a five-year period. Results: After the intervention, 10.9% of beneficiaries with antipsychotic claims were on polypharmacy, compared with 13.1% before the invention. Use of high-risk and low-risk antipsychotics did not change. The final adjusted polypharmacy model showed that antipsychotic polypharmacy decreased among young adults and adults ages 40 or older compared with beneficiaries ages 30-39 (β=-.02, p=.04, and β=-.02, p=.007, respectively). The raw proportion of beneficiaries on high- and low-risk agents did not change, although final adjusted models demonstrated changes in use of high- and low-risk agents by diagnosis and risk group. Conclusions: Polypharmacy decreased among young and older adults after academic detailing with audit and feedback. Although further research is needed, this low-intensity intervention may help mental health systems reduce antipsychotic polypharmacy.
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Background: Although the evidence and the guidelines clearly state that with the exception of clozapine, there is no difference in efficacy between first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), this is not reflected in today’s practice, which is dominated by SGAs. Objective: We sought to identify the training needs and barriers to prescribing antipsychotics for the next generation of psychiatrists. Methods: We surveyed Canadian psychiatry residents on their attitudes, experiences, and knowledge regarding FGAs, SGAs, as well as long-acting injectable antipsychotics (LAIs), and clozapine. Results: Nearly two-thirds of residents were aware that FGAs and SGAs had similar efficacy. Roughly the proportion also perceived FGAs to have more or 'stronger' side-effects than SGAs. A lack of training experience was noted as the second leading concern for prescribing FGAs (23%) after concerns regarding extrapyramidal side effects (35%). Conclusion: Our survey has highlighted some worrying gaps in training. A focus on improving resident education and training to increase their experience with initiating all modalities of antipsychotic pharmacotherapy will reduce the risk that these tools are not lost to the future generations of psychiatrists
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Background: Atypical antipsychotics are used as monotherapy or as augmentation therapy for management of late-life depression. However, little is known about utilization pattern of atypical antipsychotics in depression in the elderly. Objective: The objective of this study was to examine the prescribing practices and predictors of atypical antipsychotics and augmentation therapy in elderly outpatient visits with depression. Methods: This retrospective cross-sectional study used the National Ambulatory Medical Care Survey (NAMCS) and outpatient department component of the National Hospital Ambulatory Medical Care Survey (NHAMCS) data from 2010 and 2011. The study included elderly (age ≥ 65years) outpatient visits with depression. Descriptive weighted analysis was performed to determine the prescribing practices of atypical antipsychotics and multivariable logistic regression analyses were performed to determine the factors associated with the prescription of atypical antipsychotics and augmentation therapy in outpatient visits. Results: According to the national surveys, there were about 22 million outpatent visits for depression during the study period; atypical antipsychotics were prescribed in 3.53% (95% CI, 2.02-5.04) of the visits. Among depression patients who were using antidepressants, 4.86% (95% CI, 3.07-6.04) used as an augmentation therapy. Multivariable regression analysis revealed that Hispanics (odds ratio [OR] = 0.33; 95% CI, 0.12-0.90) were associated with decreased likelihood of antipsychotic prescription, whereas personality disorder and obsessive compulsive disorder (OR = 10.23; 95% CI, 2.80-37.40) were associated with increased likelihood of prescribing antipsychotics. For augmentation therapy, Hispanics (OR = 0.06; 95% CI, 0.02-0.24) and primary physicians (OR = 0.24; 95% CI, 0.09-0.69) were associated with decreased likelihood; and obsessive compulsive disorder and personality disorder (OR = 7.56; 95% CI, 1.75-32.69) were associated with increased likelihood of antipsychotic prescription. Conclusion: Less than 4% of the elderly visits with depression were prescribed atypical antipsychotics. Both clinical and demographic factors contribute to antipsychotic prescribing in elderly patients with depression.
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BackgroundA recent large database analysis raised concerns of potential acute kidney injury (AKI) risk associated with antipsychotics. However, whether individual atypical and typical antipsychotics are associated with differential AKI risks has not been investigated. Objective The current study compared the risks of AKI and known causes of AKI associated with a broad range of atypical and typical antipsychotics. Method This retrospective cohort analysis used January 2007–June 2013 US nationwide Humana claims data to define episodes of antipsychotic drug therapy for patients with schizophrenia and bipolar disorder. Study drugs were aripiprazole, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Study outcomes were hospitalizations with AKI, and known causes of AKI, i.e., hypotension, acute urinary retention, neuroleptic malignant syndrome/rhabdomyolysis, and pneumonia. AKI was the primary outcome of the study. Cox regressions using haloperidol as the baseline comparator were used to estimate the impact of alternative antipsychotics on the risks of study adverse events following the initiation of treatment. The Cox models controlled for treatment history, comorbidities, and concomitant drug use in the prior 6 months. They also controlled for patient demographics and dose of current treatment. ResultsThe overall incidence of AKI was 25.0 per 1000 person-years. According to our multivariate regression results, the risk of AKI was significantly increased in patients taking olanzapine [hazard ratio (HR) 1.344, 95% confidence interval (CI) 1.057–1.708], quetiapine (HR 1.350, 95% CI 1.082–1.685), and ziprasidone (HR 1.338, 95% CI 1.035–1.729) relative to haloperidol. Aripiprazole (HR 1.152, 95% CI 0.908–1.462) and risperidone (HR 1.147, 95% CI 0.923–1.426) had insignificantly higher risks of AKI compared with haloperidol, whereas fluphenazine (HR 0.729, 95% CI 0.483–1.102) had an insignificantly lower risk of AKI. When compared between drug classes, atypical antipsychotics had a significantly higher risk of AKI (HR 1.313, 95% CI 1.083–1.591) than typical antipsychotics. Conclusions Antipsychotics are associated with differential AKI risks, with several atypical antipsychotics having higher risks than haloperidol. However, the overall incidence of AKI was moderate, and AKI risk should only raise concern for clinicians with elderly patients or patients who are vulnerable to kidney disease.
Article
Background: Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. Aims of the study: To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Methods: Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOSTM database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to 10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. Results: There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Discussion: Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties regularly prescribing a therapeutic category, some physicians rely heavily on a small number of agents. Implications for health policies, health care provision and use: Health systems may need to offer educational interventions to clinicians in order to improve their ability to tailor treatment decisions to the needs of individual patients. Implications for future research: Future studies should examine the impact of the diversity of antipsychotic prescribing to determine whether more diversified prescribing improves patient adherence and outcomes.
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Introduction: Antipsychotic drugs (APs) represent the mainstay of treatment for schizophrenia and other forms of psychosis. Tardive dyskinesia (TD) is a motor disorder associated with the ongoing use of APs and is characterized by involuntary, repetitive movements that are potentially irreversible. Current treatment is wanting, due in part to our limited understanding of the mechanisms underlying TD. Areas covered: Risk of TD associated with APs appears linked to continuous blockade of dopamine D2 receptors in the basal ganglia. Proposed mechanisms include increased dopamine activation of D2 receptors caused by supersensitivity and neurodegeneration of dopamine-producing neurons due to biochemical changes incurred by ongoing AP exposure. Existing treatments are designed to reverse or prevent the neurochemical/biological changes caused by dopamine D2 receptor blockade and include vesicular monoamine transporter (VMAT) inhibitors, antioxidants, compounds with serotonin receptor agonism as well as antagonism, GABA agonists and cholinergic agents. Randomized, controlled trials in Phase II and Phase III (ClinicalTrials.org/ClinicalTrialsRegister.eu) are summarized and discussed. Expert opinion: Effective adjunctive treatment for the symptoms of TD will depend on gaining a better understanding of the neurological changes induced by chronic dopamine D2 receptor antagonism from APs.
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Objective: The study examined changes in French general practitioners' (GPs) antipsychotic preferences between 2003 and 2010, a period when evidence challenging the superiority and safety of second-generation antipsychotics was introduced. Methods: Data from the IMS Health Disease Analyzer database for a cohort of 347 GPs (with 12 or more antipsychotic prescriptions in 2003 and in 2010) were used. For each year and GP, preferred antipsychotic was defined as the drug most frequently prescribed at the patient level. Trends in mean number of prescriptions, preferred drug, and changes in preferred antipsychotic class were documented. Results: The mean annual number of antipsychotic prescriptions increased over the period (p<.001). The percentage of GPs who preferred a second-generation antipsychotic tripled, from 16% in 2003 to 50% in 2010. In 2010, 42% of GPs who preferred first-generation antipsychotics in 2003 had switched their preference to second-generation antipsychotics. Conclusions: GPs' preferences for antipsychotics changed dramatically between 2003 and 2010.
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This article shows that Medical Innovation—the landmark study by Coleman, Katz, and Menzel—and several subsequent studies analyzing the diffusion of the drug tetracycline have confounded social contagion with marketing effects. The article describes the medical community's understanding of tetracycline and how the drug was marketed. This situational analysis finds no reasons to expect social contagion; instead, aggressive marketing efforts may have played an important role. The Medical Innovation data set is reanalyzed and supplemented with newly collected advertising data. When marketing efforts are controlled for, contagion effects dis- appear. The article underscores the importance of controlling for potential confounds when studying the role of social contagion in innovation diffusion.
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Pharmaceutical firms heavily promote their products and may have changed marketing strategies in response to reductions in new product approvals, restrictions on some forms of promotion, and the expanding role of biologic therapies. We used descriptive analyses of annual cross-sectional data from 2001 through 2010 to examine direct-to-consumer advertising (DTCA) (Kantar Media) and provider-targeted promotion (IMS Health and SDI), including: (1) inflation-adjusted total promotion spending ($ and percent of sales); (2) distribution by channel (consumer v. provider); and (3) provider specialty both for the industry as a whole and for top-selling biologic and small molecule therapies. Total promotion peaked in 2004 at US$36.1 billion (13.4% of sales). By 2010 it had declined to $27.7B (9.0% of sales). Between 2006 and 2010, similar declines were seen for promotion to providers and DTCA (both by 25%). DTCA's share of total promotion increased from 12% in 2002 to 18% in 2006, but then declined to 16% and remains highly concentrated. Number of products promoted to providers peaked in 2004 at over 3000, and then declined 20% by 2010. In contrast to top-selling small molecule therapies having an average of $370 million (8.8% of sales) spent on promotion, top biologics were promoted less, with only $33 million (1.4% of sales) spent per product. Little change occurred in the composition of promotion between primary care physicians and specialists from 2001-2010. These findings suggest that pharmaceutical companies have reduced promotion following changes in the pharmaceutical pipeline and patent expiry for several blockbuster drugs. Promotional strategies for biologic drugs differ substantially from small molecule therapies.
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Physicians prescribing drugs for patients with schizophrenia and related conditions are remarkably concentrated in their choice among antipsychotic drugs. In 2007 the single antipsychotic drug prescribed by a physician accounted for 66% of all antipsychotic prescriptions written by that physician. Which particular branded antipsychotic was the prescriber's "favorite" varied widely across physicians, i.e. physician prescribing concentration patterns are diverse. Building on Frank and Zeckhauser's [2007] characterization of physician treatments varying from "custom made" to "ready-to-wear", we construct a model of physician learning that generates a number of hypotheses. Using 2007 annual antipsychotic prescribing behavior on 17,652 physicians from IMS Health, we evaluate these predictions empirically. While physician prescribing behavior is generally quite concentrated, prescribers having greater volumes, those with training in psychiatry, male prescribers, and those not approaching retirement age tend to have less concentrated prescribing patterns.Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.
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Sources of regional variation in spending for prescription drugs under Medicare Part D are poorly understood, and such variation may reflect differences in health status, use of effective treatments, or selection of branded drugs over lower-cost generics. We analyzed 2008 Medicare data for 4.7 million beneficiaries for prescription-drug use and expenditures overall and in three drug categories: angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), and selective serotonin-reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Differences in per capita expenditures across hospital-referral regions (HRRs) were decomposed into annual prescription volume and cost per prescription. The ratio of prescriptions filled as branded drugs to all prescriptions filled was calculated. We adjusted all measures for demographic, socioeconomic, and health-status differences. Mean adjusted per capita pharmaceutical spending ranged from $2,413 in the lowest to $3,008 in the highest quintile of HRRs. Most (75.9%) of that difference was attributable to the cost per prescription ($53 vs. $63). Regional differences in cost per prescription explained 87.5% of expenditure variation for ACE inhibitors and ARBs and 56.3% for statins but only 36.1% for SSRIs and SNRIs. The ratio of branded-drug to total prescriptions, which correlated highly with cost per prescription, ranged across HRRs from 0.24 to 0.45 overall and from 0.24 to 0.55 for ACE inhibitors and ARBs, 0.29 to 0.60 for statins, and 0.15 to 0.51 for SSRIs and SNRIs. Regional variation in Medicare Part D spending results largely from differences in the cost of drugs selected rather than prescription volume. A reduction in branded-drug use in some regions through modification of Part D plan benefits might lower costs without reducing quality of care. (Funded by the National Institute on Aging and others.).
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In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of atypical anti psychotic use among elderly patients with dementia. The impact of these warnings on atypical drug use is unknown. We used quasi-experimental, interrupted time-series analyses to examine nationally representative data from IMS Health's National Disease and Therapeutic Index from January 2003 through December 2008. The primary measurement from this audit of office-based physicians was the use of an atypical antipsychotic agent. We quantified the impact of the advisory on atypical antipsychotic use among all individuals and those 65 years or older with dementia. From January 2003 to March 2005, mentions of total atypical antipsychotic drugs increased at an annual rate of 34%, and among patients with dementia, 16%. In the year prior to the FDA advisory, there were approximately 13.6 million atypical drug mentions, including 0.8 million among those with dementia. In the year following the advisory, atypical drug mentions fell 2% overall and 19% among those with dementia. In 2004, 19% (0.8 of 4.1 million) of drug mentions for dementia were for an atypical agent. By 2008, this proportion decreased to 9% (0.4 of 4.3 million). Atypical drug use slowed for both FDA-approved and off-label indications and declined through 2008 for all populations examined. The FDA advisory was associated with decreases in the use of atypical antipsychotics, especially among elderly patients with dementia.
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The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was funded by the National Institute of Mental Health to compare the effectiveness of drugs for schizophrenia. The focus here is not on its conclusions but on the knotty issues of design and methods, in order to support appropriate clinical interpretation of the conclusions, and on using the CATIE experience to indicate directions for improvement of future clinical trials. While many of the CATIE design and implementation decisions are excellent and serve as models for future research, other decisions resulted in a study with a large study group but inadequate power. Multiple treatment interventions, unbalanced randomization within and across clinical sites, and multiple secondary outcomes are among the issues that require even more serious consideration in future large multisite clinical trials. Moreover, it is crucial to clarify whether the intent of a study is to establish superiority of some treatments or to establish equivalence, for the appropriate designs and analyses differ in these situations. If the study is designed, as was CATIE, to demonstrate some treatments' superiority, statistically nonsignificant results should not be misinterpreted as evidence of "equivalence." For establishing either superiority or equivalence, future treatment comparisons might better be designed with fewer sites, more subjects per site, fewer treatments, and fewer outcomes, in order to have the power for definitively establishing superiority or equivalence at a lower cost.
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This study aimed to determine the prevalence of prescribing antipsychotics to adults without schizophrenia or bipolar disorder and to identify factors associated with such off-label use. Patients with at least one prescription for an antipsychotic medication from the Department of Veterans Affairs (VA) during fiscal year (FY) 2007 were identified in national VA administrative databases. Rates of off-label antipsychotic use were determined along with average doses. Multivariate logistic regression models identified sociodemographic and clinical characteristics associated with off-label use. Of the 279,778 individuals in FY 2007 who received an antipsychotic medication, 168,442 (60.2%) had no record of a diagnosis for which these drugs are approved. The most common mental illness diagnoses among patients given prescriptions for antipsychotics off label were posttraumatic stress disorder (PTSD, 41.8%), minor depression (39.5%), major depression (23.4%), and anxiety disorder (20.0%). Among VA patients with mental illness other than schizophrenia or bipolar disorder, the proportion who received prescriptions for antipsychotic medications ranged from a low of 9.1% among patients with adjustment reaction; to about 20% for those with depression, dementia, or PTSD; and to a high of 40.7% among patients with other psychoses. Doses were low, with over half of patients who received off-label quetiapine, risperidone, or first-generation antipsychotics receiving doses below those recommended for schizophrenia. In logistic regression models, patients diagnosed as having other psychosis or dementia had the highest odds of receiving an antipsychotic medication off label. Off-label use of antipsychotic medications was common. Given that these drugs are expensive, have potentially severe side effects, and have limited evidence supporting their effectiveness for off-label usage, they should be used with greater caution.
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In 2006, six million beneficiaries who were eligible for both Medicare and Medicaid switched from Medicaid to Medicare Part D for coverage of their prescription drugs. This change led to an expanded role for Medicare in financing psychotropic medications for dual eligibles. A reduction in the number of plans serving these beneficiaries and an increase in utilization restrictions for some psychotropics since 2006 raise concerns about access to medications for dual eligibles with mental disorders and point to potential problems with adverse selection. To improve access for this population, Medicare might consider changes to its enrollment and risk-sharing systems.
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To explore consultants' and general practitioners' perceptions of the factors that influence their decisions to introduce new drugs into their clinical practice. Qualitative study using semistructured interviews. Monitoring of hospital and general practice prescribing data for eight new drugs. Teaching hospital and nearby general hospital plus general practices in Birmingham. Participants: 38 consultants and 56 general practitioners who regularly referred to the teaching hospital. Reasons for prescribing a new drug; sources of information used for new drugs; extent of contact between consultants and general practitioners; and amount of study drugs used in hospitals and by general practitioners. Consultants usually prescribed new drugs only in their specialty, used few new drugs, and used scientific evidence to inform their decisions. General practitioners generally prescribed more new drugs and for a wider range of conditions, but their approach varied considerably both between general practitioners and between drugs for the same general practitioner. Drug company representatives were an important source of information for general practitioners. Prescribing data were consistent with statements made by respondents. The factors influencing the introduction of new drugs, particularly in primary care, are more multiple and complex than suggested by early theories of drug innovation. Early experience of using a new drug seems to strongly influence future use.
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The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies. The authors' goal was to assess the effects of clozapine, olanzapine, risperidone, and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a randomized double-blind 14-week trial. One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were inpatients at four hospitals were originally included in the study. The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period. Planned assessments included fasting glucose and cholesterol, which were collected at baseline and at the end of the 8-week period and the following 6-week period. One hundred eight of the 157 patients provided blood samples at baseline and at least at one point after random assignment to clozapine, olanzapine, risperidone, or haloperidol during the treatment trial. Seven of these patients had diabetes; their glucose levels were >125 mg/dl at baseline. Data from 101 patients were used for statistical analyses. During the initial 8-week period there was an overall significant increase in mean glucose levels. There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine (N=27) and those given haloperidol (N=25). The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period (N=22). Fourteen of the 101 patients developed abnormal glucose levels (>125 mg/dl) during the trial (six with clozapine, four with olanzapine, three with risperidone, and one with haloperidol). Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine (N=27) and those given olanzapine (N=26); cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine (N=22). In this prospective randomized trial, clozapine, olanzapine, and haloperidol were associated with an increase of plasma glucose level, and clozapine and olanzapine were associated with an increase in cholesterol levels. The mean changes in glucose and cholesterol levels remained within clinically normal ranges, but approximately 14% of the patients developed abnormally high glucose levels during the course of their participation in the study.
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States are reacting to increased Medicaid drug costs by implementing cost-control policies, such as preferred drug lists (PDLs) and prior authorization. PDLs have risks as well as benefits. Targeting essential drug classes with heterogeneous patient responses and side effects could reduce appropriate care, adversely affect health status, and cause shifts to more costly types of care. Assessing inappropriate use of high-cost drugs before implementing regulations and instituting simple mechanisms to exempt high-risk patients could maximize savings and minimize harm. The current exponential growth in such policies and the limited evidence base justifies investment in research to identify which policies can achieve savings without unintended consequences.
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Although innovative drugs may be underprescribed by some physicians, it is possible that rapid adoption after market introduction may lead to prescribing such drugs to patients without a clear indication. We sought to quantify the relative contributions of patient vs. physician factors to the decision to prescribe selective cyclooxygenase-2 (COX-2) inhibitors during the first 2 years of their availability. A cohort of 37,957 Medicare beneficiaries who were enrolled in the Pharmaceutical Assistance Contract for the Elderly in Pennsylvania was identified. All patients had started using nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors between January 1, 1999, and December 31, 2000, and had no prior NSAID use. All had full prescription drug coverage, including NSAIDs and selective COX-2 inhibitors. Subsequent prescriptions were not considered. We quantified the amount of variation in first-time COX-2 prescribing that could be explained by predictors of gastrointestinal (GI) toxicity, other patient characteristics, or physician preferences. Explained variation was calculated as the R(2) (standardized to range from 0 to 1) from unconditional logistic regression and random intercept mixed effects logistic regression, fitted separately in each of eight consecutive 3-month periods. COX-2 inhibitors were adopted as the preferred NSAID by 55% of physicians within 180 days after they were marketed. In new NSAID users, COX-2 prescribing was twice as dependent on physician prescribing preferences (R(2)=60%) as on the combined predictors of GI toxicity (R(2)=3%) and other patient factors (R(2)=30%). The ratio of COX-2 prescribing explained by physician preferences over the contribution of patient factors increased from 2 to more than 10 over a 24-month period. First-time COX-2 inhibitor prescribing was somewhat dependent on patient factors in the first quarter of marketing, but the proportional influence of physician preferences increased substantially over the following 2 years, raising the question of why physician factors and not patient risk factors influence COX-2 inhibitor prescribing.
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The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.
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When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.
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Second-generation antipsychotics have largely replaced first-generation antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of four second-generation drugs (olanzapine, quetia-pine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to perphenazine. The cost analysis included medications plus health services use. Quality-adjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-to-treat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between perphenazine and any second-generation medication. Average total monthly health care costs were 300 dollars-600 dollars (20%-30%) lower for perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. Treatment with perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.
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Current health policies assume that prescribing is more efficient and rational when general practitioners (GPs) work with a formulary or restricted drugs lists and thus with a limited range of drugs. Therefore we studied determinants of the range of drugs prescribed by general practitioners, distinguishing general GP-characteristics, characteristics of the practice setting, characteristics of the patient population and information sources used by GPs. Secondary analysis was carried out on data from the Second Dutch Survey in General Practice. Data were available for 138 GPs working in 93 practices. ATC-coded prescription data from electronic medical records, census data and data from GP/practice questionnaires were analyzed with multilevel techniques. The average GP writes prescriptions for 233 different drugs, i.e. 30% of the available drugs on the market within one year. There is considerable variation between ATC main groups and subgroups and between GPs. GPs with larger patient lists, GPs with higher prescribing volumes and GPs who frequently receive representatives from the pharmaceutical industry have a broader range when controlled for other variables. The range of drugs prescribed is a useful instrument for analysing GPs' prescribing behaviour. It shows both variation between GPs and between therapeutic groups. Statistically significant relationships found were in line with the hypotheses formulated, like the one concerning the influence of the industry. Further research should be done into the relationship between the range and quality of prescribing and the reasons why some GPs prescribe a greater number of different drugs than others.
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Two large, non-commercial clinical trials comparing first- and second-generation antipsychotic drugs for people with chronic schizophrenia in the US and UK have shown unexpected results. in general, the newer drugs were no more effective or better tolerated than the older drugs. Clozapine outperformed other second-gene ration drugs. The implications are considered. Declaration of interest S.L. is the Chief investigator of the CUtLASS study and J.L. is the Chief Investigator of the CATIE study, S.L. has received honoraria from several pharmaceutical companies. J.L. has received research funding from several pharmaceutical companies.
Article
Objective: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. Method: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N= 15], or risperidone [N=16]). Results: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median= 3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. Conclusions: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.
Article
Although direct-to-consumer advertising (DTCA) has generated substantial controversy, little is known about its effects on consumer and physician behavior. In this article, the authors examine the impact of DTCA and physician detailing on the choice of antidepressant medication. The authors find that detailing has a much greater effect on medication choice in the antidepressant market than does DTCA.
Article
The SGAs are of great benefit to a wide variety of people with psychiatric disorders. As with all drugs, SGAs are associated with undesirable side effects. One constellation of adverse effects is an increased risk for obesity, diabetes, and dyslipidemia. The etiology of the increased risk for metabolic abnormalities is uncertain, but their prevalence seems correlated to an increase in body weight often seen in patients taking an SGA. Direct drug effects on β-cell function and insulin action could also be involved, since there is insufficient information to rule out this possibility. In the general population, being overweight or obese also carries a much higher risk of diabetes and dyslipidemia. These three adverse conditions are closely linked, and their prevalence appears to differ depending on the SGA used. Clozapine and olanzapine are associated with the greatest weight gain and highest occurrence of diabetes and dyslipidemia. Risperidone and quetiapine appear to have intermediate effects. Aripiprozole and ziprasidone are associated with little or no significant weight gain, diabetes, or dyslipidemia, although they have not been used as extensively as the other agents. The choice of SGA for a specific patient depends on many factors. The likelihood of developing severe metabolic disease should also be an important consideration. When prescribing an SGA, a commitment to baseline screening and follow-up monitoring is essential in order to mitigate the likelihood of developing CVD, diabetes, or other diabetes complications.
Article
Objective: Second-generation antipsychotics captured most of the U.S. antipsychotic market shortly after their introduction. Little is known about how second-generation antipsychotics have diffused in other countries with different health systems. The study objective was to describe trends in antipsychotic use in the United States and France from 1998 to 2008. Methods: Pharmaceutical policies in France and the United States are briefly described, followed by descriptive data on quarterly prescriptions for oral antipsychotics dispensed between January 1998 and September 2008. Data are from Xponent for the United States and the GERS database for France. Trends in the use of first- versus second-generation antipsychotics and in ingredient formulations of second-generation antipsychotics used are reported. Results: Between 1998 and 2008, total antipsychotic use in the United States increased by 78%. Total use in France was consistently higher despite a 9% decrease during the period. By 2008, second-generation antipsychotics represented 86% of the antipsychotics sold in the U.S. market, versus only 40% of the French market. However, average annual growth rates in use of second-generation antipsychotics were similar in the two countries. In France, use of all but one second-generation antipsychotic steadily increased, whereas in the United States trends in the use of newer drugs varied substantially by drug. For example, use of olanzapine decreased after 2003, but use of quetiapine increased. Conclusions: These results highlight markedly divergent trends in the diffusion of new antipsychotics in France and the United States. Some differences may be explained by differences in health systems; others may reflect physicians' preferences and norms of practice.
Article
There has been a substantial increase in the number of patients suffering from psychiatric disorders who seek treatment in primary care practices, which has precipitated an increase in the number of pre-scriptions written by primary care physicians for psychotropic agents. As managed care has become entrenched in communities, many patients presenting with psychiatric disorders are seeking help from primary care physicians because mental health coverage offered by many managed care companies is deemed to be inadequate. There currently exists considerable variation in prescribing patterns of psychotropic medications between primary care providers and psychiatrists and among primary care physicians themselves, as well as a general lack of concordance between diagnoses and psychotropic medications prescribed in the medical field as a whole. Prescribing patterns vary due to differences in diagnoses, the discomfort that some primary care physicians feel toward prescribing psychotropic medications, differing levels of awareness and recognition due to cultural variances, the perceived negative stigma of mental illness, and insufficient education regarding the etiology and management of psychiatric disorders. These variations are particularly evident in the prescribing trends of antipsy-chotic medications by primary care physicians. (Primary Care Companion J Clin Psychiatry 2003;5[suppl 3]:3–8) t the end of the 1980s, of all the patients in primary care, 25% to 30% had a psychiatric disorder. tween the available agents. To positively impact patient populations, it is important for primary care physicians to understand how to identify mental illnesses in their patients and how to effectively use various medications to manage the spectrum of these disorders that now are so frequently presenting in their practices.
Article
Objectives The objective of this study was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centred and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. Methods A cross-sectional secondary data analysis was carried out, examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligibility Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternative measures of prescribing concentration: (1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens and (2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. Key findings In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (P < 0.05). The Herfindahl index measure showed a trend towards a similar inverse relationship (P < 0.10). Conclusions The findings provide some support for the hypothesized relationship between prescribing variation and adequate antidepressant treatment duration during the acute phase of treatment. Future work with more detailed, clinical longitudinal data could extend this inquiry to better understand the causal mechanisms using a more direct measure of customized care.
Article
Widely accepted treatment guidelines and performance measures encourage patients to stay on antidepressant medication beyond the acute phase of treatment in order to achieve full remission and reduce risk of relapse. However, many patients discontinue antidepressant medication treatment prematurely for various reasons, including side-effects or nonresponse to the initial medication prescribed. Customization of medications to differing patient profiles could potentially improve medication treatment duration, but for many diseases physicians tend to concentrate on a limited subset of available medications. Little is known about the effects of concentration in prescribing on medication treatment duration and expenditures. To determine the extent to which prescribing for treatment of depression is concentrated, using data from a privately insured population. To evaluate the relationship between prescribing concentration and subsequent duration of medication treatment, expenditure on medications, and the number of distinct medications used. Individuals receiving antidepressant treatment paid for by a large private managed behavioral health organization, in the US. The study uses psychotropic pharmacy claims data for 2003-06 for plan members who received a depression diagnosis and had an antidepressant claim. The resulting sample includes 9,017 patients seen by 543 prescribers. For each prescriber, we compute prescribing concentration, using the Herfindahl index and the share for the three most-used medications. Treatment expenditure is computed as the sum of payments by plan and by patients. Regression analysis is used to identify the association of prescribing concentration with medication treatment duration, expenditures and other utilization measures. For these physicians, the mean share of the physician's total antidepressant prescribing accounted for by their three most-used regimens was 72%. The mean value of the Herfindahl index was 0.27. Over the 180-day follow-up period, the average patient had 103 days covered by antidepressant prescriptions, resulting in mean expenditures of $286, or $2.25 per day of medication supplied. Regression analysis indicates that higher concentration in a physician's prescribing was associated with fewer days of antidepressant coverage, lower medication expenditures, and subsequent use of fewer distinct medications. Higher concentration in prescribing is associated with shorter observed duration of medication treatment and lower expenditures on medications. The lower expenditures appear to be due to earlier discontinuation and fewer different medications, not to a lower cost per day supplied. Limitations of this study include lack of data on medical visits or on reasons for medication discontinuation, as the study is based on pharmacy claims data, not medical claims or surveys. In addition, it is not known whether the patient's antidepressant use represents a new episode. Finally, lack of randomization implies that the associations identified may not be causal. Concentration of physicians on certain medications may run counter to the increasing calls for customization of medication selection. Insurer policies which limit physicians' choice of medications may be lowering expenditures in part by reducing patients' medication treatment duration. Additional studies are needed to understand what mechanisms may link concentration in prescribing to medication treatment duration and expenditures.
Article
For many disorders, patient heterogeneity requires physicians to customize their treatment to each patient's needs. We test for the existence of customization in physicians' prescribing for bipolar disorder, using data from a naturalistic clinical effectiveness trial of bipolar disorder treatment (STEP-BD), which did not constrain physician prescribing. Multinomial logit is used to model the physician's choice among five combinations of drug classes. We find that our observed measure of the patient's clinical status played only a limited role in the choice among drug class combinations, even for conditions such as mania that are expected to affect class choice. However, treatment of a patient with given characteristics differed widely depending on which physician was seen. The explanatory power of the model was low. There was variation within each physician's prescribing, but the results do not suggest a high degree of customization in physicians' prescribing, based on our measure of clinical status.
Article
This study compared the clinical characteristics, use of guideline-concordant pharmacotherapy, and outcomes of patients diagnosed as having bipolar disorder who were exclusively seen in Department of Veteran Affairs (VA) primary care settings with those of patients with bipolar disorder who received any VA mental health services. Data from the 1999 Large Health Survey of Veterans were linked to VA data from the National Psychosis Registry to identify patients diagnosed as having bipolar disorder (N=14,643). Multivariable analyses adjusting for sociodemographic characteristics and clinical and severity factors determined whether exclusive primary care use versus any mental health care use was associated with poor clinical and services outcomes. Overall, 7.6% used primary care services exclusively. Compared with persons who used specialty care services, those who used primary care exclusively were more likely to be diagnosed as having cardiovascular disease (odds ratio [OR]=1.26, p<.05) or hypertension (OR=1.31, p<.01), less likely to receive guideline-concordant pharmacotherapy (OR=.18, p<.001), more likely to have an inpatient medical visit (OR=1.36, p<.01), and less likely to have an inpatient psychiatric visit (OR=.36, p<.001). Persons who received only primary care were more likely to have worse physical health and better mental health, as measured by the 36-Item Short-Form Health Survey. Patients with bipolar disorder treated in primary care settings were more likely than those who received some care in a mental health specialty setting to have comorbid general medical disorders. Optimal care settings for patients with bipolar disorder may require strategies that address gaps in general medical as well as psychiatric care.
Article
Psychotropic medication polypharmacy is common in psychiatric outpatient settings and, in some patient groups, may have increased in recent years. To examine patterns and recent trends in psychotropic polypharmacy among visits to office-based psychiatrists. Annual data from the 1996-2006 cross-sectional National Ambulatory Medical Care Surveys were analyzed to examine patterns and trends in psychotropic polypharmacy within nationally representative samples of 13 079 visits to office-based psychiatrists. Office-based psychiatry practices in the United States. Outpatients with mental disorder diagnoses visiting office-based psychiatrists. Number of medications prescribed in each visit and specific medication combinations. There was an increase in the number of psychotropic medications prescribed across years; visits with 2 or more medications increased from 42.6% in 1996-1997 to 59.8% in 2005-2006; visits with 3 or more medications increased from 16.9% to 33.2% (both P < .001). The median number of medications prescribed in each visit increased from 1 in 1996-1997 to 2 in 2005-2006 (mean increase: 40.1%). The increasing trend of psychotropic polypharmacy was mostly similar across visits by different patient groups and persisted after controlling for background characteristics. Prescription for 2 or more antidepressants, antipsychotics, sedative-hypnotics, and antidepressant-antipsychotic combinations, but not other combinations, significantly increased across survey years. There was no increase in prescription of mood stabilizer combinations. In multivariate analyses, the odds of receiving 2 or more antidepressants were significantly associated with a diagnosis of major depression (odds ratio [OR], 3.44; 99% confidence interval [CI], 2.58-4.58); 2 or more antipsychotics, with schizophrenia (OR, 6.75; 99% CI, 3.52-12.92); 2 or more mood stabilizers, with bipolar disorder (OR, 15.46; 99% CI, 6.77-35.31); and 2 or more sedative-hypnotics, with anxiety disorders (OR, 2.13; 99% CI, 1.41-3.22). There has been a recent significant increase in polypharmacy involving antidepressant and antipsychotic medications. While some of these combinations are supported by clinical trials, many are of unproven efficacy. These trends put patients at increased risk of drug-drug interactions with uncertain gains for quality of care and clinical outcomes.
Article
In 2003, the Food and Drug Administration (FDA) required a warning on diabetes risk for second-generation antipsychotic (SGA) drugs. The American Diabetes Association (ADA) and American Psychiatric Association (APA) recommended glucose and lipid testing for all patients starting to receive SGA drugs. To characterize associations between the combined warnings and recommendations and baseline metabolic testing and SGA drug selection. Interrupted time-series analysis. California, Missouri, and Oregon. Patients A total of 109 451 individuals receiving Medicaid who began taking SGA medication and a control cohort of 203 527 patients who began taking albuterol but did not receive antipsychotic medication. Prewarning and postwarning trends in metabolic testing were compared using laboratory claims for the cohort collected January 1, 2002, through December 31, 2005. Changes in SGA prescribing practices were similarly evaluated. Monthly rates of baseline serum glucose and lipid testing for SGA-treated and propensity-matched albuterol-treated patients and monthly share of new prescriptions for each SGA drug. Initial testing rates for SGA-treated patients were low (glucose, 27%; lipids, 10%). The warning was not associated with an increase in glucose testing among SGA-treated patients and was associated with only a marginal increase in lipid testing rates (1.7%; P = .02). Testing rates and trends in SGA-treated patients were not different from background rates observed in the albuterol control group. New prescriptions of olanzapine (higher metabolic risk) declined during the warning period (annual share decline, 19.9%; P < .001). New prescriptions of aripiprazole (lower metabolic risk) increased during the warning period (share increase, 12.1%; P < .001) but may be attributable to the elimination of prior authorization in California during the same time frame. Quetiapine, risperidone, and ziprasidone use were not associated with the warning. In a Medicaid-receiving population, baseline glucose and lipid testing for SGA-treated patients was infrequent and showed little change following the diabetes warning and monitoring recommendations. A change in SGA drug selection consistent with intentions to reduce metabolic risk was observed.
Article
Cardiometabolic effects of second-generation antipsychotic medications are concerning but have not been sufficiently studied in pediatric and adolescent patients naive to antipsychotic medication. To study the association of second-generation antipsychotic medications with body composition and metabolic parameters in patients without prior antipsychotic medication exposure. Nonrandomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted between December 2001 and September 2007 at semi-urban, tertiary care, academic inpatient and outpatient clinics in Queens, New York, with a catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1 week or less of antipsychotic medication exposure, 338 were enrolled (66.9%). Of these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205 patients [corrected] completed the study (60.7%). Patients had mood spectrum (n = 130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused participation or were nonadherent served as a comparison group. Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks. Weight gain and changes in lipid and metabolic parameters. After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, -1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P < .001 and 9.1 mg/dL [95% CI, 0.4 to 17.7 mg/dL] P = .046), triglycerides (24.3 mg/dL [95% CI, 9.8 to 38.9 mg/dL] P = .002 and 37.0 mg/dL [95% CI, 10.1 to 63.8 mg/dL] P = .01), non-high-density lipoprotein (HDL) cholesterol (16.8 mg/dL [95% CI, 9.3 to 24.3 mg/dL] P < .001 and 9.9 mg/dL [95% CI, 1.4 to 18.4 mg/dL] P = .03), and ratio of triglycerides to HDL cholesterol (0.6 [95% CI, 0.2 to 0.9] P = .002 and (1.2 [95% CI, 0.4 to 2.0] P = .004). With risperidone, triglycerides increased significantly (mean level, 9.7 mg/dL [95% CI, 0.5 to 19.0 mg/dL]; P = .04). Metabolic baseline-to-end-point changes were not significant with aripiprazole or in the untreated comparison group. First-time second-generation antipsychotic medication use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotic medications.
Article
It is unknown to what extent providers utilize the full range of available antipsychotic agents, or tend to prescribe just a few with which they are familiar. This study uses the Herfindahl index to measure the degree to which antipsychotic prescribing is diverse or concentrated within medical centers in the Department of Veterans Affairs. Patients with schizophrenia who received prescriptions for antipsychotic medications from the Department of Veterans Affairs in fiscal year 2005 were identified. For each facility, the proportion of prescriptions that were written for each antipsychotic medication was computed. The Herfindahl index, which is defined as the sum of the square of the proportionate shares of each medication (i.e., 50% squared = 0.25), was computed for each facility, and its distribution across facilities was examined. We identified 785,485 prescriptions for antipsychotic medications across 76,787 patients within 128 facilities. With 7 drugs to choose from (first-generation antipsychotics were not differentiated as separate drugs), the Herfindahl could range from 0.14 (if the drugs were prescribed equally) to 1 (if only 1 drug was prescribed to all patients). The Herfindahl averaged 0.20 to 0.21 and ranged from 0.16 to 0.31 across facilities. The Herfindahl index is a useful metric for describing the degree to which providers use a range of antipsychotic medications in treating patients with schizophrenia and suggests that VA facilities use a diversity of agents, thus taking advantage of the potentially unique drug-patient matches. The extent to which providers tailor their choice of antipsychotic medication to the particular characteristics of the patient may lead to better quality of care. The fact that providers do use a range of antipsychotic medications suggests that formulary policies should not reduce access to these drugs. Further research is needed to construct physician-level measures of prescribing diversity and to examine whether clinical outcomes are improved when providers use a wider range of medications in their practice.
Article
This study examined trends in the prescription of antipsychotic drugs in a nationally representative sample of physicians in nonfederal office-based clinical practice during the 1990s. The authors analyzed physician-reported data from annual National Ambulatory Medical Care Surveys between 1989 and 1997 using weighted national estimates of physician visits during which antipsychotic drugs were prescribed. Prescription rates for antipsychotic drugs were compared between periods and among demographic, organizational, and clinical subgroups. Prescription of antipsychotic drugs in office-based practice increased significantly between 1989 and 1997. In 1989 antipsychotics were prescribed during 3.2 million office visits (.46 percent of all visits), compared with 6.9 million visits in 1997 (.88 percent). The atypical antipsychotics risperidone and olanzapine were the most widely prescribed antipsychotics in 1997. Risperidone was prescribed during 22.8 percent of all visits that involved prescription of an antipsychotic, and olanzapine during 17.1 percent. Psychiatrists were more likely than other physicians to prescribe an atypical agent (37.1 percent of visits involving prescription of an antipsychotic compared with 14.2 percent). Psychiatrists were also more likely than other physicians to schedule a follow-up visit after prescribing an antipsychotic (96.6 percent of visits compared with 73 percent). No evidence was found of a broadening of diagnostic indications for use over time. The rate of prescription of antipsychotic drugs among office-based physicians increased sharply during the 1990s after a nine-year decline. The increase was accounted for by growth in the use of atypical antipsychotics; the overall prescription rate of conventional agents did not change. Psychiatrists were more likely to prescribe atypical agents and to monitor more closely patients who were taking antipsychotics.
Article
Many employers and health plans have adopted incentive-based formularies in an attempt to control prescription-drug costs. We used claims data to compare the utilization of and spending on drugs in two employer-sponsored health plans that implemented changes in formulary administration with those in comparison groups of enrollees covered by the same insurers. One plan simultaneously switched from a one-tier to a three-tier formulary and increased all enrollee copayments for medications. The second switched from a two-tier to a three-tier formulary, changing only the copayments for tier-3 drugs. We examined the utilization of angiotensin-converting-enzyme (ACE) inhibitors, proton-pump inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Enrollees covered by the employer that implemented more dramatic changes experienced slower growth than the comparison group in the probability of the use of a drug and a major shift in spending from the plan to the enrollee. Among the enrollees who were initially taking tier-3 statins, more enrollees in the intervention group than in the comparison group switched to tier-1 or tier-2 medications (49 percent vs. 17 percent, P<0.001) or stopped taking statins entirely (21 percent vs. 11 percent, P=0.04). Patterns were similar for ACE inhibitors and proton-pump inhibitors. The enrollees covered by the employer that implemented more moderate changes were more likely than the comparison enrollees to switch to tier-1 or tier-2 medications but not to stop taking a given class of medications altogether. Different changes in formulary administration may have dramatically different effects on utilization and spending and may in some instances lead enrollees to discontinue therapy. The associated changes in copayments can substantially alter out-of-pocket spending by enrollees, the continuation of the use of medications, and possibly the quality of care.
Article
The economic burden of depression was estimated to be 43.7 billion dollars in 1990. A subsequent study reported a cost burden of 52.9 billion dollars using revised prevalence data and a refined workplace cost estimation approach. The objective of the current report is to provide a 10-year update of these estimates using the same methodological framework. Using a human capital approach, we developed prevalence-based estimates of 3 major cost categories: (1) direct costs, (2) mortality costs arising from depression-related suicides, and (3) costs associated with depression in the workplace. Cost-of-illness estimates from 1990 were updated to reflect the experience in 2000 using current epidemiologic data and publicly available population, wage, and cost information. Whereas the treatment rate of depression increased by over 50%, its economic burden rose by only 7%, going from 77.4 billion dollars in 1990 (inflation-adjusted dollars) to 83.1 billion dollars in 2000. Of the 2000 total, 26.1 billion dollars (31%) were direct medical costs, 5.4 billion dollars (7%) were suicide-related mortality costs, and 51.5 billion dollars (62%) were workplace costs. The economic burden of depression remained relatively stable between 1990 and 2000, despite a dramatic increase in the proportion of depression sufferers who received treatment. Future research will incorporate additional costs associated with depression sufferers, including the excess costs of their coexisting psychiatric and medical conditions and attention to the role of painful conditions as a driver of these costs.
Article
We investigate the effect of initial provider (psychiatrist versus primary care physician or non-physician mental health specialist) on the adequacy of subsequent treatment for persons with depression. Our data are from MarketScan, a medical and pharmacy insurance claims database, which we use to estimate models of the likelihood of treatment for depression and the likelihood that any anti-depression treatments received are adequate. Patients initially seeing psychiatrists are most likely to receive adequate treatment. Provider type has a statistically and medically significant effect on whether any treatment occurs but a smaller effect on treatment adequacy among treated patients. Our results show the importance of provider type in treatment patterns, but the effects on patient outcomes are yet to be determined definitively.
Article
This study quantifies excess annual costs associated with schizophrenia patients in the United States in 2002 from a societal perspective. Annual direct medical costs associated with schizophrenia were estimated separately for privately (N = 1090) and publicly (Medicaid; N = 14,074) insured patients based on administrative claims data, including a large private claims database and the California Medicaid program (MediCal) database, and compared separately to demographically/geographically matched control samples (1 case:3 controls). Medicare costs of patients over age 65 years were imputed using the Medicare/MediCal dual-eligible patients (N = 1491) and published statistics. Excess annual direct non-health care costs were estimated for law enforcement, homeless shelters, and research/training related to schizophrenia. Excess annual indirect costs were estimated for 4 components of productivity loss: unemployment, reduced workplace productivity, premature mortality from suicide, and family caregiving using a human capital approach based on market wages. All costs were adjusted to 2002 dollars using the Medical Care Consumer Price Index and were based on the reported prevalence in the National Comorbidity Survey Replication. The overall U.S. 2002 cost of schizophrenia was estimated to be $62.7 billion, with $22.7 billion excess direct health care cost ($7.0 billion outpatient, $5.0 billion drugs, $2.8 billion inpatient, $8.0 billion long-term care). The total direct non-health care excess costs, including living cost offsets, were estimated to be $7.6 billion. The total indirect excess costs were estimated to be $32.4 billion. Schizophrenia is a debilitating illness resulting in significant costs. The indirect excess cost due to unemployment is the largest component of overall schizophrenia excess annual costs.
Article
There is a paucity of studies on U.S. national trends in the use of antipsychotic medications in the 21st century. This study examined national trends in the prescribing of antipsychotic drugs in office-based physician practices. National probability sample survey data from 1998-2002 National Ambulatory Medical Surveys were used to analyze the prescribing trends. The weighted visit estimates and percentages were compared across the years using z-test. The number of antipsychotic-related visits was found to increase significantly and nearly two-fold, from 4.6 million in 1998 to 8.6 million in 2002. During the same period, the number of visits for second-generation antipsychotic drugs nearly tripled. The proportion of visits for the second-generation agents, as a percentage of visits for all antipsychotic drugs, rose sharply from about 48% in 1998 to 84% in 2002. Correspondingly, the percentage of visits involving first-generation antipsychotic drugs declined. The growth in the number of visits involving antipsychotic drugs over the 5-year period was substantial (120%) in visits with non-psychiatrist physicians, but not in visits involving psychiatrists. The trend of growth in prescription of antipsychotic drugs in office visits, accounted by increased use of second-generation antipsychotics, has persisted into the 21st century. Increased prescribing of these agents by non-psychiatrists is also apparently fueling this trend. This trend of shift from first-to-second generation antipsychotic agents, though not unambiguously supported by extant safety and efficacy data, is endorsed by guidelines based on expert-consensus and limited data. Given the high-level use of second-generation drugs, more practical studies of these drugs, focusing on effectiveness or long-term outcomes, are needed.
Article
Empirical data indicate that patients seen in internal medicine outpatient settings have substantial rates of depression and other psychiatric disorders. Surprisingly, the training requirements established by the Residency Review Committee in Internal Medicine do not include a specific psychiatry training curriculum, but rather vaguely refer to "sufficient instruction and clinical experience" in psychiatry. In this study, internists on staff at a community hospital were surveyed to ascertain their general level of comfort with prescribing psychotropic medication. The study hypotheses were: (1) compared with other psychotropic medications, internists would generally be most comfortable with the prescription of antidepressants; (2) younger, rather than older, internists would be more comfortable with prescribing psychotropic medications; and (3) internists with greater outpatient, versus inpatient, responsibilities would be more comfortable with psychotropic medication prescription. This sample of internists demonstrated differences in prescribing comfort by medication group (F(3) = 48.99, p < .001) and was most comfortable in prescribing antidepressants and benzodiazepines, in contrast to antipsychotics and other types of psychotropic medications; comparing older with younger internists, there was a significant between-group difference in the mean number of medications positively endorsed, t(66) = 2.16, p <.05, with younger internists indicating broader comfort levels; and inpatient internists were significantly more comfortable prescribing antipsychotics than outpatient internists, t(117) = -3.38, p = .001. There are some distinct psychotropic prescription trends among internists, which have implications for future training and quality improvement programs.
Article
State Medicaid programs use prior authorization (PA) to control drug spending by requiring that specific conditions be met before allowing reimbursement. The extent to which PA policies respond to new developments concerning medication safety is not known. In April 2005 the Food and Drug Administration (FDA) issued an advisory describing increased mortality among elderly people with dementia taking atypical antipsychotics. More than a year later, no state had changed its PA policy in response. We discuss the roles of Medicaid and other insurers in responding to emerging drug safety issues and their challenges in weighing drug risks and benefits.
Article
We sought to understand how findings of the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS band 1)1 and their comparison with those from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study in schizophrenia2,3 clarify issues raised in our 2005 American Psychiatric Association annual meeting debate “Second-Generation Antipsychotics (SGAs) Are Uniformly Superior in Efficacy and Safety to First-Generation Antipsychotics (FGAs).”4 Applying the primary effectiveness metric used in CATIE to CUtLASS band 1 findings, we noted that in contrast to 60 of 118 patients (51%) assigned to receive an FGA who continually took an FGA through the 1-year study, 70 of 109 patients (64%) assigned to receive an SGA did so (χ21 = 4.14; P < .05). In CUtLASS band 1, SGAs were found to be more effective than FGAs in terms of all-cause discontinuation. Despite this apparent SGA advantage in a nonblinded aspect of that study, results of both CATIE and CUtLASS band 1 indicate that FGAs are as effective as SGAs. How does one reconcile this observation with previous findings suggesting that SGAs are more effective than FGAs?
Article
To customize treatments to individual patients entails costs of coordination and cognition. Thus, providers sometimes choose treatments based on norms for broad classes of patients. We develop behavioral hypotheses explaining when and why doctors customize to the particular patient, and when instead they employ "ready-to-wear" treatments. Our empirical studies examining length of office visits and physician prescribing behavior find evidence of norm-following behavior. Some such behavior, from our studies and from the literature, proves sensible; but other behavior seems far from optimal.
Article
The publicly funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) did not support superiority hypotheses for second-generation antipsychotic drugs in schizophrenia. Instead, the study supported the view that first- and second-generation antipsychotics have similar therapeutic properties and diverse adverse effect profiles. This emphasizes the importance of designing pharmacotherapy for the individual in order to optimize the benefit-to-risk profile. First- and second-generation antipsychotic drugs are extensively similar in mechanism of action, efficacy for psychosis, and lack of efficacy for avolition and impaired cognition. However, adverse effect profiles vary between drugs. The authors review the clinical implications of these data, with an emphasis on individualizing pharmacotherapy in an effort to reduce risk. Rather than selecting drugs on the basis of unfounded expectations of superior efficacy, clinicians can focus on selecting drugs and optimizing dosages to minimize adverse effects without sacrificing efficacy. Tardive dyskinesia may be a good reason to avoid a high dosage of first-generation antipsychotics, although the evidence for differential risk is less compelling for a modest dosage of low-affinity first-generation antipsychotics. Similarly, the metabolic effects of some second-generation antipsychotics can be decisive in considering risks. In either case, the clinician should detect earliest signs and take action while dyskinetic or metabolic effects are most reversible. Bottom line: the dichotomy between first- and second-generation antipsychotics was not supported by efficacy data (and now, is not supported effectiveness data). Only clozapine has documented superiority in treatment-resistant cases.
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This paper studies the contribution of doctor and patient "habit" to persistence in market shares in prescription drug markets. My unique panel dataset allows me to estimate the probability of switching brands as a function of patient and doctor attributes, with an emphasis on past prescribing behaviour so as to capture the degree of persistence. I find significant evidence of time-dependence in prescription choices for both doctors and patients, which seems to imply that in molecular submarkets in which brands are not allowed to compete on the basis of price, doctor and patient "habit" at the micro-level can translate into sticky and persistent market shares at the aggregate level. Copyright 2000 by Blackwell Publishing Ltd
The economic burden of depression in the United States: how did it change between
  • P E Greenberg
  • R C Kessler
  • H G Birnbaum
Greenberg PE, Kessler RC, Birnbaum HG, et al: The economic burden of depression in the United States: how did it change between 1990 and 2000? Journal of Clinical Psychiatry 64:1465-1475, 2003
Prescription of antipsychotic drugs by officebased physicians in the United States
  • R C Hermann
  • D Yang
  • S L Ettner
Hermann RC, Yang D, Ettner SL, et al: Prescription of antipsychotic drugs by officebased physicians in the United States, 1989-1997. Psychiatric Services 53:425-430, 2002