Evaluation of Human Hepatocyte Drug Metabolism Carrying High-Risk or Protection-Associated Liver Disease Genetic Variants.

Metabolic-dysfunction-associated steatotic liver disease (MASLD), which affects 30 million people in the US and is anticipated to reach over 100 million by 2030, places a significant financial strain on the healthcare system. There is presently no FDA-approved treatment for MASLD despite its public health significance and financial burden. Understanding the connection between point mutations, liver enzymes, and MASLD is important for comprehending drug toxicity in healthy or diseased individuals. Multiple genetic variations have been linked to MASLD susceptibility through genome-wide association studies (GWAS), either increasing MASLD risk or protecting against it, such as PNPLA3 rs738409, MBOAT7 rs641738, GCKR rs780094, HSD17B13 rs72613567, and MTARC1 rs2642438. As the impact of genetic variants on the levels of drug-metabolizing cytochrome P450 (CYP) enzymes in human hepatocytes has not been thoroughly investigated, this study aims to describe the analysis of metabolic functions for selected phase I and phase II liver enzymes in human hepatocytes. For this purpose, fresh isolated primary hepatocytes were obtained from healthy liver donors (n = 126), and liquid chromatography-mass spectrometry (LC-MS) was performed. For the cohorts, participants were classified into minor homozygotes and nonminor homozygotes (major homozygotes + heterozygotes) for five gene polymorphisms. For phase I liver enzymes, we found a significant difference in the activity of CYP1A2 in human hepatocytes carrying MBOAT7 (p = 0.011) and of CYP2C8 in human hepatocytes carrying PNPLA3 (p = 0.004). It was also observed that the activity of CYP2C9 was significantly lower in human hepatocytes carrying HSD17B13 (p = 0.001) minor homozygous compared to nonminor homozygous. No significant difference in activity of CYP2E1, CYP2C8, CYP2D6, CYP2E1, CYP3A4, ECOD, FMO, MAO, AO, and CES2 and in any of the phase II liver enzymes between human hepatocytes carrying genetic variants for PNPLA3 rs738409, MBOAT7 rs641738, GCKR rs780094, HSD17B13 rs72613567, and MTARC1 rs2642438 were observed. These findings offer a preliminary assessment of the influence of genetic variations on drug-metabolizing cytochrome P450 (CYP) enzymes in healthy human hepatocytes, which may be useful for future drug discovery investigations.

Cutibacterium acnes invades submicron osteocyte lacuno-canalicular networks following implant-associated osteomyelitis.

Cutibacterium acnes, part of normal skin flora, is increasingly recognized as an opportunistic pathogen capable of causing chronic prosthetic joint infections (PJI) associated with total hip and knee arthroplasty. However, there is a paucity of literature examining the pathogenesis of C. acnes during PJI. To study this, we developed an implant-associated osteomyelitis murine model in which 8-10-week-old C57BL6 mice were subjected to transtibial implantation of titanium or stainless-steel L-shaped pins contaminated with C. acnes. Postsurgery, mice were killed on Days 14 and 28 for terminal assessments of (1) bacterial load in bone, implant, and internal organs (heart, spleen, kidney, and liver), (2) bone osteolysis (micro-CT), (3) abscess formation (histology), and (4) systematic electron microscopy (EM). In vitro scanning EM (SEM) confirmed that C. acnes can form biofilms on stainless-steel and titanium implants. In mice, C. acnes could persist for 28 days in the tibia. Also, we observed C. acnes dissemination to internal organs. C. acnes chronic osteomyelitis revealed markedly reduced bone osteolysis and abscess formation compared to Staphylococcus aureus infections. Importantly, transmission EM (TEM) investigation revealed the presence of C. acnes within canaliculi, demonstrating that C. acnes can invade the osteocyte lacuno-canalicular networks (OLCN) within bone. Our preliminary pilot study, for the first time, revealed that the OLCN in bone can be a reservoir for C. acnes and potentially provides a novel mechanism of why C. acnes chronic implant-associated bone infections are difficult to treat.

Polymorphisms Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease Influence the Progression of End-Stage Liver Disease.

BACKGROUND AND AIMS: Chronic liver injury that results in cirrhosis and end-stage liver disease (ESLD) causes more than 1 million deaths annually worldwide. Although the impact of genetic factors on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) has been previously studied, their contribution to the development of ESLD remains largely unexplored. METHODS: We genotyped 6 MASLD-associated polymorphisms in healthy (n = 123), metabolic dysfunction-associated steatohepatitis (MASH) (n = 145), MASLD-associated ESLD (n = 72), and ALD-associated ESLD (n = 57) cohorts and performed multinomial logistic regression to determine the combined contribution of genetic, demographic, and clinical factors to the progression of ESLD. RESULTS: Distinct sets of factors are associated with the progression to ESLD. The PNPLA3 rs738409:G and TM6SF2 rs58542926:T alleles, body mass index (BMI), age, and female sex were positively associated with progression from a healthy state to MASH. The PNPLA3 rs738409:G allele, age, male sex, and having type 2 diabetes mellitus were positively associated, while BMI was negatively associated with progression from MASH to MASLD-associated ESLD. The PNPLA3 rs738409:G and GCKR rs780094:T alleles, age, and male sex were positively associated, while BMI was negatively associated with progression from a healthy state to ALD-associated ESLD. The findings indicate that the PNPLA3 rs738409:G allele increases susceptibility to ESLD regardless of etiology, the TM6SF2 rs58542926:T allele increases susceptibility to MASH, and the GCKR rs780094:T allele increases susceptibility to ALD-associated ESLD. CONCLUSION: The PNPLA3, TM6SF2, and GCKR minor alleles influence the progression of MASLD-associated or ALD-associated ESLD. Genotyping for these variants in MASLD and ALD patients can enhance risk assessment, prompting early interventions to prevent ESLD.

Improving psychotherapeutic medication prescribing in Florida: implementation of the Florida Medicaid Drug Therapy Management Program (MDTMP).

This paper describes a program that was established by Florida Medicaid to improve the quality of prescribing of psychotherapeutic medications. It relates the process used for defining quality medication treatment including the definitions of unusual psychotherapeutic medication indicators (UPMI). It details the results of analysis of FY 2007-2008 pharmacy claims data using these indicators that enabled the Program to identify practices and prescribers that required targeted interventions. The most frequently triggered UPMI for adults involved the use of 2 or more antipsychotics for greater than 60 days; high doses of psychotherapeutic medications was the indicator most frequently triggered for children closely followed by the use of 2 or more antipsychotics for more than 45 days. Prescriptions that triggered UPMI were concentrated in a small number of prescribers. These results led to the Program focusing on these high frequency practices and on the prescribers most associated with them. They also led to the implementation of new quality improvement initiatives like the implementation of a psychiatric telephone consultation line for pediatricians who are treating children with serious emotional disturbances who do not have access to child psychiatrists.

The impact of emotional disturbances on the arrest trajectories of youth as they transition into young adulthood.

This article identifies the arrest trajectories of youth from ages 12 through 24 years old and tests hypotheses derived from Moffitt's developmental taxonomic theory of crime concerning the impact of various emotional disturbances on the specific trajectories of the youth involved. The study uses exclusively administrative data sets and includes a gender and racially diverse sample of 10,360 youth (30.7% females) who were arrested at least once between ages 12 and 24 in the early 2000s. Latent class growth analysis was employed in order to identify distinct arrest trajectories of youth in the sample. Multinomial logistic regression was used to identify diagnostic and other characteristics associated with membership in the specific trajectories predicted by Moffitt's theory. Five trajectory classes were identified, 3 of which were consistent with taxonomic theory including high and classic adolescence limited trajectory classes and a "snared adolescence limited class" described more recently by Moffitt. The distribution of youth among the 5 classes was very different for those with and without emotional disturbances. Youth with emotional disturbances in their late adolescent years were more likely to fall into the high arrest trajectory class and much less likely to fall into the low arrest trajectory class. Compared to youth without an emotional disturbance, youth with psychotic disorders were more than twice as likely to fall into the high as into the low arrest trajectory class. Youth with disruptive behavior disorders were more than twice as likely to fall into the high and intermediate classes as into the low trajectory class. Anxiety and depressive disorders were not associated with significantly greater likelihood of falling into any one of the trajectory classes. Youth in the snared adolescence limited class were more likely than those in the classic adolescence limited class to be male, black versus white and in the foster care enrollment category lending some support to Moffitt's conceptualization of this class as an adolescence limited class composed of youth who are snared by involvement in the criminal justice and or social services systems. Implications of these results for public policy and the study of adolescence are discussed.

Antipsychotic polypharmacy prescribing patterns and costs in the Florida adult and child Medicaid populations.

The rapid growth in the use of antipsychotic medications and their related costs have resulted in states developing programs to measure, monitor, and insure their beneficial relevance to public program populations. One such program developed in the state of Florida has adopted an evidence-based approach to identify prescribers with unusual psychotherapeutic prescription patterns and track their utilization and costs among Florida Medicaid patients. This study reports on the prescriber prescription and cost patterns for adults and children using three measures of unusual antipsychotic prescribing patterns: (1) two antipsychotics for 60 days (2AP60), (2) three antipsychotics for 60 days (3AP60), and (2) two antipsychotics for 90 or more days (2AP90). We find that over the four-year study period there were substantial increases in several aspects of the Florida Medicaid behavioral drug program. Overall, for adults and children, patient participation increased by 29 percent, the number of prescriptions grew by 30 percent, and the number of prescribers that wrote at least one prescription grew 48.5 percent, while Medicaid costs for behavioral drugs increased by 32 percent. But the results are highly skewed. We find that a relatively small number of prescribers account for a disproportionately large share of prescriptions and costs of the unusual antipsychotic prescriptions. In general, the top 350 Medicaid prescribers accounted for more than 70 percent of the unusual antipsychotic prescriptions, and we find that this disparity in unusual prescribing patterns appears to be substantially more pronounced in adults than in children prescribers. For just the top 13 adult and children prescribers, their practice patterns accounted for 11 percent to 21 percent of the unusual prescribing activity and, overall, these 13 top prescribers accounted for 13 percent of the total spent on antipsychotics by the Florida Medicaid program and 9.3 percent of the total expenditure by the state for all drugs. Our findings suggest that a strategy to monitor and ensure patient safety and prescribing patterns that targets a relatively small number of Medicaid providers could have a substantial benefit and prove to be cost effective.

Exposure to antipsychotic medications over a 4-year period among children who initiated antipsychotic treatment before their sixth birthday.

PURPOSE: This study aims the following: (i) to describe the exposure to antipsychotic medications over a 4-year period experienced by a cohort of children who initiated antipsychotic treatment before their sixth birthday; and (ii) to identify variables associated with the risk of antipsychotic exposure. METHODS: Children were identified who initiated an index episode of antipsychotic treatment before their sixth birthday in Florida's fee for service Medicaid program. With the use of claims data, the medication utilization of these children was tracked during the year before and the 4 years following the start of their index episodes (pre-index and four post-index periods). Generalized estimating equations were used to identify variables associated with the risk of additional days of antipsychotic exposure. RESULTS: Five hundred twenty-eight children were included in the cohort. The mean total number of days of exposure was 821.9 (± 431.9), representing 56.3% of all days during the four post-index periods. The mean days of exposure to combinations of antipsychotics and other classes of psychotherapeutic medications were 623.8 ± 447.6 days. Children with primary diagnoses of pervasive developmental disorders and affective disorders were at greater risk of additional days of exposure than children with attention deficit/hyperactivity disorder. Exposure tended to be greater among children with indicators of clinical complexity including the presence of secondary diagnoses and the use of other classes of psychotherapeutic medications in addition to antipsychotics. CONCLUSIONS: Exposure to antipsychotic mediations was extensive. Although these children may have had complex and severe problems, additional research is urgently needed on the benefits and risks of long-term antipsychotic exposure among very young children.

The impact of mental health services on arrests of offenders with a serious mental illness.

This study examines the impact of mental health services on arrests of offenders with a serious mental Illness (SMI) by assessing changes in associations between receipt of outpatient and emergency room/inpatient services and arrests one, two, and three quarters later. A variety of data sets were used for identifying 3,769 offenders who were in the Pinellas County Florida jail between 7/1/2003 and 6/30/ 2004, and 7,755 offenders who were in the Harris County Texas jail between 10/1/2005 and 9/30/2006. Arrests, out-patient and emergency room/inpatient services were assigned to one of 16 ninety-day periods between 7/1/2002 and 6/10/2006 in Pinellas County and one of 12 such periods between 10/1/2004 and 9/15/2007 in Harris County. Generalized estimating equations were used. Covariates were age, gender, race, diagnosis, and homelessness. The results were also adjusted for exposure to arrests. In Pinellas County, outpatient services significantly reduced the risks of arrests 1 quarter later by 17% (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.78-0.87, p < .001), two quarters later by 11% (OR = 0.89, 95% CI: 0.84-0.94, p < .001), and three quarters later by 9% (OR = 0.91, 95% CI: 0.86-0.96, p = .001). In Harris County, these services reduced the risk of arrest 1 quarter later by 5% (OR = 0.95, 95% CI: 0.91-0.99, p = .028), but not two and three quarters later. In Pinellas County, ER/inpatient services increased the risk of arrests by 22% (OR = 1.23, 95% CI: 1.15-1.30, p < .001), 8% (OR = 1.08, 95% CI: 1.02-1.15, p = .010) and 11% (OR = 1.11, 95% CI: 1.02-1.16, p = .001) one, two, and three quarters later. In Harris County, these services increased the risk of arrest only 1 quarter later (OR = 1.16, 95% CI: 1.11-1.22, p < .001). Results suggest that service receipt and its timing may have had some impact on the arrests of adults with a SMI and criminal justice involvement.

Factors related to criminal justice expenditure trajectories for adults with serious mental illness.

BACKGROUND: Criminal careers have been extensively studied in general population sample, but less is known about such patterns among people with major mental illness, and where so, criminal justice expenditure has not been taken into account. AIMS: Our aim was to examine criminal justice system expenditure over time in one Florida county. Our main research question was whether treatment for mental disorders was related to a change in criminal offending and expenditure trajectory. METHODS: We used the Pinellas County (Florida) Criminal Justice Information System to identify individuals under age 65 arrested between July 2003 and June 2004. Archival medical service, social and homeless services data were used to identify individuals with a serious mental illness. A two-step analysis was used to examine the data: first, we identified groups of people with similar patterns of criminal justice expenditures over 4 years (July 2002 to June 2006); second, we evaluated their demographic characteristics, diagnosis and treatment as potential predictors of group membership. RESULTS: Three thousand seven hundred sixty-nine people with serious mental illness were identified in the Pinellas County jail population. Their average length of stay in jail was 151 days and in prison was 48 days. The trajectory analysis identified three groups of individuals with distinct trajectories of criminal justice expenditures: those with low stable, those with initially high but decreasing and those with initially high and sustained or increasing. Mental health treatment, whether acute or sustained, voluntary or mandatory, was associated with membership of the low stable group. CONCLUSION: Review of criminal justice expenditure over time on individuals with major mental disorder may provide important indicators of unmet need for mental health services. Furthermore, it seems probable that improved provision of such services for them could reduce recidivism as well as improving health. Interventions may also be better focused if criminal justice expenditure trajectories are examined; programmes targeting re-offending as well as specific mental health problems may be most effective.

Trends in adult antipsychotic polypharmacy: progress and challenges in Florida's Medicaid program.

We studied trends in antipsychotic polypharmacy over a 4 year period in order to see if a change occurred when a statewide quality improvement program aimed at reducing the practice was implemented. Antipsychotic polypharmacy prevalence rates were calculated for eight 6-month periods for enrollees with schizophrenia and schizoaffective disorder and for those with all other diagnoses. Prevalence increased from 1/2003 to 12/2004 and then declined for 4 successive 6 month periods beginning in the 1/2005-6/05 period when the program began. Piecewise linear regression results for both diagnostic groups confirmed that the change in the likelihood of antipsychotic polypharmacy during the four 6 month periods before program implementation were significantly different than during the four 6 month periods following implementation. While it is impossible to control for the effects of all variables in evaluating the impact of any system wide intervention the data suggest that the program did help to reduce the use of antipsychotic polypharmacy.

Is the risk of antipsychotic polypharmacy discontinuation dependent on the agents used?

This study assesses the risks and benefits of switching from two to one antipsychotic among participants on two non-clozapine oral antipsychotics, and among those on combinations involving either clozapine or an injectable antipsychotic. Ninety adult participants with schizophrenia or schizoaffective disorder were assigned to stay on polypharmacy or to switch to monotherapy. Half of these participants were receiving combinations of non-clozapine oral antipsychotics and half were receiving combinations involving either clozapine or an injectable antipsychotic. Participants were assessed every 60 days for one year. We examined differences in symptom and side effect trajectories as a function of group assignment and time for both medication groups. Participants who switched from two to one non-clozapine oral antipsychotic experienced significant increases in symptoms relative to stay participants. They also saw significant side effect benefits. Switch participants on combinations involving clozapine or an injectable antipsychotic did not differ over time from stay participants on either symptom or side effect measures. It appears that patients on these combinations can be safely switched to monotherapy. While there may be symptom related risks associated with switching patients on combinations of non-clozapine oral antipsychotics, there are significant health related benefits. Clozapine or injectable antipsychotic monotherapy are recommended options.

The risks and benefits of switching patients with schizophrenia or schizoaffective disorder from two to one antipsychotic medication: a randomized controlled trial.

BACKGROUND: Despite little evidence to support its use and practice guidelines discouraging the practice, antipsychotic polypharmacy is widely prevalent in schizophrenia. This randomized controlled trial studied the effects of switching patients stable on two antipsychotic medications to one antipsychotic medication. METHOD: 104 adult outpatients with schizophrenia from 7 community mental health centers clinically stable on concurrent treatment with 2 antipsychotics were randomly assigned to stay on polypharmacy or to switch to antipsychotic monotherapy. Participants were followed for 1-year with assessments of symptoms and side effects occurring every 60days (7 total assessments). We examined differences in time trajectories in symptoms (PANSS, CGI) and side effects (EPS, metabolic, other) as a function of group assignment (switch vs. stay) and time, using intention-to-treat analysis. RESULTS: Participants who switched to antipsychotic monotherapy experienced greater increases in symptoms than stay patients. These differences emerged in the second 6months of the trial. All-cause discontinuation rates over the 1-year trial were higher in the switch-to-monotherapy group than in the stay-on-polypharmacy group (42% vs. 13%; p<0.01). There were no differences in change over time in any of the side effect measures, except that stay patients experienced a greater decrease in Simpson Angus total scores than switch patients. CONCLUSION: Clinicians should be cautious in switching patients with chronic schizophrenia who are stable on 2 antipsychotics to one antipsychotic. Given the challenges in discontinuing antipsychotic polypharmacy, adequate trials of evidence-based treatments such as clozapine and long-acting injectable antipsychotics should be undertaken in inadequately responsive schizophrenia patients before moving to antipsychotic polypharmacy.

Impact of the Florida Medicaid prior-authorization program on use of antipsychotics by children under age six.

OBJECTIVE: This study assessed the impact of a prior-authorization process on the use of antipsychotic medications by children under six years old in Florida's fee-for-service Medicaid program. METHODS: Child psychiatrists reviewed requests for antipsychotic treatment (N=1,424) using forms and criteria created by a panel of Florida-based experts. Data on the characteristics of the children and clinicians involved were organized into 11 consecutive quarters beginning in July 2008. Multivariate generalized estimating equations were used to examine the association between each study variable and changes in the odds of submission of a new request over time. RESULTS: Prior-authorization requests declined from 124 in the first quarter to 81 in the last quarter. Compared with applications from child psychiatrists, the odds of applications being submitted by adult psychiatrists, neurologists, and pediatricians increased over time. CONCLUSIONS: Although applications declined, the diminished role of child psychiatry specialists raises questions about the impact of the program on the quality of care provided.

Gender differences and risk of arrest among offenders with serious mental illness.

Despite the increasing number of men and women with serious mental illness (SMI) incarcerated in America's jails, little research exists on the role gender may play in arrest among persons with SMI. This study examined correlates of arrests among offenders with SMI, specifically the role of gender. County criminal justice records, as well as county and statewide social service archival databases, were used to identify jail inmates with SMI in a large urban county in Florida. Of the 3,769 inmates identified, 41% were female. This study identified three distinct classes of male and female offenders within which persons had similar trajectories of arrests over the 4-year study period representing those with minimal, low, and high arrest rates. Findings suggest some important differences between women and men in risk factors for re-arrests. Attention to these factors may improve the ability to prevent future recidivism among men and women with SMI.

Association of involuntary psychiatric examination with probability of arrest of people with serious mental illness.

OBJECTIVE: This study examined the association between the occurrence of an involuntary psychiatric examination under Florida civil commitment law and the probability of arrest during the next quarter. METHODS: County criminal justice records and several statewide and local health and social service data sets were used to identify inmates with a serious mental illness who spent at least one day in the Pinellas County jail between July 1, 2003, and June 30, 2004. These same data sets were combined with statewide arrest and prison records to identify the criminal justice and health and social services histories of these individuals from July 1, 2002, to June 10, 2006, with the four-year period divided into 16 periods of 90 days. The main analysis used individual fixed-effects models to examine the relationship between involuntary examinations and subsequent probability of arrest. RESULTS: There were 3,728 inmates with serious mental illness in the sample, with 40% (N = 1,485) having at least one involuntary examination during the four-year period. Individuals who experienced an involuntary examination during the four years were arrested in 34% (N = 1,038) of the quarters after an examination and in 27% (N = 3,786) of the quarters not preceded by an involuntary examination. Individual fixed-effects models found a significant positive relationship between the receipt of an involuntary examination in one period and the likelihood of arrests, felony arrests, and misdemeanor arrests in the next period. CONCLUSIONS: Involuntary psychiatric examinations were associated with increased risk of arrest. Thus an involuntary examination was a significant signal that individuals with serious mental illness were at risk for criminal behavior and arrest.

Early diagnoses and psychotherapeutic medication treatment experiences of a cohort of children under 6 years old who received antipsychotic treatment in Florida's Medicaid program.

OBJECTIVE: To describe the diagnostic characteristics and psychotherapeutic medication experiences of a cohort of children who received antipsychotic treatment before their sixth birthday. METHODS: Children enrolled in Florida's Medicaid program were identified as having initiated an index episode of antipsychotic treatment before their sixth birthday. The characteristics of these children were compared to nonrecipients who were less than 6 years old on January 1, 2004. An index episode is described as the filling of at least two consecutive antipsychotic prescriptions with a gap no greater than 15 days between the last day supplied of the first prescription and the fill date of the second prescription. We describe the diagnoses and psychotherapeutic medication experiences of these children during the 365 days before the start of their index episodes (preindex periods) and during the 365 days immediately after the start of their index episodes (index periods). RESULTS: Five hundred twenty-eight recipients were identified. Recipients were more likely than nonrecipients to be male, to be older, and to have a supplemental security income enrollment status. Recipients were exposed to psychotherapeutic medications at very early ages. Four hundred thirty-nine (83%) had already been treated with some psychotherapeutic medication during their preindex periods. Of these children, 303 (69%) filled at least one prescription for an antipsychotic medication. Index antipsychotic episodes were often lengthy. Mean ± standard deviation and median episode lengths were 266.9 ± 286.8 and 174 days, respectively. During the index periods half of the children were found to have attention-deficit/hyperactivity disorder and 18% had disruptive behavior disorders. Treatment during these periods included other classes of psychotherapeutic medications for 73% of children. Nearly 30% (29.6%) received two or more classes of medications in addition to antipsychotics. CONCLUSIONS: We found a large group of very young children who were persistently treated with antipsychotic medications. This early and extensive exposure is a cause for concern.

Risperidone long-acting therapy prescribing patterns and their impact on early discontinuation of treatment in a large Medicaid population.

OBJECTIVE: Medicaid claims were examined to determine whether utilization of risperidone long-acting therapy (LAT) was consistent with manufacturer's prescribing information recommendations and what factors were associated with early discontinuation. METHOD: Florida Medicaid claims between July 1, 2003, and June 30, 2007, were used. Recipient demographics and diagnoses, provision of oral antipsychotic supplementation during the first 21 days, number of injections received, medication possession ratio, and augmentation/polypharmacy after the first 21 days were assessed. Logistic regression was used to identify factors associated with early discontinuation of risperidone LAT. RESULTS: There were 3,364 individuals who received 4,546 episodes of risperidone LAT. Most recipients were between 18 and 64 years and had schizophrenia or schizoaffective disorder. Median episode length was 106 days. Median number of injections was 5. Supplementation with oral antipsychotic during the first 21 days was provided in 48% of episodes. Mean dosages were 25 mg or less for 28% of episodes and greater than 75 mg for 7% of episodes. Augmentation/polypharmacy after the first 21 days occurred in 43% of episodes. Early risperidone LAT discontinuation was associated with absence of oral supplementation during the first 21 days (P < .001), low (P = .045) or high (P < .001) initial doses of risperidone LAT, prior inpatient treatment (P < .001), having a substance use disorder (P = .001), and being male (P = .036). CONCLUSIONS: Prescribing practices for risperidone LAT were compared with the recommended protocol. Risperidone LAT was typically used with recommended age and diagnostic groups. However, important discrepancies were identified that could have reduced perceived effectiveness and tolerability of risperidone LAT. Early discontinuation was less likely when the recommendations in the manufacturer's prescribing information regarding dosage and supplementation with oral antipsychotics were followed.

Antipsychotic polypharmacy in the treatment of children and adolescents in the fee-for-service component of a large state Medicaid program.

OBJECTIVES: The aims of this study were to quantify and describe antipsychotic polypharmacy use among patients aged 6 to 12 years (children) and 13 to 17 years (adolescents) and to identify the characteristics of polypharmacy recipients. METHODS: Data from patients enrolled in Florida's Medicaid fee-for-service program and receiving treatment with an antipsychotic were included. Antipsychotic polypharmacy was defined as the receipt of > or = 2 antipsychotic medications concurrently for >60 days, with no gaps >15 days in polypharmacy treatment. The prevalence of antipsychotic polypharmacy, durations of treatment episodes, times to antipsychotic polypharmacy after initiation of antipsychotic monotherapy, and rates of antipsychotic combination use were calculated for the period between July 2002 and June 2007. RESULTS: During the 5-year period, 12,764 children and 10,419 adolescents received antipsychotic treatment. The proportions of patients who were male (73% and 63%) and whose race was indicated as "other" (31% and 14%) were significantly greater in children than in adolescents, respectively (both, P < 0.001). Seven percent of the children and 8% of the adolescents were prescribed antipsychotic polypharmacy (P = 0.001). Mean (SD) durations of polypharmacy episodes were 170.0 (139.0) days in children and 185.5 (175.9) days in adolescents (P = 0.010). Times to initiation of polypharmacy were 505.8 (440.5) days in children and 384.9 (424.3) days in adolescents (P < 0.001). Adolescents (odds ratio [OR] = 1.16; 95% CI, 1.04-1.29) were more likely than children to be polypharmacy recipients, as were those with psychotic disorders (OR = 1.47; 95% CI, 1.20-1.81) compared with those with bipolar I disorder. Patients whose race was indicated as "other" were more likely than patients of white race to receive polypharmacy (OR = 1.18; 95% CI, 1.04-1.34; P < 0.001); other ethnic/racial groups did not differ significantly. The most common specific antipsychotic combinations prescribed in children and adolescents were aripiprazole/quetiapine (23% and 17%, respectively), risperidone/quetiapine (18% and 15%), aripiprazole/risperidone (17% and 11%), risperidone/olanzapine (5% and 6%), and quetiapine/olanzapine (4% and 7%). CONCLUSIONS: The prevalence and duration of Antipsychotic polypharmacy among antipsychotic recipients in this Medicaid fee-for-service population were noteworthy. Research on the risks and benefits of the practice in the pediatric population is needed.

Public expenditures related to the criminal justice system and to services for arrestees with a serious mental illness.

OBJECTIVE: The study identified expenditures related to criminal justice, health, mental health, and social welfare services over a four-year period for arrestees with serious mental illnesses in a large Florida county and characteristics of subgroups. METHODS: Multiple data sets were used to identify 3,769 persons arrested in a one-year period who had serious mental illnesses. Multiple regression with all variables mutually adjusted was used to explore associations with a log of aggregate criminal justice, health, mental health, and social welfare expenditures. RESULTS: Aggregate expenditures were $94,957,465, with a median per person of $15,134. Individuals with the highest expenditures were at least 40 years old with a psychotic disorder, an involuntary psychiatric examination, and more arrests and mental health contacts. Medicaid enrollees had higher expenditures than nonenrollees overall but lower criminal justice expenditures. CONCLUSIONS: Identifying characteristics of subgroups with higher expenditures may assist policy makers and providers in designing appropriate criminal justice and treatment responses.

Short-term impact of preferred drug list changes on health care use and Medicaid costs: injectable risperidone.

OBJECTIVE: This study assessed short-term effects of the removal of injectable risperidone long-acting therapy from the Florida Medicaid preferred drug list (PDL) in April 2006. METHODS: A difference-in-difference approach was used to contrast changes (60 days pre and post) in health care utilization and costs of Medicaid recipients who were receiving risperidone long-acting therapy when the policy was changed (N=247) and of a matched sample who received risperidone long-acting therapy in April 2005 (non-PDL, N=247). RESULTS: The policy change was associated with increased acute care events. Whereas acute care events declined for the non-PDL group, involuntary commitments and total acute care events increased for the PDL group, as did expenditures for crisis-related events. Medicaid pharmacy costs fell for both groups, but total expenditures did not decline significantly for the PDL group. CONCLUSIONS: The PDL restriction was associated with increased acute care events and did not reduce short-term Medicaid program expenditures.