Treatment of schizophrenia with depot preparations of fluphenazine, haloperidol, and risperidone among inpatients at state-operated psychiatric facilities.

BACKGROUND: This study aimed to characterize the inpatient utilization of depot antipsychotics. METHOD: The characteristics of adults with schizophrenia or schizoaffective disorder, hospitalized for at least 28 days, and who were prescribed depot antipsychotics were examined from 2004 to 2006 using a database from a large state-operated psychiatric hospital system. Demographic and clinical characteristics of patients receiving depot fluphenazine or haloperidol were compared to those prescribed depot risperidone. RESULTS: We identified 2210 unique patients who initiated treatment with a depot antipsychotic (after receiving oral antipsychotics). Of these, 1484 (67.1%) received depot fluphenazine or haloperidol, and 726 (32.9%) received risperidone as their initial depot antipsychotic. Patients who received depot risperidone did not differ from those receiving depot fluphenazine or haloperidol with regard to demographics, diagnosis of schizoaffective disorder, number of comorbid psychiatric or medical diagnoses, or diagnosis of substance abuse. Patients started on depot risperidone during the observation period had a longer length of stay prior to initiation of depot than those started on depot fluphenazine or haloperidol (583 days vs. 237 days, t=5.489, p<.001). Patients who started on depot risperidone were less likely to be discharged on that medication than were patients who started on depot fluphenazine or haloperidol (odds ratio from Cox regression model=0.846 [95% CI 0.745-0.960]). CONCLUSIONS: Patients initiated on depot risperidone had a longer length of stay prior to their first injection and were less likely to be discharged on that medication compared to patients initiated on depot fluphenazine or haloperidol, possibly indicating that patients initiating depot risperidone had a more severe or treatment-resistant course of illness and/or that there were reimbursement barriers for the outpatient utilization of depot risperidone, or that efficacy differences exist between the depot antipsychotics at the doses used in this population.

How dosing of ziprasidone in a state hospital system differs from product labeling.

BACKGROUND: The purpose of this article is to review the utilization and dosing of ziprasidone in a state hospital system and to compare the dosing to dosing recommendations contained in product labeling that suggest a starting dose of 40 mg/day and a target dose range of 40 to 160 mg/day for schizophrenia. METHOD: Dosing of ziprasidone was examined from the time when it was first marketed in 2001 up to and including calendar year 2006 using a database that contains patient information and drug prescription information for every inpatient within the adult civil facilities of the New York State psychiatric hospital system operated by the New York State Office of Mental Health. Supporting evidence for a therapeutic dose response for ziprasidone was examined by conducting a PubMed search for the period January 1, 1990, to June 1, 2008, identifying English-language articles related to ziprasidone dose in schizophrenia using the search terms ziprasidone, dose, and schizophrenia. RESULTS: Although the highest efficacious dose of ziprasidone recommended in the manufacturer's product label is 160 mg/day, the mean dose of ziprasidone prescribed among patients hospitalized in New York State in calendar year 2006 and receiving antipsychotic medication (N = 7154) was 179 mg/day (N = 709), with 51.6% receiving doses in excess of 160 mg/day (N = 366). Patients discharged on treatment with ziprasidone (N = 189) received a mean dose of 206 mg/day. Patients with schizophrenia with a history of prior state hospital admission were more likely to receive doses greater than 160 mg/day. Clinicians in hospitals with the highest prescribing rates for ziprasidone were more likely to prescribe ziprasidone in excess of 160 mg/day. The initial dose on the first day for new starts on treatment with ziprasidone was 91 mg/day (N = 112). Published anecdotal reports describe the use of ziprasidone in excess of 160 mg/day and up to 640 mg/day among patients not responding to lower doses, but, currently, there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy. CONCLUSIONS: Dosing of ziprasidone in a large state hospital system is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of ziprasidone in excess of 160 mg/day, controlled clinical trials are needed to determine if these higher doses are more effective.

"Stat" medication administration predicts hospital discharge.

OBJECTIVE: This study describes the use of "stat" medications for inpatients in a large state psychiatric hospital system, and examines the relationship between receipt of a "stat" for agitation and subsequent hospital discharge. METHODS: Use of "stat" medications in 2005 was retrospectively determined using a database that contains diagnosis and prescription information from 17 state-run adult civil facilities. A logistic regression model explored the relationship between receipt of a "stat" order for intramuscular preparations of either antipsychotics or lorazepam within the first 30 days of hospitalization and likelihood of hospital discharge by 6 months. RESULTS: Among 7,202 patients who received antipsychotic medication in 2005, 3,240 (45%) also received a "stat" psychotropic medication during that year. Among 40,651 stat orders, 19,142 (47%) were for intramuscular antipsychotics or lorazepam presumably given for the treatment of agitation. Among 1,673 patients admitted in the first 6 months of 2005, 415 (25%) received at least one such "agitation stat." The percent discharged at six months among "agitation stat" receivers was 39%, compared to 69% among those who did not receive an "agitation stat" (chi-square = 115, df = 1, P < .001). Regression analysis showed that receiving an "agitation stat" in the first 30 days of hospitalization was associated with a 37% lower likelihood of being discharged by 6 months after admission (odds ratio .63, 95% CI: .46-.86). CONCLUSIONS: "Stat" medications are commonly used. The use of "agitation stat" medications can be used as a proxy for clinical stability and may prove to be a useful outcome measure for future pharmacoepidemiologic studies of comparative medication effectiveness.

Incidence, prevalence, and surveillance for diabetes in New York State psychiatric hospitals, 1997-2004.

OBJECTIVE: The purpose of the study was to describe the incidence of newly treated diabetes mellitus, the prevalence of identified cases, and surveillance for new cases between 1997 and 2004 among inpatients in a large state psychiatric hospital system. METHODS: Prevalence was determined by ascertaining the number of individuals who received antidiabetic medication or had a diagnosis of diabetes mellitus for each calendar year in inpatient facilities operated by the New York State Office of Mental Health. Yearly incidence was calculated by identifying unique patients who received new prescriptions of antidiabetic medication among patients with no known history of receiving such medication and no recorded diagnosis of diabetes mellitus. Surveillance for abnormal plasma glucose levels was measured by calculating the number of plasma glucose tests completed per 100 patient-days among patients without diabetes mellitus. RESULTS: Prevalence of identified cases of diabetes increased from 6.9 percent of 10,091 patients in 1997 to 14.5 percent of 7,420 patients in 2004 (risk ratio [RR] = 2.11, 95 percent confidence interval [CI] = 1.93-2.31). Incidence of newly treated diabetes increased from .9 percent in 1997 to 1.8 percent in 2004 (RR = 2.03, CI = 1.51-2.73). The increase in incidence and prevalence was only partially explained by the increase in surveillance for new cases, which increased from 1.23 plasma glucose tests per 100 patient-days in 1997 to 1.80 in 2002 (RR = 1.46, CI = 1.43-1.50). CONCLUSIONS: The doubling of the treated incidence rate and the rise in prevalence of identified cases of diabetes among psychiatric inpatients mirrors the rise observed in the general population but with higher absolute rates.

Dosing of quetiapine in schizophrenia: how clinical practice differs from registration studies.

BACKGROUND: A substantial number of patients with psychosis receive quetiapine in amounts that are greater than what is recommended in the product labeling approved by drug regulatory agencies. The purpose of this article is to review the past and present dosing patterns of quetiapine for the treatment of schizophrenia. METHOD: A PubMed search for the period January 1, 1990, to July 1, 2005, was conducted to identify English-language articles related to quetiapine dose in schizophrenia using the search terms quetiapine, dose, and schizophrenia. Trends in dosing of quetiapine in a large, state-operated psychiatric hospital system and the anecdotal evidence describing the use of quetiapine in excess of 800 mg/day were also reviewed. RESULTS: The registration studies of quetiapine suggest a target dose range of 300 to 500 mg/day for schizophrenia. In contrast, among inpatients hospitalized in New York State in the period of April 1, 2004, to June 30, 2004, the mean dose of quetiapine prescribed was 620 mg/day, with 33.6% receiving doses in excess of 750 mg/day. Patients with nonwhite ethnicity, length of stay of at least 1 year, or history of prior state hospital admission were more likely to receive doses greater than 750 mg/day. Patients receiving quetiapine as antipsychotic monotherapy or in combination with other antipsychotics were equally likely to receive doses greater than 750 mg/day. Published anecdotal reports describe the use of quetiapine in excess of 800 mg/day and up to 2400 mg/day among patients not responding to lower doses, but currently there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy. CONCLUSIONS: Dosing of quetiapine in clinical practice is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of quetiapine in excess of 800 mg/day, double-blind randomized clinical trials are needed.

Relationship between antipsychotic medication treatment and new cases of diabetes among psychiatric inpatients.

OBJECTIVE: This study examined data on patients with serious and persistent mental illness in a large state hospital system to determine whether patients who took second-generation antipsychotics were more likely to develop diabetes mellitus than patients who took first-generation antipsychotics. METHODS: A case-control study design was used. A new prescription of an antidiabetic medication was used to identify new cases of diabetes mellitus. Odds ratios were calculated for exposure to second-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, and multiple second-generation antipsychotics) compared with exposure to first-generation antipsychotics. Cases and controls were identified by using a database that contained drug prescription information from the inpatient facilities that were operated by the New York State Office of Mental Health. Data from January 1, 2000, to December 31, 2002, were examined. Among 13,611 unique patients who received antipsychotics, 8,461 met entry criteria of being hospitalized for at least 60 days and not having an antidiabetic medication prescribed in the past. A total of 181 of these inpatients received prescriptions for an antidiabetic medication at least 30 days after their admission. Eight controls (N=1,448) for each case (N=181) were matched by calendar year, length of observation period, race, age group, and diagnosis, giving a total sample of 1,629 patients. RESULTS: Statistically significant elevations in risk were seen among patients who received more than one second-generation antipsychotic or clozapine or quetiapine, compared with patients who received first-generation antipsychotics alone. Although not statistically significant, odds ratios for olanzapine and risperidone were also elevated. Conditional logistic regression adjusting for gender and age did not change the results. CONCLUSIONS: Exposure to multiple second-generation antipsychotics or clozapine or quetiapine significantly increased the risk of treatment-emergent diabetes mellitus.

Efficacy and effectiveness of first- and second-generation antipsychotics in schizophrenia.

While efficacy as a concept is concerned with whether a treatment works under ideal conditions, effectiveness is concerned with whether a treatment works under the conditions of routine care. Large-scale clinical, pharmacy, and administrative databases can provide naturalistic data for effectiveness studies when appropriate methodology is employed. The Nathan Kline Institute Integrated Research Database includes patient-specific admission, demographic, diagnostic, medication, and discharge information from hospitals operated by the New York State Office of Mental Health. This database was used to study the effectiveness of first- versus second-generation antipsychotics in the treatment of schizophrenia and schizoaffective disorder. Switching off the index medication regimen prior to discharge (negative outcome) was our principal outcome of interest. We concluded that, as a class, second-generation antipsychotics were less likely than first-generation agents to be associated with premature discontinuation of an antipsychotic regimen, both when used as the initial medication regimen following hospitalization and as the second regimen following a prior medication switch.

Relationship of atypical antipsychotics with development of diabetes mellitus.

OBJECTIVE: To review the pharmacoepidemiologic evidence for the link between exposure to atypical antipsychotics and the development of diabetes mellitus. DATA SOURCES: A MEDLINE search (1990-March 2003) was conducted. STUDY SELECTION AND DATA EXTRACTION: The search was limited to articles that described findings from analyses of large databases and used the words diabetes or hyperglycemia, and antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone or aripiprazole in the title or abstract. The odds ratio or relative risk, together with their corresponding confidence interval, was extracted. DATA SYNTHESIS: Results are conflicting, and this variability may be due to the different populations studied, different study designs, and the possibility of publication bias related to funding by the pharmaceutical industry. Nevertheless, an increased risk for diabetes mellitus appears to be present for patients receiving atypical antipsychotics. However, differential risk among the atypical antipsychotics is difficult to ascertain. CONCLUSIONS: Clinicians are urged to manage risk by regularly monitoring all patients receiving atypical antipsychotics for the emergence of diabetes mellitus. Future studies should carefully control for confounding variables such as age, diagnosis, change in weight, activity level, family history, and ethnicity.

Antipsychotic medication coprescribing in a large state hospital system.

PURPOSE: To systematically characterize antipsychotic medication coprescribing ('polypharmacy') in a large state hospital system. METHODS: All antipsychotic prescriptions written for all adult in-patients (N = 8212) in New York state-run civil facilities for the year 1999 were identified using the Integrated Research Database (IRDB) created by the Information Systems Division of the Nathan Kline Institute for Psychiatric Research. Antipsychotics were considered to be intentionally coprescribed only when both were prescribed for an overlapping period of 28 days. RESULTS: Coprescribing of typical, atypical, and depot antipsychotics comprised 31% of antipsychotic prescribing episodes. Medications were usually coprescribed with medications from outside their own antipsychotic class. Patient factors, such as age, diagnosis, and history of prior hospitalization, affected coprescribing rates (p < 0.001 for all indicated variables). Atypical antipsychotic medications were less likely to be given with another antipsychotic than were oral or depot typical medications. CONCLUSIONS: Coprescribing of antipsychotic drugs is a common practice in the New York State hospital system. The analysis of large clinical databases can yield valuable information about the kinds of complex pharmacotherapy regimens actually utilized in the treatment of the most severely ill patients.