Variations in prescribing practices for novel antipsychotic medications among Veterans Affairs hospitals.

This study examined prescribing practices for antipsychotic medications at 13 Veterans Affairs (VA) medical centers and whether patients' sociodemographic characteristics were associated with receiving novel agents. Automated pharmacy data were used to identify 599 patients who had been diagnosed as having schizophrenia and who had received a prescription for an antipsychotic medication after their last discharge from a VA medical center in 1997. Novel antipsychotics were found to have been prescribed for almost half of the patients (47 percent). In logistic regression analysis, significant variations in prescription of novel agents were found among the facilities and among ethnic groups. The results of this study suggest that prescribing practices are influenced by both facility and patient characteristics.

Predictors of patient entry into alcohol treatment after initial diagnosis.

To improve the quality of care for alcohol-related disorders, key transitions in the continuum of care, including treatment entry, must be fully understood. The purpose of this study was to investigate identifiable predictors of patient entry into a substance-use treatment program following the initial diagnosis of an alcohol-related disorder on a medical or surgical inpatient unit. An administrative computerized database was used to identify the sample for this study. Inpatient and outpatient records were obtained from the Little Rock VAMC/DHCP. Predictors of patient entry into treatment within six months of the initial diagnosis of an alcohol related disorder included age younger than than 60 (odds ratio [OR] = 4.6), not married (OR = 1.7), primary diagnosis of an alcohol-related disorder (OR = 7.7), diagnosis of a comorbid drug (OR = 4.3) or psychiatric disorder (OR = 3.6), diagnosis by a medical as opposed to a surgical specialty (OR = 6.0), and African American (OR = 1.7).

Quality Enhancement Research Initiative in Mental Health.

The Veterans Administration (VA) recently introduced its Quality Enhancement Research Initiative (QUERI) to facilitate the translation of best practices into usual clinical care. The Mental Health QUERI (MHQ) was charged with developing strategic plans for major depressive disorder (MDD) and schizophrenia. Twenty percent or more of VA service users are affected by 1 of these 2 disorders, disorders that often have a devastating impact on affected individuals. Despite the increasing availability of efficacious treatments for each disorder, substantial gaps remain between best practices and routine care. In this context, the MHQ identified steps critical to the success of a sustained process of rapid-cycle health care improvement for MDD and schizophrenia, including research initiatives to close gaps in knowledge of best treatment practices, demonstration projects to close gaps in practice and to expand understanding of effective strategies for implementing clinical guidelines, targeted enhancements of the VA information system, and research and dissemination initiatives to increase the availability of resources to support the accelerated incorporation of best practices into routine care. This article presents an overview of the elements in the initial MHQ strategic plans and the rationale behind them.

Performance measurement for schizophrenia: adherence to guidelines for antipsychotic dose.

OBJECTIVE: This report describes the development, application, and exploratory evaluation of a clinical performance measure based on recently published schizophrenia guidelines for antipsychotic dose. DESIGN, SETTING, PARTICIPANTS: The performance measure, which assesses adherence to antipsychotic dose recommendations for acute schizophrenia treatment, was calculated at hospital discharge for 116 patients with schizophrenia who had participated in a 6-month outcomes study. MAIN OUTCOME MEASURE: The Brief Psychiatric Rating Scale (BPRS) was used to assess symptom severity at 6-month followup. RESULTS: At discharge, almost one-half of the patients were prescribed doses outside the recommended range. For the entire sample, linear regression models showed that the performance measure variable was not significantly associated with followup symptom severity (BPRS total scores). However, a significant association was observed for patients prescribed oral antipsychotics only (n = 69). Patients prescribed recommended doses had lower adjusted mean BPRS totals than patients prescribed doses either greater than (P < 0.05) or less than (P < 0.05) recommended. CONCLUSIONS: Our findings suggest that the antipsychotic dose performance measure may be useful for monitoring quality. It assesses a modifiable aspect of care for which clinical improvement is needed, and such improvement is likely to improve patient outcomes. Future research is needed to confirm our findings and to develop and test interventions to improve the quality of care for schizophrenia that incorporate this clinical performance measure.

The feasibility of using automated data to assess guideline-concordant care for schizophrenia.

This study examines the feasibility of using automated computer data versus written medical record data to identify patients receiving guideline concordant treatment for schizophrenia. Central elements of care derived from published practice guidelines for schizophrenia were examined for a convenience sample of 28 patients who received acute inpatient treatment. The results showed that automated data were superior to medical record data for identifying some elements of guideline-concordant treatment. Not only were the elements of care examined in this study clinically significant and within the current capabilities of the existing computer information system, but they are also likely related to patient outcomes. Implications for clinical care, future research, and health care quality improvement efforts are discussed.

Quality of public sector care for schizophrenia in Arkansas.

OBJECTIVE: Using process-of-care indicators, we examined the quality of care provided to 139 individuals receiving treatment for schizophrenia in public sector systems. METHODS: Longitudinal data on services use and medication management were abstracted from medical records. Medication adherence data were obtained by self- and informant reports. RESULTS: Overall, 39% of participants had less than monthly contact with community-based service (CBS) providers. When participants in day treatment or partial hospitalization programs were excluded, less than monthly CBS contact increased to 70%. Of participants, 40%-60% were prescribed medications outside guideline-recommended dose ranges. Up to half of participants reported taking half or less of prescribed antipsychotics. The adverse impact on patient outcomes of these practice patterns is well established. CONCLUSIONS: Public sector organizations face powerful challenges to the behavioral changes needed to sustain best practice care. Overcoming these challenges to assure high-quality care for schizophrenia will require tremendous creativity and commitment.

Geographic market areas for psychiatric and medical outpatient treatment.

The research objective was to measure the variation in the size of a facility's market areas across different diagnostic categories. Specifically, the market area radii for outpatient psychiatric services are compared to the radii for outpatient medical services. Data were collected from the outpatient clinics of the Little Rock Veterans Administration Medical Center. Visits were categorized into 100 diagnostic groups. The market radius for each diagnostic group was defined as the 75th quartile of the distribution of distances traveled. All psychiatric diagnostic groups had significantly (p < 0.05) smaller market area radii than the overall sample radius. The average market area radius across psychiatric illnesses was 62.2 miles, which was significantly (p < 0.05) smaller than the average radius across medical illnesses (90.6 miles). Results suggest that rural patients with mental illness may not receive adequate care and that specialized outreach programs may need to be developed to better serve this population.

Diagnosis and management of substance use disorders among inpatients with schizophrenia.

OBJECTIVE: The study examined the extent of clinical recognition of comorbid substance use disorders and the clinical management of these disorders among inpatients hospitalized for an acute exacerbation of schizophrenia. METHODS: Medical records of 42 inpatients who met research diagnostic criteria for both schizophrenia and a current substance use disorder were reviewed for information about admission evaluation, inpatient management, discharge diagnosis, and disposition. RESULTS: Alcohol use disorders were the most frequent co-occurring substance-related diagnoses, found for 86 percent of the dually diagnosed inpatients. Twenty-four patients (57 percent) did not receive a diagnosis of a substance-related disorder at admission, and 19 (45 percent) did not receive a substance-related diagnosis at discharge. Referral to inpatient or outpatient substance abuse treatment was documented for a minority of subjects. CONCLUSION: The results suggest that improvements are needed in the process of clinical care for inpatients with schizophrenia who have co-occurring substance-related disorders. They highlight a need for education of health care providers and continuous quality improvement in this area.

Effectiveness of care and improvement of quality of life in patients with panic disorder.

To investigate how practice guidelines or recommendations can be applied in the assessment of quality of care, 72 subjects beginning specialty treatment for panic disorder were enrolled. The Panic Outcomes Module assessed symptoms, health status, and treatment at baseline and after 8 weeks. Using published guidelines, the authors developed specific criteria to rate whether subjects' reports reflected appropriate treatment, including antipanic medication or three or more subsequent visits that involved antipanic behavioral therapy elements. Sixty-nine subjects (96%) completed the Panic Outcomes Module at both baseline and follow-up. Improvement in symptoms and health status was not different between subjects receiving appropriate and inappropriate care.

Validation of the Panic Outcomes Module.

This article discusses the validation of a module designed to evaluate the outcomes of clinical care for panic disorder. The research utilized a longitudinal design to examine cross-sectional relationships and change over time within and between subjects. Baseline, follow-up, and test-retest data were collected on 73 patients. The initial field test indicates that the Panic Outcomes Module measures outcomes and case-mix characteristics with acceptable levels of measurement error for group data. The module's measure of change in panic severity demonstrated encouraging agreement with the structured interviewer's judgement of change. This module, completed in approximately 20 minutes, is short enough to incorporate into outpatient mental health settings. We recommend that providers and administrators interested in monitoring the outcomes of specialty care for panic disorder seek assistance from health services researchers to use the Panic outcomes module. Further research is needed to validate this module for use in primary care populations.

An instrument for measurement of outcomes of care for schizophrenia. Issues in development and implementation.

To advance effectiveness research in mental health, we need common, standardized, validated instruments that can be used easily in routine practice settings. The Schizophrenia Outcomes Module is a relatively brief, comprehensive instrument for monitoring and assessing the outcomes of treatment for schizophrenia in clinical care settings. The module was developed with the guidance of a multiinstitutional, multidisciplinary expert panel; the clinical and theoretical considerations that framed the expert panel's deliberations and determined the module's content and characteristics are described. Initial field testing of the instrument involved longitudinal observation of 100 individuals with schizophrenia over a 6-month period. To our knowledge, it is the only brief and easily administered instrument that encompasses the four major outcome domains defined by the National Institute of Mental Health's Plan for Research on the Severely Mentally Ill. As such, it is a promising tool for effectiveness research in schizophrenia.

Awareness of illness in schizophrenia and outpatient treatment adherence.

We present a brief measure of awareness of illness in schizophrenia and test whether awareness is related to perceived need for and adherence to outpatient psychiatric treatment. A prospective design assessed treatment adherence, awareness of the signs and symptoms of schizophrenia, symptoms, neurocognitive status, and substance abuse at baseline and 6-month follow-up in 89 persons with schizophrenia. Results indicate that persons with greater awareness perceived greater need for outpatient treatment and evidenced better adherence to outpatient treatment when adherence and awareness were measured concurrently. Awareness was not related to adherence at 6-month follow-up. In addition, neurocognitive impairment was associated with lower overall adherence to treatment when reported by collaterals at baseline and 6-month follow-up. Neurocognitive impairment was, however, associated with higher self-reported adherence to medication, which suggests that neurocognitive status may bias adherence reporting in persons with schizophrenia.

Cost-effectiveness of clozapine monitoring after the first 6 months.

BACKGROUND: Clozapine is effective in treating patients with schizophrenia who do not respond to conventional neuroleptic drugs. The drug is unique in that it is available only with a US Food and Drug Administration-mandated system for weekly monitoring of patients' white blood cell counts. No study has been conducted to evaluate the cost-effectiveness of this mandatory monitoring system. METHODS: A benchmark case was established by utilizing cumulative incidence rates of agranulocytosis from a recent study with a large sample of clozapine-treated patients. We assumed a 20% mortality among patients with agranulocytosis, $30.61 in monitoring costs each week, and 14.4 years of remaining life expectancy after detection of agranulocytosis. Based on these bench-mark assumptions, cost-effectiveness ratios in dollars per quality-adjusted life-year were calculated for the first, second, and third 6-month periods during which a patient was receiving clozapine. Sensitivity analyses were performed with more conservative assumptions in 5 alternative scenarios. RESULTS: In the benchmark case, costs per quality-adjusted life-year gained were $61,694, $925,418, and $420,644 for the first, second, and third 6-month periods of clozapine treatment, respectively. In the alternative scenarios, these costs ranged from $7923 to $46,056 for the first 6-month period and from $54,025 to $690,850 for the second and third 6-month periods. CONCLUSIONS: While the costs of monitoring patients with schizophrenia in the first 6-month period of clozapine treatment seem to be justifiable, monitoring thereafter may not be cost-effective because of the very low incidence of agranulocytosis in the later periods.

Substance abuse, community service use, and symptom severity of urban and rural residents with schizoprhenia.

OBJECTIVE: This study examined the relationships of substance abuse, use of community-based services, and symptom severity among rural and urban residents with schizophrenia in the six months after discharge from short-term inpatient care. METHODS: At baseline and six-month follow-up, symptom severity of 139 subjects was assessed using the Brief Psychiatric Rating Scale (BPRS), and substance abuse status was determined using the Structured Clinical Interview for DSM-III-R (SCID). Subjects' reports of mental health service use were confirmed by record review. RESULTS: Although, on average, BPRS scores indicated symptom improvement between baseline and follow-up, symptoms worsened for 27 percent of subjects. Multivariate analysis, adjusted for baseline symptom severity, indicated poorer outcomes for rural residents, substance abusers, and subjects who did not use community services. Symptoms of rural substance abusers who used no community services were worse at follow-up than those of any other subgroup. Nearly half of all subjects had less than monthly contact with community services. The greater likelihood of symptom worsening among rural residents was attributed to their less frequent use of community services. CONCLUSIONS: The findings reinforce the importance of ensuring involvement in community-based services for individuals with comorbid schizophrenia and substance use disorders. Promotion of service use by persons with a dual diagnosis may be particularly critical to the well-being of rural residents with schizophrenia.

Medication noncompliance and substance abuse among patients with schizophrenia.

OBJECTIVE: The study examined the effect of medication noncompliance and substance abuse on symptoms of schizophrenia. METHODS: Short-term inpatients with a diagnosis of schizophrenia were enrolled in a longitudinal outcomes study and continued to receive standard care after discharge. At baseline and six-month follow-up, Brief Psychiatric Rating Scale (BPRS) scores and data on subjects' reported medication compliance, drug and alcohol abuse, usual living arrangements, and observed side effects were obtained. The number of outpatient contacts during the follow-up period was obtained from medical records. Relationships between the dependent variables-medication noncompliance and follow-up BPRS scores-and the independent variables were analyzed using logistic and linear regression models. RESULTS: Medication noncompliance was significantly associated with substance abuse. Subjects who abused substances, had no outpatient contact, and were noncompliant with medication had significantly greater symptom severity than other groups. CONCLUSIONS: Substance abuse is strongly associated with medication noncompliance among patients with schizophrenia. The combination of substance abuse, medication noncompliance, and lack of outpatient contact appears to define a particularly high-risk group.

Predictors of clozapine response in schizophrenia.

The introduction of the atypical neuroleptic, clozapine, has had widespread influence not only on the treatment of the seriously mentally ill patient, but also on new drug development and on hypotheses of the pathophysiology of schizophrenia. While clozapine differs from traditional neuroleptics in its lack of extrapyramidal side effects (EPS), it also is distinct in its profile of neurotransmitter receptor affinities. In our work examining the clinical and biological effects of clozapine in patients with schizophrenia, we have identified the presence of EPS during typical neuroleptic treatment as a consistent predictor of subsequent good response to clozapine. Further, our data suggest that clozapine should not be reserved for the most chronically ill patients, but rather be utilized in patients with less chronic courses of schizophrenia. Biological predictors of clozapine response are consistent with dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action.

Effects of clozapine and fluphenazine treatment on responses to m-chlorophenylpiperazine infusions in schizophrenia.

OBJECTIVE: To explore serotonin function in patients with schizophrenia during typical and atypical neuroleptic treatment. We hypothesized that clinically relevant doses of the atypical neuroleptic clozapine would attenuate responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP). DESIGN AND INTERVENTIONS: m-CPP or placebo was administered intravenously over 90 seconds to patients who had been receiving no medications for at least 3 weeks. m-CPP was also administered during treatment with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine. PATIENTS: Fifteen inpatients (two women and 13 men) who met DSM-III-R criteria for chronic schizophrenia (n = 13) or schizoaffective disorder (n = 2) participated in the study. Mean age (+/- SD) was 33.8 +/- 8.0 years. MAIN OUTCOME MEASURES: Measures of m-CPP effects included plasma cortisol and prolactin, body temperature, and the Brief Psychiatric Rating Scale (BPRS). The final BPRS total score at approximately 12 weeks of treatment was used to assess response to clozapine. RESULTS: m-CPP infusion significantly increased plasma cortisol and prolactin levels in drug-free patients. There was a range of behavioral responses while drug-free, but no statistically significant effects on BPRS total or BPRS factor scores. Clozapine treatment significantly blocked neuroendocrine responses to m-CPP, whereas fluphenazine had no effect. Clozapine also appeared to attenuate behavioral responses. CONCLUSIONS: These results demonstrate that clozapine treatment has potent serotonin antagonist effects in patients with schizophrenia. This may be related to clozapine's therapeutic effects since patients with greater cortisol response to m-CPP while drug-free had a better subsequent response to clozapine.

Clinical investigation of monoamine neurotransmitter interactions.

Monoamine neurotransmitter systems are widely thought to be involved in the pathophysiology of affective disorders and schizophrenia and the mechanism of action of antidepressant and antipsychotic drugs. Previous clinical studies have focused on individual monoamine function in isolation, even though a large number of preclinical studies have demonstrated that monoamine neurotransmitter systems interact with one another. In the present paper, preclinical data on monoamine neurotransmitter interactions are reviewed, and two methods for examining monoamine neurotransmitter system interactions in clinical data are presented. One of the best replicated findings in biological psychiatry is that monoamine metabolites in CSF correlate with one another. The degree of correlation may be in part a measure of the degree of interaction between the parent monoamine neurotransmitter systems. Another approach to studying interactions is the use of HVA/5HIAA and HVA/MHPG ratios as an index of interactions between 5HT-DA and NE-DA. When these methods are applied in schizophrenia, patients are found to have decreased monoamine metabolite correlations compared to normal controls. Metabolite correlations increase significantly after antipsychotic treatment, and the HVA/5HIAA and HVA/MPHG ratios also increase, suggesting that neuroleptics may act in part by strengthening interactions between monoamines. BPRS ratings are negatively correlated with HVA/5HIAA and HVA/MHPG so that patients with higher ratios have fewer symptoms, particularly after treatment. These results provide direct experimental support for hypotheses suggesting that interactions between monoamine neurotransmitters are important in schizophrenia. Some of the effects of the atypical neuroleptic, clozapine, on metabolite correlations and ratios are also discussed.