Cost-effectiveness of clozapine compared with conventional antipsychotic medication for patients in state hospitals.

BACKGROUND: An open-label, randomized controlled trial compared clozapine with physicians'-choice medications among long-term state hospital inpatients in Connecticut. The goal was to examine clozapine's cost-effectiveness in routine practice for people experiencing lengthy hospitalizations. METHODS: Long-stay patients with schizophrenia in a state hospital were randomly assigned to begin open-label clozapine (n = 138) or to continue receiving conventional antipsychotic medications (n = 89). We interviewed study participants every 4 months for 2 years to assess psychiatric symptoms and functional status, and we collected continuous measures of prescribed medications, service utilization, and other costs. We used both parametric and nonparametric techniques to examine changes in cost and parametric analyses to examine changes in effectiveness. We used bootstrap techniques to estimate incremental cost-effectiveness ratios and create cost-effectiveness acceptability curves. RESULTS: Both groups incurred similar costs during the 2-year study period, with a trend for clozapine to be less costly than usual care in the second study year. Clozapine was more effective than usual care on many but not all measures. With the use of effectiveness measures that favored clozapine (extrapyramidal side effects, disruptiveness), bootstrap techniques indicated that, even when a payer is unwilling to incur any additional cost for gains in effectiveness, the probability that clozapine is more cost-effective than usual care is at least 0.80. These findings were not as evident when outcomes where clozapine was not clearly superior (psychotic symptoms, weight gain) were examined. CONCLUSION: Clozapine demonstrated cost-effectiveness on some but not all measures of effectiveness when the alternative was a range of conventional antipsychotic medications.

Efficacy of nurse telehealth care and peer support in augmenting treatment of depression in primary care.

BACKGROUND: Primary care treatment of depression needs improvement. OBJECTIVE: To evaluate the efficacy of 2 augmentations to antidepressant drug treatment. DESIGN: Randomized trial comparing usual care, telehealth care, and telehealth care plus peer support; assessments were conducted at baseline, 6 weeks, and 6 months. SETTING: Two managed care adult primary care clinics. PARTICIPANTS: A total of 302 patients starting antidepressant drug therapy. INTERVENTIONS: For telehealth care: emotional support and focused behavioral interventions in ten 6-minute calls during 4 months by primary care nurses; and for peer support: telephone and in-person supportive contacts by trained health plan members recovered from depression. MAIN OUTCOME MEASURES: For depression: the Hamilton Depression Rating Scale and the Beck Depression Inventory; and for mental and physical functioning: the SF-12 Mental and Physical Composite Scales and treatment satisfaction. RESULTS: Nurse-based telehealth patients with or without peer support more often experienced 50% improvement on the Hamilton Depression Rating Scale at 6 weeks (50% vs 37%; P =.01) and 6 months (57% vs 38%; P =.003) and on the Beck Depression Inventory at 6 months (48% vs 37%; P =. 05) and greater quantitative reduction in symptom scores on the Hamilton scale at 6 months (10.38 vs 8.12; P =.006). Telehealth care improved mental functioning at 6 weeks (47.07 vs 42.64; P =.004) and treatment satisfaction at 6 weeks (4.41 vs 4.17; P =.004) and 6 months (4.20 vs 3.94; P =.001). Adding peer support to telehealth care did not improve the primary outcomes. CONCLUSION: Nurse telehealth care improves clinical outcomes of antidepressant drug treatment and patient satisfaction and fits well within busy primary care settings.

Treatment costs and patient outcomes with use of risperidone in a public mental health setting.

OBJECTIVE: Risperidone's effectiveness in reducing symptoms and its cost were compared with the effectiveness and cost of standard antipsychotic medication among matched groups of outpatients with schizophrenia. METHODS: Data on 56 subjects started on risperidone were compared with data for a matched group of 56 subjects over the 12 months before and after initiation of risperidone. Global Assessment of Functioning (GAF) scores were used to assess effectiveness. Service utilization data were used to calculate the cost of treatment. RESULTS: Total treatment costs for the two groups were not significantly different, although there was a trend toward higher costs in the risperidone group. Monthly GAF scores revealed no group differences in the effectiveness of the medications. CONCLUSIONS: No significant differences in treatment effectiveness or costs were found between the risperidone and comparison groups, despite a trend to higher treatment costs for the risperidone group.

The Program Environment Scale: assessing client perceptions of community-based programs for the severely mentally ill.

The Program Environment Scale (PES) was developed for use with clients of community-based programs for the severely mentally ill. It is intended to fill the gap in available tools for assessing clients' perceptions of program functioning as it affects their "quality of life" in a program. Formal pretests were conducted with 121 clients at 12 randomly selected programs near Washington, DC. The final field test used a revised form (29 domains; 129 items) with 221 clients in 22 programs selected randomly throughout the U.S., including Clubhouse, day treatment, psychosocial rehabilitation, and social club programs. Twenty-three subscales met at least five of eight psychometric criteria for internal consistency and discriminant validity. A 24th subscale was retained because of its substantive importance. Successful subscales cover program atmosphere and interactions (program cares about me, energy level, friendliness, openness, staff-client and client-client respect, reasonable rules, availability of positive physical contact, protection from bad touch, staff investment in their jobs, and confidentiality), client empowerment/staff-client equality (program and treatment empowerment, egalitarian space use), and service components (support for paid work, work importance, emergency access, family activities, housing, public benefits, community activities, medications, substance abuse, and continuity). Subscale validity is indicated by associations of specific service offerings with scores on scales measuring client perceptions of those services, and by an ability to differentiate among program models (i.e., Clubhouses, day treatment programs, and psychosocial rehabilitation programs look different from each other). Subscale scores were not influenced by client characteristics (gender, race, age, diagnosis, number of hospitalizations, length of time in program). The final scale has 97 items and takes about 25 minutes to complete. The PES succeeds in measuring different aspects of programs as clients perceive them. In the programs we visited, directors felt the PES covers the important things they want to know about how clients perceive their program. The PES should become a useful tool both for researchers interested in how client responses to programs may influence their therapeutic outcomes, and for practitioners interested in improving their clients' program experiences and/or increasing convergence of staff and client views of their program.

Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment.

BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age subgroups of schizophrenic patients.

1. The purpose of this retrospective chart review study was to determine whether broad and stringent criteria differentially impact clozapine eligibility in ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients charts were selected from a random cluster sample of mental health patients known to the city and county of San Francisco. Information related to clozapine eligibility was abstracted by trained non-clinical personnel. The impact of subgroup membership on eligibility was examined using logistic regression procedures. 3. Even under the broadest interpretation of FDA requirements for clozapine use, Asian patients were less likely to be eligible, since fewer Asian patients met clozapine treatment requirements. Under more stringent eligibility criteria, older patients were more likely to be excluded from eligibility when TD does not automatically satisfy treatment criteria, and younger patients were more likely to lose eligibility if the number of required adequate medication trials increases to three. 4. Broad eligibility criteria tend to differentially exclude Asian patients while more stringent criteria differentially exclude younger and older patients.

Transition from acute to maintenance treatment: prediction of stabilization.

The stabilization period that follows the exacerbation of a schizophrenic illness represents a critical point in the course of the illness. Successful stabilization is a prerequisite to long-term tenure in the community and the possibility of improvement in functional outcome. In this paper we present an operational definition of stabilization, developed in the context of a study of long-term maintenance treatment that incorporates time, symptomatic equilibrium and consistency of medication dosage. Patients were identified at the time of hospitalization and followed prospectively to determine whether or not they met stabilization criteria. Characteristics that predicted successful stabilization included measures drawn from the domains of patient personal characteristics and psychiatric history, symptoms of psychopathology and side effects in response to initial treatment and family judgments. These patients were treated primarily with fluphenazine decanoate, and five distinct dosing strategies with this agent were identified retrospectively. The dosing strategies distinguished the length of time to subsequent stabilization. The implications of these findings for clinical management of schizophrenia are discussed.

Pharmacoeconomics of antipsychotic drug therapy.

Treatment cost can have a dramatic effect on treatment availability, and clinicians may find themselves unable to provide expensive treatments they believe their patients should receive. The introduction of new, premium-priced antipsychotic medications has provided visible examples of this problem. Cost considerations must be part of treatment decisions, since resources are often insufficient to provide all potentially helpful treatments. However, the key question regarding expensive drugs is whether other savings can be expected to offset the higher drug price, or if not, whether improved effectiveness justifies the added cost. Pharmacoeconomic research attempts to integrate relevant information on both effectiveness and cost so that clinicians, patients, and other decision-makers can make meaningful treatment choices. This article presents a conceptual framework for cost-effectiveness analysis, illustrates pharmacoeconomic methods with studies of the cost-effectiveness of clozapine treatment, and describes the steps in designing cost-effectiveness research on novel antipsychotic agents.

Effect of Proposition 187 on mental health service use in California: a case study.

In this DataWatch we examine whether the passage of California's Proposition 187 affected the use of mental health services in San Francisco County. Using time-series analyses, we identified a 26 percent decrease in the initiation of outpatient mental health services by younger Hispanics at selected service sites after the passage of Proposition 187 in November 1994. Further analyses suggest that decreased use of outpatient mental health services by young Hispanics was associated with their subsequent increased use of crisis services. Other studies of Proposition 187's effect on mental health service use in California are needed to corroborate the findings of this case study.

Clozapine's effectiveness for patients in state hospitals: results from a randomized trial.

In our study, we examined the effectiveness of clozapine and compared it to the array of medication alternatives typically used in the public sector. Long-term patients in Connecticut's state hospitals who met Food and Drug Administration criteria for clozapine use were invited to participate in this randomized open-label study. Participants (N = 227) were followed for 2 years. Compared with usual care, clozapine was associated with significantly greater reductions in side effects, disruptiveness, and hospitalization, but was not more effective in reducing symptoms or improving quality of life. The groups did not differ in likelihood of being discharged; however, once discharged, clozapine patients were less likely to be readmitted. The results of our study suggest that, compared with the flexible range of medication alternatives available, clozapine is an effective agent. However, at least with this patient population, clozapine did not produce the dramatic improvements is symptomatology or hospital utilization reported in clinical efficacy trials or suggested by mirror-image studies.

Clozapine eligibility among state hospital patients.

Connecticut State Hospital's entire resident population (n = 1,300) was screened on an arbitrary target day to determine eligibility for clozapine. Sixty percent of 803 patients with schizophrenia or schizoaffective disorder diagnoses met Food and Drug Administration (FDA)- approved criteria for clozapine use as judged by review of past medication trial records and by the responsible physicians. Eighty-eight percent of these patients were medically cleared, and of those cleared, 63 percent agreed to clozapine treatment. Of the patients who began a clozapine trial, 76 percent were still taking the drug 12 months later. Preliminary findings from a randomized trial of clozapine versus usual care (n = 227) indicate that discharge rates associated with clozapine and usual care do not differ. Once discharged, however, patients assigned to clozapine are less likely to be readmitted. Hence, clozapine may be more cost-effective than usual care. However, before savings can be realized, State governments will have to make up-front investments of approximately $140 million simply to give patients hospitalized on a single day a year's access to clozapine.

Effects of stringent criteria on eligibility for clozapine among public mental health clients.

OBJECTIVE: This study estimated rates of eligibility for treatment with clozapine among clients in a public mental health system using criteria with various degrees of restrictiveness. METHODS: A stratified, random cluster sample of 293 clients was selected from among all clients with schizophrenic disorders known to the mental health system of the city and county of San Francisco during 1991. Data on variables associated with eligibility for clozapine were abstracted from clinical records, and eligibility was estimated using broad and stringent criteria. RESULTS: An estimated 42.9 percent of the clients were eligible for clozapine using broad eligibility criteria that included a diagnosis of schizophrenia or schizoaffective disorder, two previous neuroleptic trials of at least 600 mg per day chlorpromazine equivalents for at least four weeks or tardive dyskinesia, Global Assessment of Functioning score less than 61, and no contraindications. Eliminating eligibility due to tardive dyskinesia alone, excluding persons with schizoaffective disorder, requiring six-week medication trials, and requiring three adequate medication trials instead of two resulted in substantial reductions in the rate of eligibility. CONCLUSIONS: Varying interpretations of the criteria for clozapine treatment listed in the medication package insert dramatically affect patients' eligibility for clozapine. Mental health agencies should endeavor to maintain a balance between restricting use of clozapine due to cost and providing it to the full spectrum of patients who might benefit from the medication.

Prevention of depression with primary care patients: a randomized controlled trial.

The prevention of major depression is an important research goal which deserves increased attention. Depressive symptoms and disorders are particularly common in primary care patients and have a negative impact on functioning and well-being comparable with other major chronic medical conditions. The San Francisco Depression Prevention Research project conducted a randomized, controlled, prevention trial to demonstrate the feasibility of implementing such research in a public sector setting serving low-income, predominantly minority individuals: 150 primary care patients free from depression or other major mental disorders were randomized to an experimental cognitive-behavioral intervention or to a control condition. The experimental intervention group reported a significantly greater reduction in depressive levels. Decline in depressive levels was significantly mediated by decline in the frequency of negative conditions. Group differences in the number of new episodes (incidence) of major depression did not reach significance during the 1-year trial. We conclude that depression prevention trials in public sector primary care settings are feasible, and that depressive symptoms can be reduced even in low-income, minority populations. To conduct randomized prevention trials that can test effects on incidence with sufficient statistical power, subgroups at greater imminent risk have to be identified.

Patterns of substance use in schizophrenia: a Markov modeling approach.

Markov models were used to examine patterns of substance use and global functioning in a sample of 100 schizophrenic outpatients over an 18 month period. Patterns of changes in substance use and functional status were stable across the evaluation period. Persons remaining in any substance use or functional state for two evaluation periods were highly likely to continue in the same state. Tests of two common causal hypotheses about relationships between substance use and functional status yielded partial support for the hypothesis that substance use leads to functional impairment, but did not support the hypothesis that functional impairment leads to substance use. Furthermore, there was no evidence of any increase in overall substance use or of substance use leading to treatment dropout. These analyses illustrate a promising approach to key questions about substance use in schizophrenia.

Benzodiazepine augmentation of neuroleptics in treatment-resistant schizophrenia.

A significant minority of patients with schizophrenia fail to respond to neuroleptic medication alone. In some of these patients, adjunctive treatment with benzodiazepines may prove beneficial. Preclinical studies suggest that benzodiazepines significantly decrease brain dopamine release and turnover, perhaps by augmenting gamma-aminobutyric acid (GABA) inhibition of dopamine neuron activity. Double-blind clinical studies, however, have not conclusively established a role for benzodiazepines in the treatment of schizophrenia, and it seems likely that some patients respond favorably, whereas others do not. We review preliminary new observations that approximately half of a group of treatment-resistant patients, studied in a double-blind treatment protocol, demonstrated clinically significant antipsychotic responses to adjunctive alprazolam. We also briefly describe long-term efficacy of alprazolam in several patients whom we have followed in open-label clinical settings. Possible predictors or biological concomitants of benzodiazepine responsivity, which may aid in delineating distinct subgroups of patients, are discussed, and recommendations for future research are presented.

Dangerous behavior and changes in treatment course.

The association of dangerous behavior with the course of subsequent treatment was examined by comparing treatment courses of 45 severely mentally disabled patients identified as dangerous after an incident of dangerous behavior was noted in their clinical records with treatment courses of 122 severely mentally disabled patients who had no recorded incidents of dangerous behavior. The correlation of dangerousness with subsequent restrictiveness of treatment is clearly present in 6 of the 9 variables examined; the relationship generalizes across two rather different CMHC sites.

Demographic characteristics, treatment history, presenting psychopathology and early course in schizophrenia. Treatment Strategies in Schizophrenia Collaborative Study Group.

Subject heterogeneity increases generalizability of study findings so long as site differences do not interact with treatment effects. Of 51 baseline characteristics of 234 patients, 31 show significant site differences. Of 33 baseline demographic, treatment history, and presenting symptom items, site differences were seen on 16. This heterogeneity emphasizes the importance of examining site interactions with other effects. The first opportunity to examine such interactions is in the prediction of patient stabilization following the index acute episode. Among the 33 demographic, treatment history, and presenting symptom variables, 11 significantly predicted this short-term outcome. Only 2 of these 33 variables showed site-by-baseline interactions in predicting stabilization, most likely due to chance sampling fluctuations. Thus, site heterogeneity is adding generality without confounding the predictions.