The European Schizophrenia Outpatient Health Outcomes (SOHO) study: rationale, methods and recruitment.

OBJECTIVE: The objective of the European Schizophrenia Outpatient Health Outcomes (SOHO) study is to understand the comparative costs and outcomes of antipsychotic drug treatment, with specific focus on olanzapine. The study will also provide a large database for research into the treatment and outcome of schizophrenia. The role of observational studies in the assessment of the effectiveness of antipsychotic agents is reviewed, and the rationale, design and recruitment issues surrounding the SOHO study are presented. METHOD: SOHO is a 3-year, prospective, observational study of the health outcomes associated with antipsychotic treatment in Europe. RESULTS: Over 10 000 patients have been recruited from 10 countries. Baseline evaluation included measures of clinical status, social functioning, quality of life, service use and pharmacological treatment. Patients will be followed for 3 years. CONCLUSION: The SOHO study will complement randomized controlled trial findings on the treatment of schizophrenia and will address relevant clinical and policy research questions.

Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.

OBJECTIVE: The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. METHODS: The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score < or = 4. RESULTS: A total of 2657 patients were included in the analysis. The initial and overall mean daily doses for the 3 groups were as follows: OLZ, 12.2 and 13.0 mg, respectively; RIS, 5.2 and 5.4 mg; and HAL, 13.9 and 13.6 mg. Initial and overall median daily doses were the same in each group: OLZ, 10 mg; RIS, 6 mg; and HAL, 10 mg. A significantly lower proportion of OLZ-treated patients (36.9%) experienced EPS compared with RIS-treated (49.6%) and HAL-treated (76.0%) patients (P < or = 0.001). A significantly lower proportion of patients in the OLZ group (47.8%) experienced adverse events compared with patients in the RIS (57.2%) and HAL (79.8%) groups (P < or = 0.001). A significantly greater proportion of OLZ-treated patients (37.3%) were responders compared with RIS-treated patients (31.5%) (P < 0.05). In all 3 groups, patients who had an initial CGI score > or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001). CONCLUSION: The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.

[Economic comparison of olanzapine versus haloperidol in treatment of schizophrenia in France]. / Comparaison économique de l'olanzapine versus halopéridol dans le traitement de la schizophrénie en France.

PURPOSE: The purpose of this study is to provide an economic comparison of olanzapine-treated and haloperidol-treated patients from the subset of French patients who participated in a large, international, randomised clinical trial in schizophrenia. METHODS: Patients were evaluated from randomisation until discontinuation, drop out or completion of the 52-week study. The primary clinical measure was "clinically important response" (derived from BPRS total scores). The secondary measure was "clinically important improvement" (derived from CGI severity of illness scores). The primary economic measure was mean per diem, per patient total direct medical costs. RESULTS: A total of 275 French patients where included in the study. Demographics and other baseline differences between olanzapine- and haloperidol-treated patients were not statistically significant. Olanzapine-treated patients (205 +/- 142 days) experienced significantly (p < 0.001) longer evaluation periods than haloperidol-treated patients (132 +/- 129 days). Olanzapine-treated patients (54%) were significantly (p = 0.03) more likely to experience a clinically important response than haloperidol-treated patients (40%). Olanzapine-treated patients (69%) were significantly (p = 0.02) more likely to experience clinically important improvement than haloperidol-treated patients (54%). The mean per diem, per patient total direct medical cost was statistically lower (p = 0.033) for olanzapine-treated patients (FF619 +/- 509) compared to haloperidol-treated patients (FF756 +/- 478). CONCLUSION: Olanzapine treatment was associated with significantly better clinical outcomes and per diem total direct medical cost than haloperidol treatment. The findings indicate that olanzapine is dominant compared to haloperidol for the treatment of schizophrenia, in the context of analysed data. These findings produce increased relevance in France to the existing evidence supporting olanzapine's cost and effectiveness profiles.

Concomitant therapy with anxiolytics or hypnotics and maintenance of initial SSRI therapy.

We conducted a retrospective analysis to evaluate the relationship between anxiolytic or hypnotic therapy and maintenance of therapy with selective serotonin reuptake inhibitors (SSRIs). Subjects were 654 patients who received anxiolytics or hypnotics early in SSRI therapy (study group ) and 15,172 patients who did not (controls). Maintenance of SSRI therapy was evaluated during the 6 months after start of therapy and included days of initial SSRI therapy and rates of discontinuation, defined as a break of more than 30 days. Rates of discontinuation in study and control groups (84% and 77%, p=0.001) and average days of initial SSRI therapy (77 and 94 days, p<0.0001) were statistically different. Thus patients receiving anxiolytic or hypnotics in the first 60 days of therapy were less likely to continue initial SSRI therapy.

Selective serotonin reuptake inhibitor utilization patterns: consistency across research designs.

We examined the impact of commonly applied selection criteria on the ability of patients who are initiating antidepressant therapy to reach a stable pattern, which was defined as receipt of only the initial agent at the initial dose for 90 or more consecutive days. Patients in a large US prescription database who initiated fluoxetine, paroxetine, or sertraline therapy between February and April of 1995 were categorized as with (typical design) and without (relaxed design) commonly applied selection criteria. The percentage of patients achieving a stable pattern was then determined. We found that this percentage was significantly higher with the relaxed design (typical, 28.8%; relaxed, 32.4%) and for patients initiating fluoxetine therapy (>5.5% higher than for those initiating paroxetine or sertraline therapy). The results for fluoxetine were consistent across designs, whereas comparisons between paroxetine and sertraline yielded mixed results. Therefore, the relative relationship of the stable pattern is robust across designs for fluoxetine but not for paroxetine and sertraline. Further, application of commonly applied selection criteria may make a sample less representative and reduce the measured rates of stable antidepressant use, potentially leading to underestimation of the benefits of pharmacotherapy.

Outpatient antidepressant utilization in a Dutch sick fund.

OBJECTIVE: To identify quality improvement opportunities in the management of depression by evaluating patterns of antidepressant use and concurrent use of anxiolytics or sedative/hypnotics among patients who initiated therapy with amitriptyline, fluoxetine, fluvoxamine, or paroxetine. DESIGN: A longitudinal, retrospective study using electronic prescription data from a Dutch sick fund, ZAO Zorgverzekeringen. PATIENTS AND METHODS: The study patients (n = 2,554) initiated therapy between October 1, 1994 and December 31, 1995. Follow-up periods were 6 months (antidepressant use) and 60 days (concurrent anxiolytic and sedative/hypnotic use). RESULTS: The three key findings were as follows: (1) the majority of patients received less than 4 months of therapy (more common for patients receiving amitriptyline); (2) the average daily doses for initial prescriptions for all four study drugs were below the recommended therapeutic minimums for depression (overall and final amitriptyline doses also were consistently low); and (3) the incidence of concurrent anxiolytic and sedative/hypnotic use during days 2-60 after antidepressant therapy initiation was 18.2%. CONCLUSION: The study suggests that patients in this Dutch sick fund were not likely to receive either adequate antidepressant doses or adequate durations of therapy relative to Dutch guidelines for the treatment of depression. These findings are consistent with findings in other Dutch, European, and US studies and may present opportunities for quality improvement.

Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen?

This study retrospectively examines the one-month concomitant use of cytochrome P450 2D6 or 3A4 metabolized medications in 544,309 patients who were also receiving selective serotonin reuptake inhibitors (SSRIs). Overall, 25.53% of SSRI patients experienced concomitant use with at least one of the 33 studied CYP 2D6 or 3A4 metabolized medications. Certain drugs and drug classes were more likely to be used concurrently among SSRI patients (e.g., benzodiazepines, tricyclic antidepressants, calcium channel blockers). Similarly, of the SSRI patients experiencing concomitant use, this concurrent use was twice as likely with cytochrome P450 medications metabolized by the 3A4 isoenzyme as with those metabolized by the 2D6 isoenzyme. Finally, the vast majority (80.9%) of SSRI patients experiencing concomitant use did so with one CYP 2D6 or 3A4 metabolized medication. In sum, concomitant use generally was not extensive and did not appear to be differential among the fluoxetine, paroxetine, or sertraline patient comparison groups.

Concomitant use of anxiolytics and hypnotics with selective serotonin reuptake inhibitors.

A retrospective drug utilization analysis was conducted to compare concomitant use of anxiolytics and hypnotics among patients who received selective serotonin reuptake inhibitors (SSRIs). Data were extracted from an administrative prescription claims database. Patients must have been 18 to 64 years of age, without antidepressant, anxiolytic, or hypnotic use before SSRI therapy initiation, and without the use of antidepressants, other than the original SSRI, after SSRI therapy initiation. The study sample included 117,319 patients. Concomitant anxiolytic use for the total sample was 9.8%. Concomitant anxiolytic use rates for the comparison groups were: fluoxetine, 9.5%; paroxetine, 11.4%; and sertraline, 9.5%. Concomitant hypnotic use for the total sample was 2.8%. Concomitant hypnotic use rates for the comparison groups were: fluoxetine, 2.5%; paroxetine, 3.5%; and sertraline, 2.8%. The majority of concomitant anxiolytic and hypnotic use was initiated on the same day as SSRI therapy initiation. The anxiolytic and hypnotic concomitant use rates for fluoxetine and sertraline patients were significantly lower than the concomitant use rates for paroxetine patients. An understanding of the clinical, quality-of-life, and economic implications of the concomitant use differences will require further study.

The use of two measures of health-related quality of life in HIV-infected individuals: a cross-sectional comparison.

Two measures of health-related quality of life in 65 HIV-infected individuals were compared in a cross-sectional design. The Quality of Well-Being Scale (QWB) results in a single score ranging from death to perfect health. The MOS-HIV Health Survey (MOS-HIV, 34-item version) gives scores in 11 dimensions. The QWB score distinguished subjects with AIDS from those who were asymptomatic (p = 0.027). For the seven multi-item scales of the MOS-HIV, Cronbach's alpha ranged from 0.85-0.95, indicating good internal consistency reliability. Clinical HIV-infection status was significantly associated with the dimensions of Overall Health (p = 0.002), Role Function (p = 0.022), Social Function (p = 0.037), Energy/Fatigue (p = 0.027) and Health Distress (p = 0.025). All eleven dimensions of the MOS-HIV were significantly correlated with the QWB score (Spearman's coefficient = 0.405-0.670; for all, p < 0.01) and the QWB score could be predicted from the MOS-HIV dimension scores using multiple regression. The QWB and the MOS-HIV may be useful in assessing health-related quality of life in patients infected with HIV.

Selective serotonin reuptake inhibitor dose titration in the naturalistic setting.

Little information exists regarding the use of selective serotonin reuptake inhibitors (SSRIs) in the naturalistic setting. The Regenstrief Medical Record System was used to analyze the dosing of SSRIs in the outpatient population of an urban teaching hospital. A cohort of 3350 patients was extracted, of whom 2859 had received fluoxetine and 460 sertraline. This cohort received 21,079 prescriptions. (The 31 patients who were prescribed paroxetine were eliminated from further analysis.) The mean daily dose for all patients receiving fluoxetine was 21 +/- 6 mg for the first prescription dispensed and 25 +/- 11 mg for the ninth. For fluoxetine-treated patients with depression included on their computerized medical problem list, the mean daily dose was 21 +/- 6 mg for the first prescription and 26 +/- 12 mg for the ninth. A mean of 5.0% of all patients continuing fluoxetine therapy had their daily dose increased with each prescription refill during the first nine prescriptions. The mean daily dose for all patients receiving sertraline was 59 +/- 28 mg for the first prescription and 117 +/- 66 mg for the ninth. For sertraline-treated patients with depression included on their computerized medical problem list, the mean daily dose was 57 +/- 25 mg for the first prescription and 110 +/- 65 mg for the ninth. A mean of 14.9% of all patients continuing sertraline therapy had their daily dose increased with each prescription refill during the first nine prescriptions. The frequency of sertraline dose increases was 2 to 3 times the rate for fluoxetine. Because increases in daily doses typically result from inadequate control of symptoms of depression, these findings may reflect fluoxetine's greater effectiveness in controlling symptoms during the initial stages of therapy in the naturalistic setting.