Fernando Cañas

Safety and effectiveness of olanzapine versus conventional antipsychotics in the acute treatment of first-episode schizophrenic inpatients.

OBJECTIVE To assess the safety and effectiveness of olanzapine compared to typical antipsychotics in the treatment of first-episode schizophrenics in acute psychiatric inpatient wards. METHODS Data were collected from a prospective, comparative, nonrandomized, open, observational study of 904 inpatients with schizophrenia. One hundred and fifty-eight patients fulfilled the criteria for first-episode schizophrenia, defined as (1) the International Classification of Diseases: Mental and Behavioral Disorders, 10th ed. (ICD-10) diagnosis of schizophrenia, (2) antipsychotic nai;ve, and (3) a course of illness of less than 5 years. Eighty-nine (56.3%) of these patients were assigned to the olanzapine treatment group (OLZ) and 69 (43.7%) to the control group that received treatment with conventional antipsychotics (CON). Safety was evaluated in terms of the spontaneous adverse events reported and a specific questionnaire for extrapyramidal symptoms (EPS). Clinical status was measured by means of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Severity (CGI-S). Clinical response was defined as the baseline-endpoint decrease in BPRS>40% plus an endpoint BPRS<18 or an endpoint CGI</=3. RESULTS The rate of clinical response to treatment in the OLZ was 76.7%, compared to 54.4% in the CON (chi(2)=8.48; P=.003). Olanzapine was significantly more effective than conventional antipsychotics in lowering the total BPRS score (P=.0003), as well as each of the following BPRS subscales: positive symptoms (P=.0019), negative symptoms (P<.0001), depression (P=.018), and agitation (P=.007), even after mean scores were adjusted for their baseline value and disease duration. Olanzapine also proved to be significantly superior to conventional antipsychotics in lowering mean CGI scores (P=.013). The frequency with which new EPS appeared, or previously existing ones worsened, was significantly greater in the CON than in the OLZ (55.1% vs. 13.5%; P<.001). Anticholinergics were needed more frequently in the CON than in the OLZ (58.0% vs. 6.7%; P<.0001). CONCLUSIONS The results of this observational, naturalistic study show that olanzapine is safe and effective in a nonselected sample of acute, first-episode schizophrenic inpatients.

Management of agitation in the acute psychotic patient--efficacy without excessive sedation.

Rapid-acting intramuscular (IM) formulations of atypical antipsychotics offer a significant advance over IM haloperidol in the short-term management of acute schizophrenic episodes. Several short-term open-label randomised studies, typically enrolling two- to three-hundred patients, have compared an atypical antipsychotic with haloperidol. These studies show that IM ziprasidone, IM olanzapine and IM aripiprazole are at least as effective and better tolerated than IM haloperidol, with lower extrapyramidal side effects. Successful transitions from an IM to oral formulation of the same agent have been performed in double-blind randomised trials assessing haloperidol, olanzapine, ziprasidone and aripiprazole. Avoiding over-sedation is now recognised as important, and randomised clinical trial data indicate that oral ziprasone, quetiapine, and IM olanzapine have high dose-related sedative potential while oral risperidone and IM aripiprazole have low sedative potential. In summary, IM formulations of atypical antipsychotics are recommended as first-line treatment of acute agitation with subsequent transition to an oral formulation of the same agent for ongoing management.

Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

Safety of olanzapine versus conventional antipsychotics in the treatment of patients with acute schizophrenia. A naturalistic study.

BACKGROUND Conventional antipsychotics although effective in treating acute psychotic and behavioural symptoms are subject to certain limitations due to the high incidence of side effects associated, mainly extrapyramidal symptoms (EPS), and insufficient response shown in some cases. EPS are a major factor in neuroleptic non compliance and high relapse rates among patients. This study was designed to assess the safety and effectiveness of olanzapine compared to typical antipsychotics drugs in the treatment of schizophrenic inpatients at acute psychiatric in-patient units. METHOD Data from 904 patients schizophrenic patients (F20 of ICD10, WHO) were collected in this prospective, comparative, non-randomized, open and observational study. Patients were followed during their entire hospital stay. Safety was assessed through the collection of spontaneous adverse events and a specific extrapyramidal symptoms questionnaire (EPS). Clinical status was measured through the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Improvement (PGI) and the Nursing Observational Scale for In-patient Evaluation (NOSIE). RESULTS A total of 483 patients received olanzapine (olanzapine group, OG), and 421 received typical antipsychotics (control group, CG). Treatment emergent EPS, or worsening of previous EPS were statistically significantly higher in the CG (P=0.001). Responder rate was statistically greater in the OG (P<0.001). Mean change in BPRS-total, BPRS-negative, BPRS-agitation subscales and PGI was significantly higher in the OG (P<0.001). Mean decrease in CGI, BPRS positive and BPRS depression sub-scales was also significantly lower (P< or =0.05). Mean change in the NOSIE scale was similar between both groups. CONCLUSION Olanzapine has been shown to be better tolerated in comparison with conventional antipsychotics in a large unselected sample of acutely psychotic schizophrenic in-patients. Its effectiveness may be greater than that of conventional antipsychotics.

Treatment adherence and quality of sleep in schizophrenia outpatients

Abstract Objective. Patients with schizophrenia (SZ) often present sleep complaints, and patients with sleep disturbances are at a greater risk for symptom worsening after antipsychotic discontinuation. Long-term adherence to antipsychotic treatment remains a challenge for clinicians, and the relationship between quality of sleep and treatment adherence in SZ outpatients has been poorly studied. Methods. In this cross-sectional, non-interventional study, 811 adult outpatients with a diagnosis of SZ were divided into two groups according to the presence (or absence) of sleep disturbances, and assessed using measures of symptom severity, quality and patterns of sleep, adherence/compliance to treatment, and family support degree. Results. Patients with sleep disturbances were significantly more symptomatic (p < 0.0001), and scored significantly higher on the Pittsburgh Sleep Quality Index (PSQI) as compared with patients without sleep disturbances (p < 0.0001). More compliant patients showed less sleep disturbances (p < 0.0001); moreover, patients with worse compliance to pharmacological treatment showed significantly higher scores on the PSQI (p < 0.0001). Regarding family support degree, patients with sleep disorders presented a lower family support (p = 0.0236), and patients with worse treatment adherence had worse family support (p < 0.0001). Conclusions. Our findings show that SZ outpatients reporting sleep disturbances show greater symptom severity, and worse adherence/compliance to treatment, as well as a lower family support.