Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.

BACKGROUND: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. METHODS: Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type. RESULTS: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). CONCLUSIONS: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. TRIAL REGISTRATION: European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.

Safety and effectiveness of olanzapine in monotherapy: a multivariate analysis of a naturalistic study.

BACKGROUND: This study investigated safety and effectiveness of olanzapine in monotherapy compared with conventional antipsychotics in treatment of acute inpatients with schizophrenia. METHOD: This was a prospective, comparative, nonrandomized, open-label, multisite, observational study of Spanish inpatients with an acute episode of schizophrenia. Data included safety assessments with an extrapyramidal symptoms (EPS) questionnaire and the report of spontaneous adverse events, plus clinical assessments with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate methodology was used to more adequately determine which factors can influence safety and effectiveness of olanzapine in monotherapy. RESULTS: 339 patients treated with olanzapine in monotherapy (OGm) and 385 patients treated with conventional antipsychotics (CG) were included in the analysis. Treatment-emergent EPS were significantly higher in the CG (p<0.0001). Response rate was significantly higher in the OGm (p=0.005). Logistic regression analyses revealed that the only variable significantly correlated with treatment-emergent EPS and clinical response was treatment strategy, with patients in OGm having 1.5 times the probability of obtaining a clinical response and patients in CG having 5 times the risk of developing EPS. CONCLUSION: In this naturalistic study olanzapine in monotherapy was better-tolerated and at least as effective as conventional antipsychotics.

Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia: a multivariate analysis of a large naturalistic study in the hospital setting.

BACKGROUND AND OBJECTIVE: This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness. PATIENTS AND METHOD: This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients' entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed. RESULTS: Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007). CONCLUSIONS: Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.

Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia: a multivariate analysis of a large naturalistic study in the hospital setting

FUNDAMENTO Y OBJETIVO: Este estudio evaluó la seguridad y la efectividad del antipsicótico atípico olanzapina en el tratamiento hospitalario de la esquizofrenia, así como los patrones de uso deolanzapina y su relación con la seguridad y la efectividad. PACIENTES Y MÉTODO: Se trató de un estudio prospectivo, comparativo, no aleatorizado, abierto, observacional, de 848 pacientes con esquizofrenia (Clasificación Internacional de Enfermedades, décima edición) hospitalizados a causa de un episodio psicótico agudo. Los datos se recogieron durante la totalidad de su estancia hospitalaria. La seguridad del tratamiento antipsicótico se evaluó mediante un cuestionario de síntomas extrapiramidales basado en la escalaUdvalg for Kliniske Undersøgelser, así como mediante la recogida de efectos adversos autorreferidos por el paciente. La situación clínica se evaluó mediante la Escala Breve de EvaluaciónPsiquiátrica (BPRS) y la escala de Impresión Clínica Global-Severidad de la Enfermedad (CGIS).Se utilizó un método estadístico multivariante. RESULTADOS: Los pacientes tratados con olanzapina en monoterapia mostraron el menor riesgo de desarrollar síntomas extrapiramidales, mientras que los tratados con antipsicóticos convencionales mostraron el mayor riesgo (p < 0,001). Los pacientes tratados con olanzapina en monoterapia(incluso aquellos con síntomas positivos prominentes) demostraron una mayor tasa de respuesta que los tratados con antipsicóticos convencionales (p = 0,007).CONCLUSIONES: La olanzapina constituye un tratamiento seguro y efectivo para pacientes con un episodio agudo de esquizofrenia tratados en el ámbito hospitalario, incluso para aquellos con síntomas positivos o de agitación prominentes

BACKGROUND AND OBJECTIVE: This study assessed the safety and effectiveness of the atypical antipsychoticolanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness. PATIENTS AND METHOD: This was a prospective, comparative, nonrandomized, open-label, observationalstudy of 848 patients with schizophrenia (International Classification of Diseases, 10thedition) hospitalized due to an acute psychotic episode. Data were collected during patients’ entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale(BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed. RESULTS: Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (evenpatients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007).CONCLUSIONS: Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms

Safety, effectiveness, and quality of life of olanzapine in first-episode schizophrenia: a naturalistic study.

OBJECTIVE: This study evaluated the effectiveness, safety, and quality of life (Qol) offered by olanzapine in first-episode schizophrenia. METHOD: One hundred and eighty-two patients with first-episode schizophrenia (ICD-10) drawn from a larger, naturalistic, study were evaluated after 6 months of treatment with olanzapine, risperidone, or conventional antipsychotics (CA). Clinical status was assessed using the Clinical Global Impression-Severity (CGI-S) and Global Assessment of Function (GAF). AWAD and EuroQol scales were used to evaluate patients' attitude towards medication and Qol, respectively. RESULTS: Subjects treated with olanzapine, risperidone, and CA showed similar improvements on CGI-S and GAF. Treatment-emergent, extrapyramidal symptoms were significantly lower in olanzapine-treated patients (17.8%) than in the risperidone (46.4%) and CA (62.2%) groups. Compared to CA, olanzapine and risperidone showed significantly greater improvement on the visual analog scale of EuroQol. Olanzapine-treated patients also showed significantly improved AWAD scores. CONCLUSIONS: In first-episode schizophrenia, atypical antipsychotics were effective, and improved Qol. Olanzapine had a lower incidence of extrapyramidal symptoms and better subjective acceptance of medication.

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

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.

Bilateral anterior capsulotomy for refractory obsessive-compulsive disorders.

A prospective study on the effects of bilateral anterior capsulotomy in patients with refractory obsessive-compulsive disorder (OCD) is presented. A total of 18 procedures were performed in 15 patients. The mean duration of the OCDs was 18.1 +/- 5.6 years (range 11-26 years). The mean total Yale-Brown Scale (Y-BOCS) score was 29.67 and mean Global Assessment of Functioning was 43.61. The results throughout the follow-up period remained the same as at 1 month postoperatively. The observed mean recovery on the Y-BOCS was 33.2% (p = 0.017). 52.9% of the patients showed a 33% recovery, 29.4% of the cases showed a 50% recovery and 17% showed a 66% recovery. Global Assessment of Functioning recovered by 19% (p = 0.111). No cognitive deficit was disclosed by neuropsychological screening tests. Complications were observed in 3 cases, 1 with transitory hallucinations, 1 with a single epileptic seizure and 1 case who developed a progressive behavior disorder that became permanent. We conclude that bilateral anterior capsulotomy is a safe and effective procedure.

Eficacia de la psicocirugía en el trastorno obsesivo-compulsivo. Resultados preliminares (septiembre, 2002) / Effectiveness of psychosurgery in obsessive-compulsive disorder.

Tras una concisa introducción al trastorno obsesivo-compulsivo (T.O.C.) resistente, a la historia de la psicocirugía y en concreto a la técnica neuroquirúrgica de la capsulotomía bilateral anterior, se describe el Protocolo de Psicocirugía del T.O.C. resistente del Hospital de Mutua de Terrassa. Dicho protocolo se halla en marcha desde 1998, habiéndose valorado 38 solicitudes y dando lugar a 18 intervenciones de psicocirugía mediante capsulotomía bilateral anterior por termocoagulación, hasta Septiembre de 2002 y de su seguimiento durante un año. Se informa de los resultados preliminares valorándose: La Escala de Yale-Brown para Obsesiones-Compulsiones (Y-BOCS) total y las subescalas para obsesiones y compulsiones, los cuestionarios de Hamilton y Beck para depresión y STAI-estado para la ansiedad y la Escala de Evolución de la Actividad Global (E.E.A.G.) del Eje V del DSM-IV. Así como de una batería básica de evolución neuropsicologica compuesta por: los cubos de Kohs, la medida de la memoria visual inmediata y a medio plazo (WMS-R) del test del trazo A y B (TMT). Como medida principal de respuesta la escala Y-BOCS basal de 29,4 paso a 19,1 al mes y al 17,3 al año, con una mejoría media del 332 por ciento al mes. Un 53 por ciento de pacientes mejoraron, tomando como criterio de respuesta la disminución del 33 por ciento de su puntuación basal en la Y-BOCS total. No se objetivó empeoramiento en ninguna de las escalas neuropsicologicas utilizadas. Tan sólo 3 pacientes presentaron complicaciones tras la capsulotomía (AU)