Monotherapy Olanzapine Research Articles

Treatment resistant FEP (first episode of psycosis) with neuroanatomical findings

IntroductionPresentantion of the first psychotic episode of a young man and the investigation of the efficacy of treatment with olanzapine and after cariprazine.ObjectivesAssessing the response to treatment of cariprazine in a psychotic patient with relevant neuroanatomical findings.MethodsA 25-year old man was admitted to the psychiatric intensive care due to his agggressive behavior and verbal abuse, threatening to kill them both. His medical history included long periods of negatively affected mood, social isolation and talking to himself according to his familyResultsWhent the patient was admitted he was very anxious, alert and extremely aggressive. During the interview he admitted auditory and visual hallucinations alongside delusional ideation with a particular aggression towards his father.Upon admission his PANSS score was 121. positive scale score was 23.The patient was treated initially with monotherapy olanzapine, gradually increased up to 20mg OD. Olanzapine caused asymptomatic transaminasemia, a relatively common adverse effect. At this point a change in medication was made and olanzapine was stopped and cariprazine was added gradually increasing its dose from 1,5mg to 6mg OD.Interestingly the medical investigations (brain CT scan) indicated a calcification in falx cerebri.After a period of 48 days since admission the patient was clinically improved and was discharged. His PANSS score was 72. Positive scale was 10.ConclusionsThe use of cariprazine as a treatment for a first psychotic episode of a young male improved his PANSS score after a 22-day treatment. According to the literature neuroanatomical findings have been associated with poor prognosis regarding the course of the illness. There needs to be further investigation on the efficacy of the long term treatment for this patient.Disclosure of InterestNone Declared

M106 - GENE CO-EXPRESSION REVEALS PATHWAYS OF CONVERGENCE OF SCHIZOPHRENIA RISK GENES

Background Schizophrenia (SCZ) is associated with genetic factors, and specific risk loci have recently been identified. Still, the biology and functional or clinical translation of SCZ risk genes remain largely unknown. At least some of the Psychiatric Genomic Consortium (PGC) genetic variants control gene expression [1] . Since the expression of individual genes is co-regulated and results in the co-expression of gene sets, we hypothesized that SCZ risk genes may converge into co-expression pathways which, in turn, may be associated with clinical phenotypes in patients with SCZ. Previous work in microarray post-mortem brain gene expression data shows that co-expression networks have biological plausibility for SCZ [2] . Methods Here, we used RNA sequencing data from the Lieber Institute for Brain Development (LIBD, N=343) [1] and the Common Mind Consortium (CMC, N=345) [3] to identify gene co-expression networks through Weighted Gene Co-expression Analysis. To detect gene modules in which PGC SCZ risk protein coding genes (n=300) were overrepresented, we computed hypergeometric tests and corrected the results for multiple comparisons (Bonferroni, number of modules=43). Then, we generated a Polygenic Co-expression Index (PCI) predicting gene co-expression based on a meta-analysis of LIBD and CMC. We replicated the PCI-co-expression association in BrainEAC, an independent post mortem microarray dataset (N=38). Finally, we studied a clinical cohort of drug-free patients with SCZ treated with olanzapine in monotherapy (N=49). We correlated patients’ PCI both with symptoms severity at the baseline assessment and treatment response (endpoint – baseline) in terms of positive, negative, and general PANSS domains. We Bonferroni-corrected results for the number of PANSS subscales (n=3). Results In LIBD, we discovered a single gene set enriched for SCZ risk loci (157 protein coding genes; PGC hits=12; corrected p=.0007), which was successfully replicated in CMC (empirical p Discussion These results corroborate the hypothesis that co-expression pathways are relevant to the neurobiology of SCZ and that a significant proportion of the risk genes is co-expressed in the dorsolateral prefrontal cortex. Furthermore, these findings provide preliminary evidence for the clinical relevance of this co-expression pathway and of the genetic variants associated with it.

Tardive dyskinesia in patients with schizophrenia treated with olanzapine - results from a 20-month, prospective, open study under naturalistic conditions

The objective of the study was to assess the prevalence and incidence of tardive dyskinesia in patients treated with olanzapine during the follow-up period of 20 months. It was a prospective, observational, non-interventional study under naturalistic conditions, without a control group. The evaluation of the severity and presence of tardive dyskinesia was performed with the Abnormal Involuntary Movement Scale and research criteria by Schooler and Kane. The study included 573 patients (woman 43,3%) with the diagnosis of schizophrenia (ICD-10), the mean age of 41.8 (± 12) years. The mean dose of olanzapine was 15.9 (± 4.2) mg. The prevalence of tardive dyskinesia was 16.4%. The cumulative incidence assessed in the group of 479 patients was 6.47%. The annual incidence was 3.9%. An increased risk of tardive dyskinesia was observed in smokers - RR of 1.99 (CI 0.88-4.49), those taking higher doses of olanzapine 1.57 (CI 0.91-2.7) and in those who used polytherapy: 3.55 (CI 1.43-8.82). Only in the case of polytherapy a multidimensional analysis confirmed that this factor had a significant influence on the risk of tardive dyskinesia (p=0.006). The study demonstrated high (16,4%) prevalence of tardive dyskinesia, and the annual incidence (3,9%) comparable to the results of a meta-analysis by Corell et al. In the case of olanzapine in monotherapy the annual incidence was lower (1.96%) but the use of antipsychotics in polytherapy more than tripled the risk of tardive dyskinesia.

Comparably high retention and low relapse rates in different subpopulations of bipolar patients in a German non-interventional study.

BackgroundAlthough a range of pharmacotherapeutical options are available for the treatment of bipolar disorder, patient non-adherence to prescribed treatment regimens and early treatment discontinuation remain among the primary obstacles to effective treatment. Therefore, this observational study assessed time on mood stabilizing medication and retention rates in patients with bipolar disorder (BD).MethodsIn an 18-month, prospective, multicenter, non-interventional study conducted in Germany 761 outpatients (≥18 years) with BD and on maintenance therapy were documented. For analysis, patients were stratified by baseline medication: monotherapy olanzapine (OM, N = 186), lithium (LM, N = 152), anticonvulsants (N = 216), other mood stabilizing medication (OMS, N = 44); combination therapy olanzapine/lithium (N = 47), olanzapine/anticonvulsant (N = 68), other combinations (OC, N = 48). Continuation on medication was assessed as retention rates with 95% confidence intervals. Time to discontinuation and relapse-free time were calculated by Kaplan-Meier analysis. A relapse was defined as increase to CGI-BP >3, worsening of CGI-BP by ≥2 points, hospitalization or death related to BD. A Cox regression was calculated for the discontinuation of mood stabilizing therapy (reference: OM). Logistic regression models with stepwise forward selection were used to explore possible predictors of maintenance of treatment and relapse.ResultsAfter 540 days (18 months), the overall retention rate of baseline medication was 87.7%, without notable differences between the cohorts. The overall mean time on mood stabilizing treatment was 444.7 days, with a range of 377.5 (OMS) to 481 (LM) by cohort. 74.0% of all patients were without relapse, with rates between the cohorts ranging from 58.4% (OC) to 80.2% (LM).ConclusionsRetention rates exceeded controlled trial results in all treatment cohorts, in addition to other explanations possibly reflecting that the physicians were expertly adapting treatment regimens to the individual patient’s disease characteristics and special needs.

PMH7 Aasenapine Versus Other Antipsychotics in Bipolar I Disorder: Indirect Comparisons at Twelve Weeks

Asenapine is a novel antipsychotic indicated for the treatment of moderate to severe manic episodes associated with bipolar I disorder. The clinical programme included one 12-week trial versus olanzapine in monotherapy and one 12-week adjunct therapy trial versus placebo. While no head-to-head data were available to compare asenapine with all atypical antipsychotics, the objective of this project was to provide comparative efficacy data of asenapine versus olanzapine, quetiapine and aripiprazole in both monotherapy and adjunct therapy using indirect comparison techniques. All twelve-week randomised controlled trials of olanzapine, quetiapine and aripiprazole conducted in monotherapy or in adjunct therapy were identified through a literature review. Five monotherapy studies were found, allowing the comparison of asenapine versus quetiapine and aripiprazole, with olanzapine and haloperidol as common references, using Bucher's method (Bucher et al., J Clin Epidemiol 1997). One twelve-week and four six-week placebo-controlled adjunctive therapy trials were identified, enabling the comparison of asenapine to olanzapine, quetiapine and aripiprazole through pairwise comparisons using placebo as a common reference. The outcomes used for comparison were the Young Mania Rating Scale (YMRS) change from baseline, YMRS response and remission rates. In monotherapy, the differences of mean YMRS change from baseline to week 12 between asenapine versus quetiapine and aripiprazole were 0.10 (p=0.959) and 1.76 (p=0.342), respectively. Relative risks for response and remission were close to one. In adjunct therapy, the differences of mean YMRS change from baseline to week 6 between asenapine versus olanzapine, quetiapine and aripiprazole were 0.63 (p=0.656), 0.10 (p=0.967) and -0.10 (p=0.946), respectively. Relative risks for response and remission were numerically in favour of asenapine but not statistically significant. The results of these indirect comparisons consistently showed comparable efficacy of asenapine versus the investigated atypical antipsychotics.

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

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. 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. 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). 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.