Olanzapine Long-acting Injection Research Articles

Acute Urinary Retention Associated with Olanzapine Long-acting Injection: A Case Report.

Acute Urinary Retention Associated with Olanzapine Long-acting Injection: A Case Report.

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data

There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence. We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis. We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries. LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines. None.

Clozapine in Combination With Olanzapine Long-Acting Injection: The Intersection of Treatment-Resistant Schizophrenia and Poor Medication Adherence-A Case Report.

Clozapine in Combination With Olanzapine Long-Acting Injection: The Intersection of Treatment-Resistant Schizophrenia and Poor Medication Adherence-A Case Report.

Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study.

Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse? To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder. Register-based cohort study including all Finnish residents aged 16-65 with a diagnosis of bipolar disorder from in-patient care, specialised out-patient care, sickness absence and disability pensions registers between 1996 and 2018, with a mean follow-up of 9.3 years (s.d. = 6.4). Antipsychotic and mood stabiliser use was modelled using the PRE2DUP method and risk for hospital admission for psychiatric and non-psychiatric reasons when using versus not using medications was estimated using within-individual Cox models. Among 60 045 individuals (56.4% female; mean age 41.7 years, s.d. = 15.8), the five medications associated with lowest risk of psychiatric admissions were olanzapine long-acting injection (LAI) (aHR = 0.54, 95% CI 0.37-0.80), haloperidol LAI (aHR = 0.62, 0.47-0.81), zuclopenthixol LAI (aHR = 0.66, 95% CI 0.52-0.85), lithium (aHR = 0.74, 95% CI 0.71-0.76) and clozapine (aHR = 0.75, 95% CI 0.64-0.87). Only ziprasidone (aHR = 1.26, 95% CI 1.07-1.49) was associated with a statistically higher risk. For non-psychiatric (somatic) admissions, only lithium (aHR = 0.77, 95% CI 0.74-0.81) and carbamazepine (aHR = 0.91, 95% CI 0.85-0.97) were associated with significantly reduced risk, whereas pregabalin, gabapentin and several oral antipsychotics, including quetiapine, were associated with an increased risk. Results for a subcohort of first-episode patients (26 395 individuals, 54.9% female; mean age 38.2 years, s.d. = 13.0) were in line with those of the total cohort. Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions.

Post-injection syndrome and olanzapine long-acting injection in patients with schizophrenia: A case series

Pamoate salt of atypical antipsychotic Olanzapine in long-acting injection depot formulation (OLAI) is often used in patients with schizophrenia having poor compliance. This depots formulation having a cluster of adverse events characterized by post-injection delirium/sedation syndrome (PDSS). Here, we present three cases of different age group, different gender suffering from Schizophrenia of varied duration of illness who developed PDSS after receiving OLAI, how they were identified and promptly managed with early intervention. PDSS noted in approximately 0.07% of the injections, in 1.3% of patients. Symptoms such as sedation, delirium, extrapyramidal symptoms, ataxia, autonomic dysfunction, aggression, and speech impairment were reported, onset was immediate to 3–5 h post-injection, patients recovered within 2–72 h. No such risk factors could be identified in any of the cases. PDSS following OLAI occurs when there is accidental intravascular release of high dose of olanzapine. The importance of post-injection syndrome in the above cases lies in the fact that following administration of OLAI a 3–4-h observation period in a health-care facility in the presence of an appropriate qualified personnel is of utmost importance. Furthermore, one should rule out other causes of acute sedation in such patients before establishing the diagnosis of PDSS. There is no specific antidote for olanzapine and almost all such patients improve with conservative and supportive treatment.

Switch from Olanzapine Long-Acting Injectable to its Oral Equivalent during COVID-19 Pandemic: a Real World Observational Study

Schizophrenia is a psychiatric condition with chronic evolution, one of the most disabling diseases. The main cause for the disease’s progression is considered to be the lack of compliance with the treatment. Long-acting injectable antipsychotics (LAIs) are an important treatment option for patients with schizophrenia. Olanzapine long-acting injection (OLZ-LAI) is a pamoate monohydrate salt of olanzapine that is administered by deep intramuscular gluteal injection. The aim of this paper is to report the effects of a sudden and unplanned switch from olanzapine long-acting injectable to oral olanzapine in remitted patients with schizophrenia due to restrictions caused by the COVID-19 pandemic. An observational study conducted in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania between April 2020 and March 2021. 27 patients with OLZ-LAI were entered into the study. Of 27 cases, 21 patients preferred to be switched to oral olanzapine (77.77%). Only 6 patients continued with the long-acting formulation. The main reason for the initiation of olanzapine pamoate in all the patients was non-adherence to oral medication (80.95%), and the mean age of starting LAI olanzapine was 36.42 years (SD ± 10.09). Within the following 12 months after switching from olanzapine LAI to OA, 15 patients (71.42%) relapsed, and 12 were admitted to the emergency psychiatric unit. The COVID-19 pandemic has brought multiple disservices to current medical practice. Sudden and unplanned switch from olanzapine long-acting formulation to oral olanzapine was followed by the high rate of relapse in remitted schizophrenia.

Olanzapine long-acting injection, discontinuation rates and reasons for discontinuation: 10 years' experience at a UK high-secure hospital.

Background:Olanzapine pamoate has been shown to be an effective second-generation long-acting injection. Its popularity has possibly been adversely affected by the rare incidence of post-injection syndrome (PIS) and the associated requirement to monitor for 3 h after each injection.Objective:This study aimed to collect and present data on the use of olanzapine long-acting injection (OLAI) over a 10-year period in a high-security forensic hospital in South East England.Design:This was a non-interventional retrospective study collecting information from anonymised electronic patient and prescription records. As per hospital Trust guidelines, patient consent to access of hospital records was presumed unless explicitly withdrawn.Method:All patients prescribed OLAI between the years 2009 and 2019 were identified. Data collected included date that OLAI was started, stopped, dose range, side effects and concomitant medication.Results:Of 88 patients who were started OLAI, 45 (51%) continued at month 24. At 60 months, 22 of 70 (31%) patients for whom data were available continued with OLAI. Over 60% of continuers were on higher than recommended doses. Of almost 5000 injections administered, there was 1 episode of PIS.Conclusion:OLAI is an effective treatment for schizophrenia and schizoaffective disorder, especially when used in patients have been able to tolerate the drug and were stabilised on it for 24 months. In over half the patients who continued OLAI, the doses were higher than that recommended by the manufacturer. The incidence of PIS in this study was very low in comparison with other studies.Registration code:2049

Evaluating adult forensic staff knowledge of olanzapine long-acting injection post injection syndrome: a service improvement project

AimsPost injection syndrome (PIS) is a serious complication that can occur after Olanzapine Long Acting Injection (LAI). It can occur without any derangement in physical observations. It is important that patients are monitored appropriately following administration of Olanzapine LAI to ensure that symptoms of PIS are appropriately identified and managed. This project aimed to evaluate the current level of knowledge about PIS in two staff groups within an Adult Forensic Service – in-patient nursing staff and junior doctors and advanced practitioners (APs) providing medical cover to inpatient wards.MethodElectronic surveys evaluating knowledge about the symptoms of PIS, monitoring requirements and management of possible PIS were circulated to inpatient nursing staff, junior doctors and APs working within an Adult Forensic Service in the North West of England.Result1) Nursing staff knowledge – 26 nursing staff completed the survey. 4.5% of nurses correctly identified all symptoms of PIS and 72.7% believed that tachycardia or hypotension occur in PIS. 22.7% of nurses identified the correct management plan if a patient feels unwell following Olanzapine LAI. 40.9% would only request a medical review if physical observations were abnormal. 2) Junior doctor and AP knowledge – 6 doctors and 6 advanced practitioners completed the survey. 17% of doctors and APs correctly identified all symptoms of PIS. 50% believed hypotension or tachycardia were symptoms of PIS. 25% of doctors and APs identified correct management of PIS and 16.7% believed that the patient should be managed on the psychiatric ward unless physical observations became abnormal.ConclusionLevels of knowledge about the symptoms and management of PIS are low within this Adult Forensic Service. Knowledge of PIS and management of suspected PIS needs to be improved in nursing staff, junior doctors and advanced practitioners to ensure correct identification and safe management. In response to these findings, a care plan for monitoring of patients after Olanzapine LAI was developed. This included a structured monitoring proforma for completion post depot administration and instructions for managing suspected PIS. This care plan is kept in the front of the drug chart of all patients prescribed Olanzapine LAI. One-page educational summaries on PIS were written and circulated to nursing staff, junior doctors and APs. Information on Olanzapine LAI use and PIS were included in junior doctor induction materials and on-call handbook, to improve trainee awareness and knowledge.

Comparison of hospitalizations in patients on first generation versus second generation long acting injectable (LAI) antipsychotics

AimsThere is limited data on the comparison of efficacy between first and second antipsychotic LAIs. One good indicator of efficacy is the rates of hospitalization. Some studies have shown that second generation depot antipsychotics, significantly reduce hospitalizations as compared to conventional depots.Our aim was to compare hospitalizations in patients on first and second generation LAI antipsychotics.MethodA retrospective observational study was done by reviewing the records of all the depot clinics in South Essex, United Kingdom. A list of patients enrolled and receiving LAI antipsychotics was obtained from the 6 depot clinics. Data were collected by going through the electronic records of the patients on the depot clinic lists and taking down the demographics, diagnosis and the hospital admissions. Other variables like comorbid drug abuse were also recorded.ResultAmongst a total of 346 patients 223 (64 %) were males and 123 (36%) were females. Average age was 50.3 (range 21 to 88 years) and 290 (83%) patients were single. An overwhelming majority of patients 299 (87 %) were not in employment. Regarding the diagnosis, the majority, 237 patients were diagnosed with Paranoid Schizophrenia, 49 patients were diagnosed with Schizoaffective disorder, 38 patients were diagnosed with Bipolar affective disorder, 20 patients had a diagnosis of Delusional disorder and only 2 patients had a primary diagnosis of Mental and Behavioral disorders due to substance abuse. Of the total 346 only 17 patients were on a Community treatment Order.Risperidone was the most commonly used second generation LAI at 26%,Aripiprazole in 10% and Paliperidone was used in 5% patients. Olanzapine LAI was only used in 2 patients. Amongst first generation LAIs Zuclopenthixol, Fluclopentixol were both used in 24%, and Haloperidol in 10% patients. 21 % of patients were reported to be actively abusing drugs.65 (32.6%) of the total 200 patients on Ist Generation LAIs had hospital admissions55 (39.8%) of the total 138 patients on 2nd Generation LAIs had hospital admissionsThis difference was not statistically significant (Z test)- P value of 0.082427ConclusionThe results in our observational study are equivocal, both LAIs providing equitable decrease in the hospital admissions albeit with a slightly favourable outcome (not statistically significant though) attributable to the first generation LAIs. There was a high incidence of unemployment and drug abuse in our cohort of patients, thus targeted interventions can be established in rehabilitation of such individuals.

One-year mirror-image study of the impact of olanzapine long-acting injection on healthcare resource utilization and costs in severe schizophrenia

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of −0.47 and −0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia.

Intraindividual and Interindividual Variability of Olanzapine Trough Concentrations in Patients Treated With the Long-Acting Injectable Formulation.

A long-acting injectable (LAI) formulation of olanzapine has been developed as an alternative to oral regimens. A therapeutic range of 20 to 80 ng/mL for oral olanzapine trough concentrations has been proposed. Here, we sought to investigate the intraindividual and interindividual variability of olanzapine concentrations with time in patients on maintenance therapy with the LAI formulation carried out in the routine clinical practice. To address this issue, we carried out a retrospective analysis of therapeutic drug monitoring of olanzapine concentrations in 21 schizophrenic patients on maintenance LAI olanzapine. Drug concentrations were correlated with LAI olanzapine doses, duration of treatment, and main clinical characteristics. Fifty percent of the patients had olanzapine trough concentrations lower than 20 ng/mL. Only drug doses significantly correlated with olanzapine exposure. Mean interindividual and intraindividual coefficients of variations of olanzapine concentrations were 56% (range, 21%-97%) and 34% (range, 15%-69%), respectively. We have documented that, in a real-life setting, a large proportion of patients treated with olanzapine LAI had drug trough concentrations of less than 20 ng/mL; wide intraindividual and interindividual variability of olanzapine concentrations has been also observed. Our results could provide the rationale for the design of larger prospective, concentration-controlled clinical trials specifically designed with the goal to identify ad hoc therapeutic ranges of drug concentrations for olanzapine LAI.

Postinjection delirium/sedation syndrome in patients with schizophrenia receiving olanzapine long-acting injection: results from a large observational study.

BackgroundPostinjection delirium/sedation syndrome (PDSS) has been reported uncommonly during treatment with olanzapine long-acting injection (LAI), a sustained-release formulation of olanzapine.AimsThe primary aim of the study was to estimate the incidence per injection and per patient of PDSS events in adult patients with schizophrenia who were receiving olanzapine LAI in real-world clinical practice. Secondary aims were to further characterise the clinical presentation of PDSS events, to identify potential risk factors associated with PDSS events and to characterise hospitalisations at baseline and post-baseline.MethodA prospective observational study of adult patients with schizophrenia receiving olanzapine LAI from 24 countries. Data were collected on patient characteristics, olanzapine LAI treatment and any adverse events (AEs). All AEs were reviewed and adjudicated for PDSS using predetermined criteria.ResultsThere were 46 confirmed PDSS events (0.044% of the 103 505 injections) in 45 patients (1.17% of the 3858 patients). Based on 45 confirmed events with time-to-onset information, 91.1% (n=41) occurred within 1 h of injection. Time-to-recovery from the event was within 72 h for 95.6% of patients (range 6 h to 11 days). Risk factors for PDSS (per-injection) included high dose (odds ratio (OR)high/low=3.95; P=0.006) and male gender (ORfemale/male=0.42; P=0.017).ConclusionsResults of this study confirm previously reported PDSS rates, time to onset and recovery, and the severity of PDSS events, and suggest that higher doses and male gender are potential risk factors associated with PDSS.Declaration of interestAll authors are full-time employees and hold stock/stock options in Eli Lilly, which funded this study. This post-authorisation safety study (PASS) was proposed by Eli Lilly when submitting the original marketing authorisation application for olanzapine LAI in 2007. The protocol and final study report for this European Union regulatory commitment are publicly accessible via the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) European Union PASS Register (www.encepp.eu/encepp/viewResource.htm?id=16847). The current manuscript describes the results within the final study report.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Safety concerns associated with second-generation antipsychotic long-acting injection treatment. A systematic update.

Background It has been recently suggested that second-generation antipsychotic long-acting injection (SGA-LAIs) are underutilized in clinical practice, despite that their costs significantly impact on national health system budgets. Hence, an updated analysis of safety data shown by SGA-LAIs may contribute to clarify their role in clinical practice. Materials and methods English-language, peer-reviewed articles reporting updated, primary findings on the SGA-LAI safety were identified (updated through an electronic search of five databases - PubMed, EMBASE, PsycInfo, DARE and the Cochrane Library). Results The articles reviewed suggest that the most frequent treatment emergent adverse events (TEAEs) associated with aripiprazole long-acting injection (ARI-LAI) are psychotic symptoms, extrapyramidal symptoms (EPS) and weight gain. Data on olanzapine long-acting injection (OLA-LAI)-associated TEAEs highlight the risk of psychosis, metabolic disturbances and hyperprolactinemia. Four-hundred and forty cases of post-injection delirium/sedation syndrome (PDSS) have also been recorded. Although not reported in reviewed studies, the risk of impulse-control problem and drug reaction with eosinophilia and systemic symptoms (DRESS) ARI- and OLA-associated, respectively, must not be underestimated. With regards paliperidone palmitate 1-month formulation (PP1), the high incidence of clinically relevant weight gain and hyperprolactinemia are both findings of concern. Reviewed data also confirm that the leading cause of death in risperidone long-acting injection (RIS-LAI) clinical trials is suicide. The new 3-month paliperidone palmitate formulation, risperidone sustained release 1-month formulation (RIS-SR1), aripiprazole lauroxil (ARI-LXL) are still lacking exhaustive safety data. Conclusion The risk of specific TEAEs associated with all SGA-LAIs confirms SGA-LAIs do not offer advantages in safety compared with FGA-LAIs or oral antipsychotics and, especially, in early-phase schizophrenia patients. Implementing non pharmacological intervention and strategies can be effective for people with schizophrenia and bipolar disorder who adhere poorly to medication regimens.

Real-world effectiveness of antipsychotic treatments among patients with schizophrenia and affective symptoms

IntroductionThe clinical distinction between schizophrenia and affective psychoses is often not clear-cut, and very little is known about the effectiveness of treatments among patients having both schizophrenia and affective symptoms.ObjectivesTo study the comparative real-world effectiveness of antipsychotic treatments among patients having schizophrenia and affective symptoms.MethodsWe studied the risk of all-cause rehospitalization during use of specific antipsychotics during 1996–2012 among all patients who had been previously hospitalized with both schizophrenia and mood disorder diagnoses in Finland since 1987 (n = 28,015). We linked nation-wide databases on hospitalization, mortality, and filled prescriptions. The primary analysis was within-individual analysis, in which each individual was used as his/her own control to eliminate selection bias. The effect of concomitant psychotropic medications, and the temporal orders of exposure and non-exposure periods were adjusted.ResultsWhen 22 specific antipsychotic treatments were compared with the most frequently used antipsychotic quetiapine, the lowest rehospitalization risks were observed during the treatment periods of olanzapine long-acting injection (LAI) (HR: 0.52; 95% CI: 0.34–0.80), risperidone LAI (0.67; 0.56–0.81), and clozapine (0.68; 0.63–0.74). The worst outcome was observed for periciazine (1.19; 0.96–1.48) and no antipsychotic use (1.09; 1.04–1.13).ConclusionsOlanzapine LAI, risperidone LAI, and clozapine use are associated with the lowest risk of rehospitalization among patients with schizophrenia and affective symptoms.Disclosure of interestJari Tiihonen has served as a consultant to The Finnish Medicines Agency Fimea, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen-Cilag, Lundbeck, Organon, and Finnish Medicines Agency he has received fees for giving expert testimony to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka and Pfizer lecture fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novartis, Otsuka, Pfizer and grants from Stanley Foundation and Sigrid Jusélius Foundation. Tiihonen is a member of advisory boards for AstraZeneca, Eli Lilly, Janssen-Cilag, and Otsuka, and has research collaboration with Lilly and Janssen. Markku Lähteenvuo is a major shareholder and board member at Genomi Solutions ltd, a Finnish based bioinformatics company. He has also received research grants or awards from Boehringer-Ingelheim, and is working as a coordinator for a research project funded by the Stanley Foundation. Fabian Hoti and Pia Vattulainen are employed by EPID Research, which is a contract research organization that performs commissioned pharmacoepidemiological studies and thus its employees have been and currently are working in collaboration with several pharmaceutical companies. Antti Tanskanen and Heidi Taipale have participated in research projects funded by Janssen with grants paid to the Karolinska Institutet.

Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

BackgroundThe objective of the present analysis is to determine the impact of the 3-hour observation period for olanzapine long-acting injection (LAI) on patient satisfaction and well-being by comparing data collected before and after its implementation.MethodsThis is a post hoc analysis of patients treated with olanzapine LAI in 1) a 6-month fixed-dose randomized controlled trial and/or 2) a 6-year open-label safety study. This analysis was limited to patients with schizophrenia who were treated with olanzapine LAI consistent with the approved indication and dosing recommendations of the European Union Summary of Product Characteristics (N=966). Of the 966 patients, the analysis further focused only on those patients who received both 1) at least one injection before the implementation of the 3-hour observation period and 2) at least one injection after implementation of the 3-hour observation period (N=487). Patient satisfaction was assessed with the three-item Patient Satisfaction with Medication Questionnaire-Modified. Responses were averaged across all postbaseline visits occurring before (ie, without) the implementation of the 3-hour observation period and across all postbaseline visits occurring after (ie, with) the implementation of the 3-hour observation period. In addition, the rate of postinjection delirium/sedation syndrome events was calculated.ResultsThere was no meaningful change after implementation of the 3-hour observation period in satisfaction (before: mean [SD] =4.0 [1.02] and after: mean [SD] =4.1 [0.82]), preference for olanzapine LAI over oral medication (before: mean [SD] =4.0 [0.90] and after: mean [SD] =4.1 [0.77]), or ratings of satisfaction regarding side effects (before: mean [SD] =1.9 [0.79] and after: mean [SD] =1.8 [0.60]). For the total population (N=966), postinjection delirium/sedation syndrome occurred in 26 (0.07%) of 38,010 injections.ConclusionFor patients with schizophrenia receiving treatment with olanzapine LAI, the 3-hour observation period had no impact on their satisfaction with the medication or on their subjective well-being.

Comparaison des bénéfices médico-économiques des antipsychotiques dans la prise en charge de la schizophrénie en France

IntroductionThe course of schizophrenia can vary widely, and patients experience remission phases alternating with relapse episodes, which generally lead to hospitalisation and have a significant impact on the burden of disease. The prevalence of schizophrenia in France is estimated to be approximately 600,000 people, with an incidence of 10,000 new patients per year. Patients with schizophrenia represent the largest group of hospitalised patients in French public institutions and specialised centres, and the French authorities recognise that the management of schizophrenia is a major public health concern. The Haute Autorité de Santé (HAS) and most of the evidence-based guidelines for the maintenance treatment of schizophrenia recommend long-acting injectable (LAI) antipsychotics to be used predominantly in the prevention of relapse for non-compliant patients; however, in clinical practice, the use of LAIs remains low. ObjectiveThis analysis aimed to estimate and to compare the cost-effectiveness of the most common antipsychotic strategies in France in the management of schizophrenia. MethodsA Markov model was developed to simulate the progression of a cohort of patients with schizophrenia through four health states (stable treated, stable non-treated, relapse and death) and considered up to three lines of treatment to account for changes in treatment management. Antipsychotics including aripiprazole LAI (ALAI), olanzapine LAI (OLAI), paliperidone LAI (PLAI), risperidone LAI (RLAI), haloperidol decanoate (HD) and oral olanzapine (OO) were compared in terms of costs and clinical outcomes. Thus, costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over five years based on three-month cycles from a French health insurance perspective with a discount rate of 4 %. Patients were considered to be stabilised after clinical decompensation and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on French real-life data in order to capture adherence effects. Safety and utility data were derived from international publications. Additionally costs were retrieved from French health insurance databases and publications. Robustness of results was assessed through deterministic and probabilistic sensitivity analyses. ResultsFirst and second generations of LAIs were found to have similar costs over five years; i.e. approximately € 55,000, except for PLAI which was associated with a discounted cost of € 50,880. Oral antipsychotics were found to be less costly (i.e. OO cost € 50,379 after five years) but associated with a lower number of QALYs gained and relapse avoided. PLAI and RLAI were associated with the greatest number of QALYs gained; i.e. PLAI dominated ALAI, OLAI and HD and was associated with an incremental costs-effectiveness ratio (ICER) of € 2411 per QALY gained versus OO. Finally, PLAI and OLAI were associated with the lowest number of relapses; i.e. PLAI dominated RLAI, ALAI and HLAI and was associated with an ICER of € 1782 per avoided relapse compared to OO. OO and HD were found to have led to the highest number of relapses. ConclusionThis analysis, to the best of our knowledge, is the first of its kind to assess the cost-effectiveness of antipsychotics based on French observational data. PLAI was associated with the highest probability of being the optimal treatment from the French health insurance perspective.

Intramuscular maintenance treatment with ultra-high-dose long-acting injectable aripiprazole in an elderly patient suffering from chronic refractory schizophrenia: A case report

Long-acting injectable (LAI) aripiprazole is increasingly appreciated in the course of a maintenance treatment of schizophrenia due to efficacy in delaying – and decreasing relapse, and low rates of feared side effects. In line with the prescribing information, the maximal starting – as well as maintenance dose was restricted to 400 mg following a 26-day interval between the single doses.We present a 72-year-old female inpatient (66 kg) with an acute exacerbation of chronic refractory schizophrenia, exhibiting primarily positive symptoms including excessive persecutory delusions, self-care deficit, poor insight and insufficient adherence to continuous intake of oral medication. Since she developed a post-injection syndrome after an accidental intravascular administration of olanzapine LAI 405 mg, the antipsychotic treatment was switched to aripiprazole LAI 300 mg once monthly. Due to insufficient clinical response, aripiprazole LAI was gradually increased up to 1200 mg per month under continuous plasma level monitoring. Here, 2 single injections of aripiprazole LAI 300 mg were delivered into both gluteal muscles concurrently, every 14 days.Consequently, we observed a clinically meaningful improvement (a total-score reduction from 111 to 75 on the Positive and Negative Syndrome Scale), as well as no objectifiable side effects, assessed by “The Dosage Record Treatment Emergent Symptom Scale” and “The Barnes Akathisia Rating Scale”, despite multi-morbidity and rather advanced age of the patient.Our safe experience with applying the almost threefold higher monthly dose over 12 weeks may encourage researchers to further investigate the efficacy, tolerability as well as handling of highly dosed aripiprazole LAI in refractory schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Baseline characteristics and hospitalizations in patients with schizophrenia receiving olanzapine long-acting injection: an interim analysis from a non-interventional, prospective observational safety study.

BackgroundDepot antipsychotics are a treatment option for medication nonadherence in patients with schizophrenia. Nonadherence can lead to increased relapse and hospitalization rates. This article reports hospitalization data before and after initiation of olanzapine long-acting injection (LAI), a depot antipsychotic.MethodsData were assessed from an ongoing, multinational, prospective, observational post-authorisation safety study being conducted to evaluate post-injection delirium/sedation syndrome (PDSS), an adverse reaction that can occur following injection of olanzapine LAI. Eligible patients were aged ≥18 years, diagnosed with schizophrenia, were prescribed olanzapine LAI, and lived outside the United States. Psychiatric hospitalization and medication data were collected retrospectively for the 6-month period before study entry and prospectively throughout the study. Paired t-tests and McNemar’s tests were used to assess changes in hospitalization incidence and duration. Stepwise Cox proportional hazards models assessed factors associated with hospitalizations. Analyses were based on data from the first 3 years of the continuously enrolling study (N = 668).ResultsThe average duration of olanzapine LAI exposure for all patients was 0.768 years. Of the 529 patients who received at least 1 injection of olanzapine LAI and were not hospitalized at study entry, 8.1 % had at least 1 subsequent psychiatric hospitalization with a mean duration of 2.0 days. Of the 288 patients who had a >6-month follow-up, 8.3 % had at least 1 post-baseline psychiatric hospitalization with a mean duration of 2.3 days. The incidence of hospitalizations in the 6-month period after treatment was significantly lower than that in the 6-month period prior to treatment (8.3 vs 32.6 %, respectively; P < 0.001). Furthermore, mean hospitalization duration decreased from 11.5 days in the 6-month period before treatment to 2.3 days in the 6-month period after treatment (P < 0.001). Psychiatric hospitalization in the prior 12 months (P < 0.0001) and recreational drug use within 24 h of baseline visit (P = 0.015) were identified as potential predictors of time to first psychiatric hospitalization after beginning to take olanzapine LAI. At the time of interim analysis, 5 PDSS events had occurred, which was too few for a full analysis of those events.ConclusionsResults indicate a significant reduction in the incidence and days of hospitalization from the 6-month period before to the 6-month period after olanzapine LAI initiation, which suggests reduced relapse and hospitalization during treatment. Results should be interpreted with caution due to the observational nature of the study and use of retrospective baseline data.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0669-5) contains supplementary material, which is available to authorized users.

A 6-year open-label study of the efficacy and safety of olanzapine long-acting injection in patients with schizophrenia: a post hoc analysis based on the European label recommendation.

PurposeTo assess the long-term efficacy and safety of olanzapine long-acting injection (LAI) in the treatment of schizophrenia, focusing on clinical trial data consistent with the approved indication and dosing recommendations in the European label and which forms the basis for treatment decisions made by clinicians in daily clinical practice.Patients and methodsThis was a post hoc analysis of a 6-year open-label study of olanzapine LAI in patients (male or female, 18–75 years old) with schizophrenia entering this study following feeder studies of olanzapine LAI. Patients were flexibly dosed (45–405 mg, 2- to 4-week intervals), but those receiving oral olanzapine supplementation whose total olanzapine dose was >20 mg/day equivalent were excluded from this post hoc analysis.ResultsData from 669 patients were analyzed (44.5% completed). Positive and Negative Syndrome Scale total scores did not change significantly from baseline to endpoint; Clinical Global Impression-Severity scores improved significantly. Mean weight change was +2.19 kg (P<0.001), with 40.8% of patients experiencing ≥7% weight gain. There were 24 occurrences of post-injection delirium/sedation syndrome (PDSS).ConclusionOlanzapine LAI appeared to be effective in the long-term maintenance of schizophrenia, and the safety profile was consistent with that of oral olanzapine, except for injection-related events and PDSS events.

Olanzapine long-acting injection: a review of first experiences of post-injection delirium/sedation syndrome in routine clinical practice.

BackgroundOlanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use.MethodsCases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014).ResultsA total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) were sedation (61%), confusion (56%), dysarthria (54%), somnolence (46%), dizziness (45%) and disorientation (35%). Overall, PDSS occurred with approximately 0.07% of injections and in 0.46–1.03% of patients (reporting and incidence rates from spontaneous reports and post-marketing safety studies, respectively).ConclusionsThe PDSS events reported during routine clinical use of olanzapine LAI are generally similar in incidence and presentation to those reported in clinical trials. Caution should be applied when interpreting spontaneously reported rates of adverse events, however, due to potential under-reporting. Implemented risk-minimisation activities may contribute substantially to the identification and appropriate management of patients with PDSS in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0450-9) contains supplementary material, which is available to authorized users.