Olanzapine Long-acting Injection Research Articles

Efficacy of olanzapine long-acting injection in patients with acutely exacerbated schizophrenia: an insight from effect size comparison with historical oral data

BackgroundTo treat acute schizophrenia, a long-acting injectable antipsychotic needs a rapid onset of action and therapeutic profile similar to that of oral agents. The present post-hoc analyses compared results from a randomized, double-blind, placebo-controlled trial of olanzapine long-acting injection (LAI) for acute schizophrenia with those observed in similarly designed trials of oral olanzapine.MethodsSix-week results from the olanzapine LAI study (N = 404) were compared with those of 3 oral studies (study 1: olanzapine vs. haloperidol vs. placebo [N = 335]; study 2: olanzapine vs. haloperidol vs. low-dose olanzapine [N = 431]; study 3: olanzapine vs. placebo vs. low-dose olanzapine [N = 152]). All patients had baseline Brief Psychiatric Rating Scale (BPRS) scores ≥24 (0–6 scale). Six-week effect sizes were calculated. Efficacy onset, pharmacokinetics, discontinuations, weight gain, and extrapyramidal symptoms were also assessed.ResultsAt 6 weeks, mean BPRS scores decreased by 14 to 15 points for olanzapine LAI (405 mg/4 weeks, 210 or 300 mg/2 weeks), by 8 to 16 for oral olanzapine (10 ± 2.5 or 15 ± 2.5 mg/day), and by 12 to 13 for haloperidol (15 ± 5 mg/day). For those same dose groups, effect sizes vs. placebo for the BPRS were 0.7 to 0.8 for olanzapine LAI, 0.5 to 0.7 for oral olanzapine, and 0.6 for haloperidol. The first statistically significant separation from placebo on the BPRS occurred at 3 days for the olanzapine LAI groups and at 1 week for oral olanzapine and haloperidol (15 ± 5 mg/day) in oral study 1 although as late as week 6 for the 10-mg/day olanzapine dose in oral study 3. Olanzapine concentrations were similar across studies. Weight gain ≥7% of baseline occurred in up to 35% of olanzapine LAI and oral patients versus up to 12% of haloperidol and placebo patients. Extrapyramidal symptoms were lowest in the olanzapine LAI groups and significantly greater in the haloperidol groups. No post-injection delirium/sedation syndrome events occurred in the olanzapine LAI study.ConclusionsPatients treated acutely with olanzapine LAI showed a similar pattern of improvement to that seen historically with oral olanzapine. With the exception of injection-related adverse events, the efficacy and tolerability profile of olanzapine LAI is similar to oral olanzapine.Trial registrationClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00088478; ClinicalStudyResults.org ID; URL: http://www.clinicalstudyresults.org/: 917, 978, 982, and 5984.

Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons.

BackgroundLittle is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia.MethodsIndirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication’s effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study) with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates.ResultsComparison of olanzapine long-acting injection data (931 patients) with the pooled data from the nine risperidone long-acting injection studies (3950 patients) provided almost identical 12-month treatment-completion rates (72.7% versus 72.4%; P = 0.87). When the two most similar studies were compared, the 12-month completion rate for olanzapine long-acting injection was significantly higher than for risperidone long-acting injection (81.3% versus 47.0%; P < 0.001). However, any conclusions drawn from this comparison may be limited by differences in the studies’ geographic catchment areas.ConclusionUsing treatment-completion rates as a proxy measure of medication effectiveness, olanzapine long-acting injection did not differ significantly from risperidone long-acting injection when including all eligible studies. However, the findings of this exploratory analysis should be interpreted with caution, considering the methodological limitations of these indirect, cross-study comparisons.

Olanzapine long-acting injection: insights from an early case series in the UK

Olanzapine long-acting injection depot (OLAI) has been licensed in the UK since 2008. As a result of the recognition during clinical trials that in 0.07% of injections there may be inadvertent intravenous administration leading to post-injection delirium/sedation syndrome (PDSS), the licence mandates a 3 h observation after each injection and accompaniment of the patient to their final destination. The administration of OLAI may thus necessitate organization of local service provisions. We report on how a single healthcare facility in Northern Ireland has treated three initial patients and present a brief case series on these patients and their clinical outcomes. In the first three patients with schizophrenia to receive OLAI, the clinical notes were retrospectively examined to provide clinical data. All three patients had acceptable clinical outcomes showing sustained clinical improvement and have continued on OLAI for over 1 year. Observation has been undertaken within an existing daycare unit staffed by nursing staff and occupational therapists for 3 h after each injection. No issues have emerged from the use of this service that has also provided educational and psycho-educational programmes for the patients. No cases of post-injection delirium/sedation syndrome were reported. There have been no additional cost implications. In patients for whom OLAI may be clinically indicated, the utilization of an existing service to provide the 3 h of observation after each injection may represent a solution with a cost-neutral outcome.

Poster #207 LONG-TERM FUNCTIONAL IMPROVEMENTS IN THE 2-YEAR TREATMENT OF SCHIZOPHRENIA OUTPATIENTS WITH OLANZAPINE LONG-ACTING INJECTION

Background: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI), and whether observed changes differ from those seen with oral olanzapine. Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264) with daily oral olanzapine (10 mg/day; n=260). Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score) from 64.0–70.8 (P0.001). Patients on oral olanzapine also increased their level of functioning from 62.1–70.1 (P0.001). At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P0.05). The figures for oral olanzapine were 14.2% and 24.5%, respectively (P0.001). Results did not significantly differ between olanzapine-LAI and oral olanzapine. Conclusion: In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time.

Effects of olanzapine long-acting injection on levels of functioning among acutely ill patients with schizophrenia

Objective:To assess the effects of olanzapine long-acting injection (olanzapine-LAI) on levels of functioning in acutely ill patients with schizophrenia.Research design and methods:During this 8-week randomized, double-blind, placebo-controlled trial, 404 inpatients were randomized to four treatment arms (olanzapine-LAI 210 mg/2 weeks = 106; olanzapine-LAI 300 mg/2 weeks = 100; olanzapine-LAI 405 mg/4 weeks = 100; placebo = 98). Also, data from the three active dosing arms were combined and compared to placebo data.Clinical trial registration:NCT00088478Main outcome measures:The treatment group comparison of mean change from baseline to endpoint in the total score and four subdomains of the Heinrichs–Carpenter Quality of Life Scale (QLS) and in the 2 summary scores and 8 subscale scores of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were assessed using an ANOVA model.Results:All three olanzapine-LAI treatment groups and the combined olanzapine-LAI group were superior to placebo on the QLS total score (all p-values < 0.01) and the Intrapsychic Foundations subdomain (all p-values < 0.02). Olanzapine-LAI 210 mg/2 weeks (p < 0.001), 300 mg/2 weeks (p = 0.006), and the combined olanzapine-LAI group (p = 0.003) were superior to placebo on the Interpersonal Relations subdomain. The 300 mg/2 weeks group (p = 0.027) and the combined olanzapine-LAI group (p = 0.014) were also superior to placebo on the Instrumental Role subdomain. For the SF-36, the 300 mg/2 weeks and 405 mg/4 weeks olanzapine-LAI groups and the combined olanzapine-LAI group were superior to placebo on the Mental component score (all p-values < 0.05). Each olanzapine-LAI group and the combined group were superior on the Mental Health scale (all p-values < 0.05). Significant negative correlations between PANSS scores and measures of functioning indicate that as symptoms decreased, functioning increased.Conclusion:These results suggest that olanzapine-LAI may improve level of functioning in acutely ill patients with schizophrenia within 8 weeks of initiating treatment.

Development of a Medication Monitoring System for an Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT) Team

Purpose: The primary goal was to improve medication management oversight for a severely mentally ill (SMI) community-based population by developing a medication monitoring system based on current guidelines to optimize pharmacotherapy and minimize potential medication-related adverse effects. The secondary goal was improvement in coordination of care between healthcare providers.&#x0D; Methods: Guidelines for medication used for psychiatric indications were reviewed. A database of medication for psychiatric indications with monitoring recommendation was developed.&#x0D; Results: Medication regimens for 68 members of the Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT) program qualified for review. Fourteen medications, carbamazepine, chlorpromazine, clozapine, fluphenazine and fluphenazine long-acting injections (LAI), haloperidol and haloperidol LAI, lithium, lurasidone, olanzapine, paliperidone and paliperidone LAI, perphenazine, quetiapine, risperidone and risperidone LAI, valproic acid/divalproex, and ziprasidone, were identified. In total, 111 medications are used on a monthly basis. Each member receives more than one medication qualifying for review. Additional monitoring parameters that were evaluated included changes in laboratory orders for members with insulin-dependent diabetes. Annual lipid panels were changed to every 6 months, if applicable.&#x0D; Conclusions and Future Directions: This medication monitoring program was developed to help ensure IMPACT members receive the most effective care and minimize potential medication-related adverse effects. The secondary goal was to improve coordination of care. Medication monitoring will be added as a continuous quality assurance measure. Lab results will be reviewed at least monthly. The medication monitoring program will be evaluated annually.&#x0D; &#x0D; Type: Student Project

PMH3 Olanzapine Long-Acting Injection for Schizophrenia: An Evaluation of Patient Functioning During 24 Weeks of Maintenance Therapy

PMH3 Olanzapine Long-Acting Injection for Schizophrenia: An Evaluation of Patient Functioning During 24 Weeks of Maintenance Therapy

PMH12 Risk of Relapse and Hospitalization in the 2-Year Open-Label Treatment of Outpatients with Schizophrenia Randomized to Olanzapine Long-Acting Injection or Oral Olanzapine

PMH12 Risk of Relapse and Hospitalization in the 2-Year Open-Label Treatment of Outpatients with Schizophrenia Randomized to Olanzapine Long-Acting Injection or Oral Olanzapine

Early response predicts subsequent response to olanzapine long-acting injection in a randomized, double-blind clinical trial of treatment for schizophrenia

BackgroundIn patients with schizophrenia, early non-response to oral antipsychotic therapy robustly predicts subsequent non-response to continued treatment with the same medication. This study assessed whether early response predicted later response when using a long-acting injection (LAI) antipsychotic.MethodsData were taken from an 8-week, randomized, double-blind, placebo-controlled study of olanzapine LAI in acutely ill patients with schizophrenia (n = 233). Early response was defined as ≥30% improvement from baseline to Week 4 in Positive and Negative Syndrome Scale (PANSS0-6) Total score. Subsequent response was defined as ≥40% baseline-to-endpoint improvement in PANSS0-6 Total score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and predictive accuracy were calculated. Clinical and functional outcomes were compared between Early Responders and Early Non-responders.ResultsEarly response/non-response to olanzapine LAI predicted later response/non-response with high sensitivity (85%), specificity (72%), PPV (78%), NPV (80%), and overall accuracy (79%). Compared to Early Non-responders, Early Responders had significantly greater improvement in PANSS0-6 Total scores at all time points and greater baseline-to-endpoint improvement in PANSS subscale scores, Quality of Life Scale scores, and Short Form-36 Health Survey scores (all p ≤ .01). Among Early Non-responders, 20% demonstrated response by Week 8. Patients who lacked early improvement (at Week 4) in Negative Symptoms and Disorganized Thoughts were more likely to continue being non-responders at Week 8.ConclusionsAmong acutely ill patients with schizophrenia, early response predicted subsequent response to olanzapine LAI. Early Responders experienced significantly better clinical and functional outcomes than Early Non-responders. Findings are consistent with previous research on oral antipsychotics.Clinical Trials RegistryF1D-MC-HGJZ: Comparison of Intramuscular Olanzapine Depot With Placebo in the Treatment of Patients With Schizophrenia http://clinicaltrials.gov/ct2/show/NCT00088478?term=olanzapine+depot&rank=3Registry identifier - NCT00088478

P.3.c.017 Effectiveness and tolerability of olanzapine long-acting injection versus first-generation depot for schizophrenia: clinical outcomes

P.3.c.017 Effectiveness and tolerability of olanzapine long-acting injection versus first-generation depot for schizophrenia: clinical outcomes

Comparison of metabolic changes in patients with schizophrenia during randomized treatment with intramuscular olanzapine long‐acting injection versus oral olanzapine

Metabolic changes were examined in patients with schizophrenia during treatment with either oral olanzapine or olanzapine long-acting injection (LAI). Data were collected from patients who had been stabilized on oral olanzapine (10, 15, or 20 mg/day) for ≥4 weeks and then randomized to either continued olanzapine oral treatment (n = 322) or LAI (n = 599; 150 mg/2 weeks, 405 mg/4 weeks, or 300 mg/2 weeks) for up to 24 weeks. Mean and categorical changes in metabolic parameters were analyzed. Mean changes in weight, glucose, and most lipids were generally not significantly different between treatment groups. Weight changes over time followed similar patterns and were not significantly different at endpoint between the two treatment-formulation groups. Low-density lipoprotein cholesterol decreased significantly less among olanzapine LAI-treated patients. Percentages of patients with potentially clinically significant changes in blood glucose and lipid concentrations were similar for the two treatments. Percentages of patients experiencing adverse events related to weight, diabetes, or dyslipidemia were also not significantly different between treatments. Metabolic changes in patients with schizophrenia appeared generally similar during treatment with oral olanzapine or olanzapine LAI.

Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model

Objective:To compare, from the perspective of third-party payers in the United States health care system, the cost-effectiveness of olanzapine long-acting injection (LAI, depot) with alternative antipsychotic agents including risperidone-LAI, paliperidone-LAI, haloperidol-LAI, and oral olanzapine, in the treatment of patients with schizophrenia who have been non-adherent or partially adherent with oral antipsychotics.Research design and methods:A 1-year micro-simulation economic decision model was developed to simulate the dynamics of usual care of patients with schizophrenia who continue, discontinue, switch, or restart their medication. The model uses a range of clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation rates by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct health care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions.Outcome measures:Key model outputs include annual total direct cost (US$) per treatment and incremental cost-effectiveness values per additional QALY gained.Results:Model results found that the olanzapine-LAI treatment strategy was more effective (greater QALYs) and less costly than risperidone-LAI, paliperidone-LAI, and haloperidol-LAI. In addition, olanzapine-LAI was both more effective and more costly, with an estimated incremental cost/QALY of $26,824 compared to oral olanzapine. The base-case and multiple sensitivity analyses found olanzapine-LAI to remain within acceptable cost-effective ranges (<$50,000) in terms of incremental cost/QALY gained.Conclusions:This micro-simulation model finds the olanzapine-LAI treatment strategy to result in better effectiveness and to be a cost-effective alternative compared to oral olanzapine and the LAI formulations of risperidone, paliperidone, and haloperidol in the treatment of non-adherent and partially adherent patients with schizophrenia in the United States. A key limitation is the assumption how LAI therapies compare to oral counterparts due to sparse head-to-head data. Further research is needed to verify baseline assumptions.

P03-303 - Improvement in patient symptoms and functioning during long-term treatment with olanzapine long-acting injection (OLAI)

Introduction, objectives and aimsTo evaluate the outcome of patients with schizophrenia during maintenance treatment with OLAI.MethodsData from three studies with OLAI were pooled and patients classified according to a cluster analysis [Lipkovich, Psychiatry Res, 2009] into five categories according severity of psychiatric symptoms (sx) and functional impairment (imp):A(minimal sx/mild imp),B(minimal sx/moderate imp),C(moderate sx/mild to moderate imp),D(moderate sx/severe imp),E(moderate to severe sx/severe imp).Improvement was defined as a change from B or C to A, or from D or E to A, B or C. Changes between the categories in the 6 months were analyzed. Stepwise logistic regression modeling was done to determine factors associated with improvement.Results1182 patients were classified. Patients who remained in the studies at 6 months had lower baseline CGI-S (3.04 vs 3.28, p &lt; 0.001), lower PANSS (61.38 vs 64.05, p = 0.012) and higher QLS (1.76 vs 1.39, p = 0.001). (Table 1) As patients in category A couldn’t improve and in category D&amp;E couldn’t worsen, 261(39%) patients from categories B, C, D and E improved and only 55(10%) from categories A, B and C got worse during 6 months. Baseline factors associated with improvement were: baseline category (p &lt; 0.001), CGI-S score (p = 0.022), and PANSS positive (p = 0.003)ConclusionsMajority of patients with schizophrenia who stay on 6 months treatment with OLAI improve or maintain their symptoms and functioning level. The strongest factor associated with a higher chance of improvement was poor baseline category.

Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia

BackgroundIn a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes.MethodsOutpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140), "medium" (405 mg/4 weeks; N = 318), or "high" (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data).ResultsSafety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose.ConclusionsAnalyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient.Trial RegistrationClinicalTrials.gov: NCT00088491

Long-Term Safety and Tolerability of Open-Label Olanzapine Long-Acting Injection in the Treatment of Schizophrenia: 190-Week Interim Results

The primary objective of this ongoing study is to examine the long-term safety and tolerability of olanzapine long-acting injection (LAI). Current results are from a 190-week interim analysis. Patients were 18–75 years of age with schizophrenia (N = 909) or schizoaffective disorder (N = 22) previously enrolled in 1 of 3 randomized clinical trials of olanzapine LAI. In this open-label extension study, all patients received flexibly-dosed olanzapine LAI every 2–4 weeks. At time of analysis, rate of study discontinuation was 46.3%. The 18-month discontinuation rate was 34.2%. Adverse events in ≥5% of patients were increased weight, insomnia, anxiety somnolence, headache, and nasopharyngitis. There were 26 occurrences of post-injection delirium/sedation syndrome which all fully resolved within 72 hours. Mean weight change was +1.81 kg, with 32.1% of patients experiencing ≥7% weight gain. Mean Clinical Global Impressions-Severity scores remained stable throughout (2.9 at baseline to 2.8 at endpoint). Pharmacokinetic analyses indicated consistent olanzapine plasma concentrations over time, with no evidence of long-term accumulation. Safety profile was consistent with that of oral olanzapine, with the exception of findings specific to intramuscular injection. During the study period, there were 16 (1.7%) occurrences of treatment-emergent diabetes and 1 occurrence of treatment-emergent diabetic ketoacidosis. Percentages of patients with EPS scale-defined treatment-emergent akathisia, parkinsonism, and dyskinesia were 3.3%, 6.6%, and 3.0%, respectively.

Dose correspondence between olanzapine long-acting injection and oral olanzapine

Oral-to-depot dose correspondence was explored in a 24-week study of olanzapine long-acting injection (LAI). Patients with schizophrenia stabilized on oral olanzapine of 10, 15, or 20 mg/day (n=1065) were randomized to continue their oral treatment or switch directly to a fixed dose of olanzapine LAI [(mg/weeks) 45/4, 150/2, 405/4, or 300/2] without oral supplementation. Six-month relapse rates for each LAI-dose group stratified by earlier oral dose were analyzed using a Cox proportional hazard model assessing risk of relapse relative to each oral dose. Relapse rates for the therapeutic LAI doses (≥ 150 mg) varied depending on earlier oral dose, ranging from 1.5% (patients switched from 10 mg/day to 300 mg/2 weeks) to 18.8% (patients switched from 20 mg/day to 150 mg/2 weeks). Switching from 10 mg/day to 405 mg/4 weeks produced a comparable risk of relapse as remaining on that oral dose [Hazard ratio (HR)=1.03]. Switching from 15 or 20 mg/day to 300 mg/2 weeks produced comparable risk of relapse as remaining on those oral doses (HR=0.68 and 1.13, respectively). Pharmacokinetic modeling was conducted to evaluate the resulting dosing recommendations. Findings suggest that patients can be switched directly from oral to olanzapine LAI without the need for oral supplementation and with a low risk of relapse when initiated on an appropriate LAI dose.

Patient and Health Care Provider Perspectives on Long Acting Injectable Antipsychotics in Schizophrenia and the Introduction of Olanzapine Long-Acting Injection

Olanzapine long acting injection has joined risperidone and paliperidone as the second generation long acting antipsychotic injection options for treatment of patients with schizophrenia. Long acting injections are important alternatives to oral medications for patients who have difficulty adhering to daily or multiple daily medication administrations, yet may be underutilized or not well understood. Patient perceptions, adherence, and preferences are important issues for health care providers to address when discussing treatment options with their patients. Reviewed here are overall patient and health care provider attitudes and perceptions regarding long acting injections and the details of olanzapine long acting injectable, the newest agent, and how it will fit in the marketplace. In addition, efficacy, safety, dosing and use data regarding this newest long acting agent are reviewed and compared to other available long acting agents.

Olanzapine Long-Acting Injection

Olanzapine pamoate (olanzapine long-acting injection [OLAI]; Zypadhera®; Zyprexa® Relprevv™) is the intramuscular depot formulation of the atypical antipsychotic olanzapine. In two pivotal, double-blind clinical trials of 8 or 24 weeks' duration, the efficacy of recommended dosages of OLAI injected every 2 or 4 weeks (without oral supplementation) was greater than that of placebo in improving symptoms in acutely ill patients with schizophrenia, and generally similar to that of continuing oral olanzapine in preventing psychotic exacerbations in patients with schizophrenia whose symptoms had previously been stabilized on oral olanzapine. The effectiveness of OLAI in the maintenance treatment of schizophrenia was also demonstrated in an (ongoing) open-label extension study in which the all-cause discontinuation rate was 34.3% after 18 months. OLAI is generally well tolerated. It has an adverse event profile similar to that of oral olanzapine, with the exception of adverse events related to the intramuscular route of administration; these include a manageable post-injection syndrome, which occurred in <0.1% of injections in clinical trials. The possibility of a post-injection syndrome event requires a risk management plan (RMP) to be adopted that includes observation by appropriately qualified personnel in a healthcare facility for at least 3 hours post-injection. With its potential to improve adherence to medication, and thereby treatment outcomes, OLAI is a useful addition to the pharmacological options available for the maintenance therapy of schizophrenia. Given its benefit/risk profile, OLAI appears most suited for patients who, despite responding well to oral olanzapine, have difficulties remaining adherent to this form of medication, provided they can comply with the conditions of the RMP.

PMH2 EARLY RESPONSE PREDICTS SUBSEQUENT RESPONSE TO OLANZAPINE LONG-ACTING INJECTIONS IN THE TREATMENT OF SCHIZOPHRENIA

Objective: Early non-response to oral antipsychotics was previously shown to be a robust predictor of subsequent non-response to continued treatment with the same oral antipsychotic medication in the treatment of schizophrenia. This study assessed whether early response or early non-response to treatment can serve as a clinical marker in the treatment of schizophrenia with an atypical antipsychotic in long-acting injection formulation (depot). Methods: This post-hoc analysis used data (n=233) from an 8-week randomized, double-blind, placebocontrolled study of olanzapine long-acting injection (olanzapine LAI) in the treatment of inpatients with schizophrenia. Early response to olanzapine LAI was defined as a ≥30% improvement on the PANSS total score (items scored 0-6) from baseline to 4 weeks of treatment. Subsequent response was defined as a ≥40% improvement on the PANSS total score from baseline to endpoint. Predictive accuracy was assessed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall predictive accuracy. Early responders and early nonresponders to olanzapine LAI were also compared on change in clinical and functional outcome measures. Results: Early response/non-response to olanzapine LAI, assessed following 4 weeks of treatment, predicted subsequent response/nonresponse with a high level of overall accuracy (79%), sensitivity (85%), specificity (72%), PPV (78%), and NPV (80%). Compared to early nonresponders, early responders had significantly longer time to all-cause treatment discontinuation, greater symptom improvement at all time points (per PANSS total and subscale scores), and greater improvement in quality of life and level of social functioning (all at p≤.01). Conclusions: In this study of inpatients with schizophrenia, early response to olanzapine LAI was found to be a robust predictor of subsequent response to the medication. Early responders experienced significantly better clinical and functional outcomes compared to early nonresponders and had longer treatment duration. Current findings are consistent with previous research on oral antipsychotics and will require replication in future studies.

P.3.c.011 Olanzapine long-acting injection vs oral olanzapine in schizophrenia outpatients: a 2-year, randomized, open-label study

P.3.c.011 Olanzapine long-acting injection vs oral olanzapine in schizophrenia outpatients: a 2-year, randomized, open-label study