Treatment Patterns and Outcomes from OASIS: A Prospective Observational Study of Long-Acting Injectables in Schizophrenia

Antipsychotic medications are a central component of effective treatment for schizophrenia, but nonadherence is a significant problem for the majority of patients. Long-acting injectable (LAI) antipsychotic medications are a recommended treatment option for nonadherent patients, but evidence regarding their potential advantages has been mixed. Observational data on newer, second-generation LAI antipsychotic medications have been limited given their more recent regulatory approval and availability. To examine antipsychotic medication nonadherence, discontinuation, and rehospitalization outcomes in Medicaid patients receiving oral versus LAI antipsychotic medications in the 6 months after a schizophrenia-related hospitalization. The 2010-2013 Truven Health Analytics MarketScan Medicaid research claims database was used to identify adult patients with a recent history of nonadherence (prior 6 months) who received an oral or LAI antipsychotic medication within 30 days after an index schizophrenia-related hospitalization. Primary outcome measures were nonadherence (proportion of days covered less than 0.80), discontinuation (continuous medication gap ≥ 60 days), and schizophrenia-related rehospitalization, all in the 6 months after discharge. Descriptive analyses compared users of oral versus LAI antipsychotic medication on sociodemographic, clinical, and treatment characteristics. Logistic regressions were used to examine associations between use of oral versus LAI antipsychotics and each study outcome while controlling for observed differences in sample characteristics. All outcomes were compared at 3 levels of analysis: overall LAI class, LAI antipsychotic generation (first-generation [FGA] or second-generation [SGA] antipsychotics), and individual LAI agent (fluphenazine decanoate, haloperidol decanoate, risperidone LAI, and paliperidone palmitate). Of the final sample, 91% (n = 3,428) received oral antipsychotics, and 9.0% (n = 340) received LAI antipsychotics after discharge. Slightly over half (n =183, 53.8%) of LAI users used an SGA LAI. A smaller percentage of patients receiving LAIs were nonadherent (51.8% vs. 67.7%, P less than 0.001); had a 60-day continuous gap in medication (23.8% vs. 39.4%, P less than 0.001); and were rehospitalized for schizophrenia (19.1% vs. 25.3%, P = 0.01) compared with patients receiving oral medications. The size of these differences was magnified when comparing SGA LAI users with users of oral antipsychotics for nonadherence. After controlling for all differences in measured covariates, LAI initiators had lower odds of being nonadherent (adjusted odds ratio [AOR] = 0.35, 95% CI = 0.27-0.46, P less than 0.001) and of having continuous 60-day gaps (AOR = 0.45, 95% CI = 0.34-0.60, P less than 0.001) when compared with patients receiving oral medications. Both FGA and SGA LAI users had lower odds of nonadherence compared with patients receiving oral antipsychotics. Similarly, FGA LAI users (AOR = 0.58, 95% CI = 0.40-0.85, P = 0.005) and SGA LAI initiators (AOR = 0.34, 95% CI =0.23-0.51, P less than 0.001) had lower odds of a 60-day continuous gap compared with patients receiving oral antipsychotics. Compared with those receiving oral antipsychotics, LAI initiators also had lower odds of rehospitalization (AOR = 0.73, 95% CI = 0.54-0.99, P = 0.041); however, when examined separately, only patients receiving SGA LAIs (AOR = 0.59, 95% CI = 0.38-0.90, P = 0.015) and not FGA LAIs (AOR = 0.90, 95% CI = 0.60-1.34, P = 0.599) had a statistically significant reduction in odds of rehospitalization. Among individual LAIs, odds of rehospitalization only among initiators of paliperidone palmitate were statistically different from those among users of oral antipsychotics (AOR = 0.53, 95% CI = 0.30-0.94, P = 0.031). While odds of rehospitalization were 33% lower among patients receiving risperidone LAI compared with those receiving oral antipsychotics, the estimate did not reach statistical significance (AOR = 0.67, 95% CI = 0.37-1.22, P = 0.194). This claims-based analysis of posthospitalization adherence and rehospitalization outcomes in Medicaid patients with schizophrenia adds to the growing real-world evidence base of the benefits of LAI antipsychotic medications in routine clinical practice, particularly with regard to second-generation LAIs. As new SGA formulations become available for long-acting use, real-world studies with larger sample sizes will be needed to further delineate their potential advantages in terms of clinical outcomes and costs.

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.

Clinicians using long-acting injectable (LAI) antipsychotics may assume that there is uniformity in the injection technique for all LAIs. However, because LAIs have significant differences in their formulation, each requires a specific administration procedure. Here, we focus on how the formulation properties of the atypical LAI aripiprazole lauroxil impact its administration.The history of LAI formulations is presented as a background to recent advances in formulation technology. A shared challenge for new LAIs is to adapt the formulation of insoluble drugs to aqueous-based suspensions.The early LAIs kept the drug product dissolved as oil-based solutions, which were stable and did not require mixing prior to injection. However, oil-based solutions tend to be viscous and cause injection-site reactions (ISRs).New LAI formulations tend to be aqueous-based suspensions and need to be resuspended or reconstituted before injection. Beyond this common element, formulation properties lead to differences in administration for each of the available LAIs.We reviewed the formulations of LAIs indicated for the treatment of schizophrenia and how they impact instructions for use, with a focus on aripiprazole lauroxil.Aripiprazole monohydrate and olanzapine pamoate are lyophilized powders that require reconstitution before administration and should be injected slowly. Risperidone is formulated as microspheres in powder form that require reconstitution before injection, although the injection speed is not specified. Paliperidone palmitate is a ready-to-use aqueous suspension of crystalline particles and should be injected slowly. Aripiprazole lauroxil is an aqueous-based, ready-to-use suspension of crystalline particles. Unlike other LAIs, the formulation of aripiprazole lauroxil contains particles that are loosely associated to facilitate resuspension. Because loosely associated suspensions are shear-thinning, meaning the viscosity of the formulation decreases with higher injection force, the injection must be given rapidly. Vigorous shaking and rapid injection are key aspects of administration and have been accepted by patients and investigators in clinical trials. In a pivotal phase 3 study of aripiprazole lauroxil, the incidence of ISRs was low (3.9% and 5.8% for aripiprazole lauroxil 441mg and 882mg , respectively) and mostly associated with the first injection.Advances in formulation technology have increased LAI options for patients with schizophrenia. The aripiprazole lauroxil formulation differs from other LAIs in that the particles are loosely associated to support use as a ready-to-use pre-filled syringe. Because the suspension is shear-thinning, aripiprazole lauroxil requires rapid injection, which is not required when using other LAIs. An understanding of the differences in formulation design and how they impact the specific techniques associated with an LAI is essential for successful administration.Funding Acknowledgements: This study was funded by Alkermes, Inc.

Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients. MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. 33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations. While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.

How Would You Like to Take Your Medicine 2 Times a Year? Paliperidone Palmitate Every 6 Months for the Maintenance Treatment of Schizophrenia

This post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risperidone long-acting injectable (RLAI), in subjects with schizophrenia experiencing clinically significant symptoms despite recent treatment with oral risperidone only or other oral antipsychotics. Adult subjects were eligible for the 13-week, double-blind, double-dummy trial (NCT00589914) if they had an established diagnosis of schizophrenia for at least one year and a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 inclusive at screening. Subjects received either paliperidone palmitate (234 mg, day 1; 156 mg, day 8; then once-monthly flexible dosing) or RLAI (25-50 mg biweekly, with oral risperidone supplementation on days 1-28), plus matched placebo injections/tablets. This post hoc analysis reports data on 747 subjects who, within 2 weeks of starting double-blind study medication, had reportedly received oral risperidone only (paliperidone palmitate group, n = 126; RLAI group, n = 107), other oral antipsychotics (paliperidone palmitate group, n = 199; RLAI group, n = 203), or no antipsychotic (paliperidone palmitate group, n = 56; RLAI group, n = 56). Mean PANSS total scores improved significantly at end point across all subgroups (mean change from baseline ranged from -17.5 to -19.5, all P < 0.0001). Clinical Global Impression-Severity and Personal and Social Performance scale measures also significantly improved from baseline (all P < 0.0001). Treatment with paliperidone palmitate or RLAI resulted in a significant reduction in the symptoms of schizophrenia irrespective of previous recent treatment with oral risperidone only or other oral antipsychotics. For subjects who had previously received oral risperidone only, the difference in formulation was the main change in the intervention because the molecule delivered remained the same or similar. These data support the contribution of a long-acting formulation to improving the treatment response and suggest that nonadherence may be a significant contributor to inadequate efficacy of oral formulations in subjects with schizophrenia.

In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan-Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time.

Nonadherence for first-episode schizophrenia is a major unsolved challenge. The long-acting injectable route is an appealing strategy, but there are concerns about acceptability. We report on acceptance and initial adherence outcomes with risperidone long-acting injection (RLAI) in first-episode schizophrenia patients. We conducted a prospective randomized controlled trial in which we enrolled patients defined by appropriate Structured Clinical Interview for DSM-IV diagnosis and < or = 16 weeks of lifetime antipsychotic exposure. Participants were randomly assigned (2:1 ratio) to a recommendation of changing to RLAI versus continuing on oral therapy (ORAL). Nonadherence behavior was defined as a medication gap > or = 14 days. Adherence attitudes were determined by the Rating of Medication Influences (ROMI) scale. A priori analysis defined treatment groups as intent-to-treat (ITT) and as-actually-treated (AAT) for the first 12 weeks after initial randomization. Participants were enrolled from December 2004 to March 2007. Of 46 eligible patients, 37 were randomly assigned, 11 to ORAL and 26 to RLAI. Nineteen of 26 patients (73%) accepted the RLAI recommendation. There were no differences in adherence behavior at 12 weeks based on initial randomization (Kaplan-Meier survival for ITT: 76% [95% CI, 35%-90%] adherent for RLAI vs 72% [95% CI, 55%-89%] for ORAL; log-rank P = .78), but patients accepting RLAI were significantly more likely to be adherent than patients staying on ORAL (AAT: 89% [95% CI, 64%-97%] adherent for RLAI vs 59% [95% CI, 32%-78%] for ORAL; log-rank P = .035). There were no ROMI attitude differences between either treatment group comparison at 12 weeks. Most first-episode patients taking oral antipsychotics will accept a recommendation of RLAI therapy. On the basis of initial randomization status, an RLAI recommendation did not affect adherence behavior at 12 weeks. However, acceptance of RLAI was associated with significantly better adherence. Regardless of whether RLAI is recommended or accepted, there is no adverse impact on subsequent medication attitudes at 12 weeks. These results support the feasibility and acceptability of introducing RLAI as a treatment option for first-episode schizophrenia patients. clinicaltrials.gov Identifier: NCT00220714.

In the last few years, oral second-generation antipsychotics have demonstrated mood-stabilizing properties and are now widely used in the treatment of bipolar disorder. Unfortunately, treatment of this chronic and complex illness is hampered with poor adherence on the part of patients. Long-acting injectable formulations of second-generation antipsychotics could combine the effect of oral second-generation antipsychotics in patients with bipolar disorder and the benefits of depot formulation with the assurance of steady medication delivery and thereby improve adherence. In this context, the efficacy and tolerance of risperidone long-acting injection (RLAI) for maintenance treatment in patients with bipolar disorder is assessed. The relevant studies found RLAI to be effective in preventive treatment of manic but not depressive recurrences in bipolar patients, with good tolerance. RLAI appeared to be particularly suitable for patients with known poor adherence to treatment or severe bipolar disorder (such as patients who relapse frequently). Lastly, if RLAI, unlike the first-generation antipsychotics, does not induce depressive symptoms, the different studies do not enable us to consider its use in monotherapy in the preventive treatment of patients with depressive polarity. Long-acting second-generation antipsychotics in bipolar patients are therefore associated with long-term benefits, but their use in clinical practice needs to be improved.

P-1323 - Improvement of prognosis through long acting risperidone versus combined adherence focused psychotherapy and oral antipsychotics in chronic schizophrenia

Objective:To assess the impact of long-acting injectables (LAIs) versus oral antipsychotics (OAs) on hospitalizations among patients with schizophrenia by conducting a systematic literature review of studies with different study designs and performing a meta-analysis.Methods:Using the PubMed database and major psychiatric conference proceedings, a systematic literature review for January 2000 to July 2013 was performed to identify English-language studies evaluating schizophrenia patients treated with atypical antipsychotics. Studies reporting hospitalization rates as a percentage of patients hospitalized or as the number of hospitalizations per person per year were selected. The primary meta-analysis assessed the percentage decrease in hospitalization rates before and after treatment initiation for matched time periods. The secondary meta-analysis assessed the absolute rate of hospitalization during follow-up. Pooled treatment-effect estimates were calculated using random-effects models. To account for differences in patient and study-level characteristics between studies, meta-regression analyses were used. Subset analyses further explored the heterogeneity across study designs.Results:Fifty-eight studies evaluating 25 arms (LAIs: 13 arms, 4516 patients; OAs: 12 arms, 23,516 patients) in the primary meta-analysis and 78 arms (LAIs: 12 arms, 4481 patients; OAs: 66 arms, 96,230 patients) in the secondary meta-analysis were identified. Reduction in hospitalization rates for LAIs was 20.7 percentage points higher than that of OAs (random-effects estimates: LAIs = 56.2% vs. OAs = 35.5%, P = 0.023). Controlling for patient and study characteristics, the adjusted percentage reduction in hospitalization rates for LAIs was 26.4 percentage points higher than for OAs (95% CI: 3.3–49.5, P = 0.027). As for the secondary meta-analysis, no significant difference between LAIs and OAs was observed (random-effects estimate: −8.6, 95% CI: −18.1–1.0, P = 0.077). Subset analyses across type of study yielded consistent results. Limitations of this analysis include the long observation period, which may not reflect current treatment patterns, the use of all-cause hospitalization, which may not be solely related to schizophrenia, and the fact that most studies in the LAI cohort evaluated risperidone.Conclusion:The primary results of this meta-analysis, including studies with both interventional and non-interventional designs and using meta-regressions, suggest that LAIs are associated with higher reductions in hospitalization rates for schizophrenia patients compared to OAs.

BackgroundSchizophrenia often requires long-term treatment with antipsychotics. Paliperidone palmitate long-acting injection (PPLAI) is one of the advantageous options to maintain adherence, prevent relapse and hospitalization (Kishimoto et al., 2021; Tiihonen et al., 2017). In Japan, paliperidone palmitate 1-monthly (PP1M) and paliperidone palmitate 3-monthly (PP3M) have been approved, and the approved patient population for PP3M in Japan is limited to patients with schizophrenia who have been stabilized with PP1M monotherapy. Antipsychotic polypharmacy consisting of LAI and oral antipsychotics (OAPs) are widely used in the clinical practice in many countries (Doshi et al., 2015; Aggarwal et al., 2012; Dimitropoulos et al., 2017; Cordiner et al., 2016; Joo et al., 2019), including Japan (Onitsuka et al., 2023). Hence, LAI monotherapy may be a more appropriate option in the long term. However, to date, factors associated with continuation for LAI monotherapy have not been examined. Therefore, we conducted a post-hoc analysis of a post-marketing surveillance (PMS) to explore factors associated with subsequent treatment continuation in patients who introduced PP1M monotherapy.Aims & ObjectivesThe purpose of the post-hoc analysis is to identify factors associated with subsequent treatment continuation in schizophrenia patients in whom PP1M was introduced as a monotherapy.MethodThis study is a post-hoc analysis of the PMS in PP1M in Japan. The case enrollment period was from January 2014 to July 2015, and patients with schizophrenia who received PP1M according to the dosage and administration in the package insert were enrolled. The primary analysis population will be 698 of the 1306 patients enrolled in the PMS who were being treated with PP1M monotherapy treatment at the start of PP1M. Main endpoint will include time to drop out of monotherapy (all causes of dropping PP1M monotherapy). Factors associated with continuation of PP1M monotherapy will be assessed by using cox regression model. In this presentation, we will report on factors associated with subsequent treatment continuation in schizophrenia patients where PP1M was introduced as monotherapy.ReferencesKishimoto, T., Hagi, K., Kurokawa, S., Kane, J. M., &Correll, C. U. (2021). Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies. The lancet. Psychiatry, 8(5), 387–404. https://doi.org/10.1016/S2215-0366(21)00039-0Tiihonen, J., Mittendorfer-Rutz, E., Majak, M., Mehtä lä, J., Hoti, F., Jedenius, E., Enkusson, D., Leval, A., Sermon, J., Tanskanen, A., &Taipale, H. (2017). Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29823 Patients With Schizophrenia. JAMA psychiatry, 74(7), 686–693. https://doi.org/10.1001/jamapsychiatry.2017.1322Doshi, J. A., Pettit, A. R., Stoddard, J. J., Zummo, J., &Marcus, S. C. (2015). Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge. Journal of clinical psychopharmacology, 35(4), 442–446. https://doi.org/10.1097/JCP.0000000000000353Aggarwal, N. K., Sernyak, M. J., &Rosenheck, R. A. (2012). Prevalence of concomitant oral antipsychotic drug use among patients treated with long-acting, intramuscular, antipsychotic medications. Journal of clinical psychopharmacology, 32(3), 323–328. https://doi.org/10.1097/JCP.0b013e31825244f6Dimitropoulos, E., Drogemuller, L., &Wong, K. (2017). Evaluation of Concurrent Oral and Long-Acting Injectable Antipsychotic Prescribing at the Minneapolis Veterans Affairs Health Care System. Journal of clinical psychopharmacology, 37(5), 605–608. https://doi.org/10.1097/JCP.0000000000000755Cordiner, M., Shajahan, P., McAvoy, S., Bashir, M., &Taylor, M. (2016). Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate. Therapeutic advances in psychopharmacology, 6(2), 66–76. https://doi.org/10.1177/2045125315623584Joo, S. W., Shon, S. H., Choi, G., Koh, M., Cho, S. W., &Lee, J. (2019). Continuation of schizophrenia treatment with three long-acting injectable antipsychotics in South Korea: A nationwide population- based study. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(9), 1051–1060. https://doi.org/10.1016/j.euroneuro.2019.07.138Onitsuka, T., Okada, T., Hasegawa, N., Tsuboi, T., Iga, J. I., Yasui-Furukori, N., Yamada, N., Hori, H., Muraoka, H., Ohi, K., Ogasawara, K., Shinichiro, O., Takeshima, M., Ichihashi, K., Fukumoto, K., Iida, H., Yamada, H., Furihata, R., Makinodan, M., Takaesu, Y., … Hashimoto, R. (2023). Combination Psychotropic Use for Schizophrenia With Long-Acting Injectable Antipsychotics and Oral Antipsychotics: A Nationwide Real-World Study in Japan. Journal of clinical psychopharmacology, 10.1097/JCP.0000000000001704. Advance online publication. https://doi.org/10.1097/JCP.0000000000001704

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.

In a previous meta-analysis of mirror-image studies, long-acting injection (LAI) significantly reduced the length of hospital stay compared to the reduction by an oral antipsychotic.1 On the other hand, to our knowledge, reports that have evaluated the comparison between hospitalization risk before and after risperidone LAI (RLAI) discontinuation are scarce. Therefore, we examined the comparison of hospitalization risk for the 6 months before and after changing from RLAI to another long-acting injection or oral antipsychotic in a clinical setting by using a mirror-image analysis. This was a mirror-image design involving patients with schizophrenia basis who were given RLAI between July 2009 and November 2015 at the psychiatry department of Fukui Kinen Hospital. This study was approved by the ethics committee of Fukui Kinen Hospital. The primary outcome measures were the rates of hospitalization within 6 months before and after RLAI discontinuation. Testing of independence was done using Fisher's exact test. The significance level was P < 0.05. A total of 88 patients discontinued RLAI after having continued it for 6 months or more. However, 31 patients who were hospitalized throughout the investigation period were excluded. Therefore, we analyzed 57 patients (male/female, 28/29, 49.1%/50.9%). The mean ± SD age was 41.6 ± 14.8 years and duration of illness was 16.0 ± 11.1 years. The mean Global Assessment of Functioning (GAF) score was 45.3 ± 11.0. The mean number of hospitalizations before the study enrollment was 0.4 ± 0.7. The hospitalization rate during RLAI continuation was 29.8% (17/57). Within 6 months of discontinuing RLAI, three patients discontinued their hospital visits, and two patients died. After discontinuing RLAI, 25 patients switched to another LAI, and 27 patients switched to oral antipsychotics. Of these, three patients restarted RLAI within 6 months of switching to oral antipsychotics. The rates of hospitalization within 6 months of switching to another LAI or oral antipsychotic following RLAI discontinuation were 28% (7/25) and 25% (6/24), and no significant difference was seen in hospitalization risk for the 6 months after RLAI discontinuation (risk ratio = 0.89; 95% confidence interval, 0.35–2.28; P = 0.82). The limitations of a mirror-image study are the expectancy effect, natural course of disease, and the possibility of influence of time as a bias. However, the mirror-image study performed is considered to reflect the true state of treatment given in clinical practice better than a randomized controlled trial, which is a gold standard in clinical studies for comparison of the hospitalization risk for the period of 6 months after RLAI discontinuation in the same patients. In the present study, no significant difference was seen in hospitalization risk for the 6 months after RLAI discontinuation; this finding was similar to the findings obtained in previous studies in which a mirror-image analysis was performed.2 Therefore, no difference was found between the hospitalization risk before RLAI discontinuation and that after RLAI discontinuation following switching to another LAI or oral antipsychotic. Dr Suzuki has received honoraria from Janssen, Otsuka, Dainippon Sumitomo, Shionogi, and Yoshitomiyakuhin. Dr Hibino has received honoraria from Janssen, Lilly, Otsuka, and Glaxo-SmithKline. Dr Inoue has received honoraria from Eisai and Novartis. Dr Takaya has received payment from Otsuka and Yoshitomiyakuhin.

BackgroundSchizophrenia is a serious mental health condition that causes disordered ideas, beliefs and experiences. The primary treatment is medicines. Non-compliance is one of the major problems of drop out. An...