One year mirror-image study using paliperidone palmitate for relapse prevention of schizophrenia in four university hospitals in Canada
Introduction
Although schizophrenia only affects approximately 1% of the Canadian population, it still remains one of the costliest illnesses. Estimates from 2004 demonstrated that the total costs attributed to schizophrenia totaled $6.85 billion CAN including productivity losses (Goeree et al., 2005). When the later are removed, this represents 5% of Canadian healthcare expenditures (Goeree et al., 2005). This mental illness can be treated with varying degrees of success with a combination of medication, psychological and social interventions.
Nonetheless, non-adherence remains a major issue that complicates the treatment of schizophrenia. Among 10 studies published since 1980, it was reported that the mean rate of non-adherence to antipsychotic medication was 41% whereas 5 studies meeting stricter inclusion criteria demonstrated a mean non-adherence rate of 49.5% (Lacro et al., 2002). Non-compliance to psychiatric treatment has been associated with increased hospital utilization, increased relapses, decreased quality of life, disease chronicity, deterioration of social functioning and increased health costs (Ascher-Svanum et al., 2006).
Long-acting intramuscular delivery was hoped to resolve the issue of non-compliance to antipsychotic treatments. Attempts were made by several authors to determine whether long-acting injectable antipsychotics (LAI) are more clinically effective. A meta-analysis of 21 randomized controlled trials demonstrated no significant difference in the effectiveness of LAIs over oral antipsychotics (Kishimoto et al., 2012). Nonetheless, rigorous inclusion criteria and follow-ups may have biased the representation of the psychiatric population initiated on LAI antipsychotics. For instance, patients with dual diagnosis and/or patients under community treatment order (CTO, a mandatory treatment ordered by a judge) are often excluded. Furthermore, a meta-analysis of 25 mirror-image studies comparing oral antipsychotic treatment with a subsequent period of LAI treatment showed LAI superiority over oral antipsychotics in preventing hospitalizations with a risk ratio of 0.43 in 14 out of 16 studies (Kishimoto et al., 2013). The literature on the superiority of LAIs over oral antipsychotics therefore remains controversial and dependent on study design and inclusion criteria.
Paliperidone palmitate (PP), a long-acting injectable antipsychotic, was added in 2011 to Quebec's formulary. Since then, its use has grown in popularity given its advantages over its predecessors including quick onset of action and once-monthly administration. As of yet, no Canadian study has been designed to assess whether PP is more effective and cost-effective than oral antipsychotics. However, other groups have asked this question, and the answer varies depending on country (Bera et al., 2013, Bressington et al., 2015, Taylor and Olofinjana, 2014).
We aimed to evaluate whether adherence to PP is improved in comparison to oral antipsychotics on the Canadian market and whether its therapeutic advantages can result in decreased hospitalization. Despite its significant cost of acquisition, it remains to be determined whether it is a cost-effective treatment. Quebec guidelines recommend the use of LAI when poor treatment adherence is noted or when it's the patient's preference (Stip et al., 2011). We hypothesized that patients with problematic compliance and high hospitalization rate would benefit from introduction of PP, resulting in lower hospitalizations and healthcare cost savings.
Section snippets
Study design
A retrospective mirror-image study was designed (Fig. 1) to determine the efficiency of PP compared to standard oral antipsychotic treatment. We defined the date of the first injection of PP as the index event, thereby using this date as the cut-off point for determining the pre-initiation (AB) and post-initiation periods (CD). The study, being multi-centered, used data collected from four Canadian centers: the Institut universitaire en santé mentale de Montréal (IUSMM, Montreal, Quebec),
Patients
We gathered drug exposure and hospitalization periods for 328 patient-years in 114 patients. Approximately 550 patients were excluded from the study because of previous exposure to a LAI (30%) or to clozapine (15%), were lost to follow-up (12%), refused to participate (7%), were never prescribed oral antipsychotics (7%), or other reasons (11%). Seventy-seven percent were male, mean age 37 years old (18–64 years), mean duration of illness 10 years (0–42 years), of which 70% had schizophrenia, 30%
Discussion
This study has revealed that initiating PP as a first LAI in a cohort of Canadian schizophrenic and schizoaffective patients improved adherence to pharmacological treatment and decreased the frequency of hospital visits with an overall net effect in government health expenditures. These results suggest that in schizophrenic patients demonstrating low adherence to oral antipsychotics, PP remains an efficient and cost-neutral therapeutic strategy in comparison to the sole use of oral
Conclusion
We believe that a higher efficacy can be assumed from the increased drug exposure with LAI in our cohort. This led to a meaningful reduction in the patient's use of hospital services. Our study sheds light on another problem to investigate, which is the long delay before LAI are initiated. Our patients suffered from schizophrenia or schizoaffective disorder for a mean 10 years, had a mean adherence rate of 43% and still, PP was their first LAI trial. We believe that a better monitoring of
Role of the funding source
An unrestricted educational grant from Janssen Canada (JCAEDG00468) was used to support this study.
Contributors
Philippe Vincent designed and coordinated the research project, recruited patients, interpreted the data, did statistical analysis and wrote the manuscript. Alex Halme interpreted the data and helped with statistical analysis. Josée Duchesneau, Marie-France Demers and Violaine Masson helped recruit patients in their hospital. Venessa Doyon-Kemp recruited patients, wrote the manuscript draft, and helped with grammar and language. All authors read and approved of the final manuscript.
Conflicts of interest
P. D. Vincent reports personal fees from Apotex, personal fees from Eli Lilly, grants and personal fees from Janssen Canada, personal fees from Lundbeck/Otsuka, personal fees from Pfizer, personal fees from Uniprix, all outside the submitted work
M.-F. Demers reports grants from Lundbeck, personal fees from Otsuka, personal fees from Mylan, grants from Janssen, all outside the submitted work
V. Masson reports personal fees from Otsuka-Lundbeck, outside from the submitted work
A. Halme, J.
Acknowledgments
We wish to thank Ingrid Agbado, Sandra Bilodeau, Katy Lavoie and Akram Djouini for help recruiting patients and collecting data, all nurses and psychiatrists who referred patients in our hospitals, Chantal Vallières, research coordinator in IUSMQ, all pharmacists at IUSMQ, especially Catherine Lesueur, Nathalie Couillard, Esthel Malenfant and Guillaume Chalifour.
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Cited by (24)
A 10-year mirror-image study of effectiveness and cost of long-acting paliperidone palmitate injectable in patients with schizophrenia or schizoaffective disorder
2022, Psychiatry ResearchCitation Excerpt :In the literature, there is an interesting amount of mirror-studies evaluating these variables, with positive results. However, they have a shorter observation period, mostly 1 year (Bressington et al., 2015; Chan et al., 2021; di Lorenzo et al., 2019; Hodgson, 2019; Lee et al., 2020; Mahabaleshwarkar et al., 2021; Mahlich et al., 2020; Oh et al., 2019; Vincent et al., 2017), 2 years (Taylor et al., 2016) and 3 years (Nikolić et al., 2017; Pappa et al., 2019) of follow-up. To our knowledge, this is the first 1MPP mirror-study with a 10-year observation time.
Effect of 3-monthly paliperidone palmitate on hospitalisation in a naturalistic schizophrenia cohort – A five-year mirror image study
2022, Journal of Psychiatric ResearchCitation Excerpt :Perhaps because of this poorer tolerability, there is a higher risk of hospitalisation in patients prescribed FGA LAIs than those on SGA LAIs(Wu et al., 2016). Paliperidone palmitate once-monthly LAI (PP1M) is a SGA LAI that has been shown to reduce relapse and hospitalisation risk in patients with schizophrenia(Vincent et al., 2017). Mirror-image studies suggest significant reduction in hospital stay, relapse and bed days in patients prescribed PP1M(Nikolic et al., 2017; Taylor and Olofinjana, 2014; Taylor, D. M. et al., 2016).
Effectiveness of Paliperidone Palmitate on Treatment Adherence and Relapse in the Adult Schizophrenia Population: A One-Year Mirror-Image Study in a Colombian Mental Health Care Facility
2022, Revista Colombiana de PsiquiatriaCitation Excerpt :Previous studies have also shown that the removal of the index hospitalization not only affected hospitalization rate but also accentuated the beneficial effect of PP1M on total LoS. It was therefore suggested that PP1M would be more cost-effective when started in an outpatient setting.12 To further elucidate this hypothesis, the effect of PP1M on hospitalization rate and LoS, stratification of findings according to initiation setting (inpatient or outpatient) would need to be conducted.
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
2021, The Lancet PsychiatryCitation Excerpt :The initial search provided 14 687 records, of which 11 493 records were excluded after title screening because they were not relevant or duplicates. Of the remaining 3194 records, 3057 were excluded after screening and assessment of abstracts and full texts, yielding 137 studies (32 RCTs [23·4%; 8577 patients],21–51 65 cohort studies [47·4%; 377 447 patients],52–115 and 40 pre–post studies [29·2%; 11 295 patients]116–155; figure 1). For one cohort study we extracted all data from the published abstract.74
Second-generation LAI are associated to favorable outcome in a cohort of incident patients diagnosed with schizophrenia
2018, Schizophrenia ResearchCitation Excerpt :The results from the current study showing a reduction in number of hospitalizations of approximately 0.57 is in line with a meta-analysis from Kishimoto et al. (2013) based on 25 mirror-image studies, which showed a reduction in number of hospitalizations of 0.38. A recent small study by Vincent et al. (2017)) investigating paliperidone palmitate showed a reduction in admissions to approximately one third after LAI initiation, but with no difference in days hospitalized. Similarly Mesones-Peral et al. (2017) also recently found reductions in admissions and bed days associated with paliperidone palmitate.
Effectiveness of Paliperidone Palmitate in Reducing Acute Psychiatric Service Use for Patients Suffering from Psychosis—A Retrospective Mirror-Image Study
2023, International Journal of Environmental Research and Public Health
- 1
Present address: Pharmacie Paul St-Onge, André St-Onge et Clément Pelletier, Brossard, Canada.
- 2
Present address: Mcgill University Health Center, Montreal, Canada.