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      Comparison and predictors of treatment adherence and remission among patients with schizophrenia treated with paliperidone palmitate or atypical oral antipsychotics in community behavioral health organizations

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          Abstract

          Background

          Nonadherence to antipsychotic treatment increases the likelihood of relapse and progressive symptomatology in patients with schizophrenia. Atypical long-acting injectables, including paliperidone palmitate (PP), may increase adherence and improve symptoms. This study compared and assessed predictors of treatment patterns and symptom remission among schizophrenia patients treated with PP versus atypical oral antipsychotic therapy (OAT) in community behavioral health organizations (CBHOs).

          Methods

          This retrospective cohort analysis evaluated 763 patients with schizophrenia and new (PP-N; N = 174) or continuing (PP-C; N = 308) users of PP, or new users of OAT ( N = 281) at enrollment in the REACH-OUT study (2010–2013). Treatment outcomes assessed at 1 year were discontinuation, and adherence, measured by proportion of days covered (PDC) or medication possession ratio (MPR). Remission status was assessed using the Structured Clinical Interview for Symptoms of Remission (SCI-SR). A machine learning platform, Reverse Engineering and Forward Simulation (REFS™), was used to identify predictors of study outcomes. Multivariate Cox and generalized linear regressions estimated the adjusted hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals.

          Results

          Among PP-N users, 27% discontinued their initial treatment regimen versus 51% ( p < 0.001) of OAT users. PP-N (vs OAT; HR = 0.49 [0.31–0.76]) users and males (HR = 0.65 [0.46–0.92]) had significantly lower rates of discontinuation. Relative to OAT, PP-N had a 36% [31%–42%] higher MPR and a 10-fold increased achievement of PDC ≥80% (OR = 10.46 [5.72–19.76]). PP users were significantly more likely to achieve remission in follow-up (PP-N vs OAT: OR = 2.65 [1.39–5.05]; PP-C vs OAT: OR = 1.83 [1.03–3.25]).

          Conclusions

          Relative to OAT, PP was associated with improved adherence, less frequent treatment discontinuation, and improved symptom remission in this CBHO study population.

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          Most cited references33

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          A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia.

          Data on the effectiveness of antipsychotics in the early phase of schizophrenia are limited. The authors examined the risk of rehospitalization and drug discontinuation in a nationwide cohort of 2,588 consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finland. The authors linked national databases of hospitalization, mortality, and antipsychotic prescriptions and computed hazard ratios, adjusting for the effects of sociodemographic and clinical variables, the temporal sequence of the antipsychotics used, and the choice of the initial antipsychotic for each patient. Of 2,588 patients, 1,507 (58.2%) collected a prescription for an antipsychotic during the first 30 days after hospital discharge, and 1,182 (45.7%, 95% confidence interval [CI]=43.7-47.6) continued their initial treatment for 30 days or longer. In a pairwise comparison between depot injections and their equivalent oral formulations, the risk of rehospitalization for patients receiving depot medications was about one-third of that for patients receiving oral medications (adjusted hazard ratio=0.36, 95% CI=0.17-0.75). Compared with oral risperidone, clozapine (adjusted hazard ratio=0.48, 95% CI=0.31-0.76) and olanzapine (adjusted hazard ratio=0.54, 95% CI=0.40-0.73) were each associated with a significantly lower rehospitalization risk. Use of any antipsychotic compared with no antipsychotic was associated with lower mortality (adjusted hazard ratio=0.45, 95% CI=0.31-0.67). In Finland, only a minority of patients adhere to their initial antipsychotic during the first 60 days after discharge from their first hospitalization for schizophrenia. Use of depot antipsychotics was associated with a significantly lower risk of rehospitalization than use of oral formulations of the same compounds. Among oral antipsychotics, clozapine and olanzapine were associated with more favorable outcomes. Use of any antipsychotic was associated with lower mortality.
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            The nature of relapse in schizophrenia

            Background Multiple relapses characterise the course of illness in most patients with schizophrenia, yet the nature of these episodes has not been extensively researched and clinicians may not always be aware of important implications. Methods We critically review selected literature regarding the nature and underlying neurobiology of relapse. Results Relapse rates are very high when treatment is discontinued, even after a single psychotic episode; a longer treatment period prior to discontinuation does not reduce the risk of relapse; many patients relapse soon after treatment reduction and discontinuation; transition from remission to relapse may be abrupt and with few or no early warning signs; once illness recurrence occurs symptoms rapidly return to levels similar to the initial psychotic episode; while most patients respond promptly to re-introduction of antipsychotic treatment after relapse, the response time is variable and notably, treatment failure appears to emerge in about 1 in 6 patients. These observations are consistent with contemporary thinking on the dopamine hypothesis, including the aberrant salience hypothesis. Conclusions Given the difficulties in identifying those at risk of relapse, the ineffectiveness of rescue medications in preventing full-blown psychotic recurrence and the potentially serious consequences, adherence and other factors predisposing to relapse should be a major focus of attention in managing schizophrenia. The place of antipsychotic treatment discontinuation in clinical practice and in placebo-controlled clinical trials needs to be carefully reconsidered.
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              Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia.

              The authors' goal was to evaluate the relationship between adherence to treatment with antipsychotic medication and health expenditures. A secondary objective was to identify risk factors predictive of nonadherence. Data included Medicaid eligibility and claims data from 1998 to 2000 for San Diego County, Calif. Pharmacy records were used to assess adherence to treatment with antipsychotic medication according to the cumulative possession ratio (the number of days medications were available for consumption divided by the number of days subjects were eligible for Medi-Cal). Regression models were used to examine risk factors, hospitalizations, and costs associated with nonadherence, partial adherence, adherence, and excess fills of antipsychotic medication. Forty-one percent of Medicaid beneficiaries with schizophrenia were found to be adherent to treatment with their antipsychotic medications: 24% were nonadherent, 16% were partially adherent, and 19% were excess fillers. Rates of psychiatric hospitalization were lower for those who were adherent (14%) than for those who were nonadherent (35%), partially adherent (24%), or had excess fills (25%). Rates of medical hospitalization were lower for those who were adherent (7%) than for those who were nonadherent (13%) or had excess fills (12%). Those who were adherent had significantly lower hospital costs than the other groups; pharmacy costs were higher among those who were adherent than among those who were nonadherent or partially adherent and were highest for excess fillers. Total costs for excess fillers (14,044 US dollars) were substantially higher than total costs for any other group. Despite the widespread use of atypical antipsychotic medications, alarmingly high rates of both underuse and excessive filling of antipsychotic prescriptions were found in Medicaid beneficiaries with schizophrenia. The high rates of antipsychotic nonadherence and associated negative consequences suggest interventions on multiple levels.
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                Author and article information

                Contributors
                janderson@gnshealthcare.com
                zicten@gnshealthcare.com
                707-953-0615 , veronica@gnshealthcare.com
                CBenson5@its.jnj.com
                kjoshi33@its.jnj.com
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central (London )
                1471-244X
                18 October 2017
                18 October 2017
                2017
                : 17
                : 346
                Affiliations
                [1 ]GRID grid.421702.2, GNS Healthcare, ; 196 Broadway, Cambridge, MA 02139-1902 USA
                [2 ]Janssen Scientific Affairs, 1125 Trenton Harbourton Rd, Titusville, NJ 08560 USA
                Article
                1507
                10.1186/s12888-017-1507-8
                5648472
                29047368
                9d9df4dd-58aa-43f4-bf04-29d816533d37
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 June 2016
                : 9 October 2017
                Funding
                Funded by: Janssen Scientific Affairs
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Clinical Psychology & Psychiatry
                paliperidone palmitate,oral antipsychotics,schizophrenia,adherence,remission,community behavioral health organization

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