Paliperidone Palmitate for Schizoaffective Disorder: A Review of the Clinical Evidence.
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ABSTRACT: Introduction
Despite being frequently diagnosed, there has been very limited study of efficacious treatments for schizoaffective disorder. Paliperidone had been approved for the treatment of schizoaffective disorder, and a recently completed relapse prevention study of the use of a once-monthly injectable paliperidone formulation has also led to an indication for that preparation to treat schizoaffective disorder.Methods
To review the efficacy and tolerability of paliperidone for schizoaffective disorder, we conducted a systematic literature search of studies of paliperidone in the treatment of schizoaffective disorder, and briefly reviewed evidence regarding the somewhat controversial nature of that diagnostic entity.Results
We located several studies of the use of paliperidone extended release in the treatment of schizoaffective disorder, but only one completed study of the use of paliperidone palmitate, which demonstrated efficacy in preventing relapse. Three other studies are currently recruiting participants. Efficacy and tolerability were similar to the profile of oral paliperidone in the treatment of individuals with schizophrenia. These results were similar for both individuals treated with paliperidone palmitate alone, and for those treated with paliperidone palmitate with adjunctive mood stabilizers and/or antidepressants. The use of paliperidone palmitate does not require initial co-administration of oral paliperidone, has relatively little risk of drug-drug interactions, and its pharmacokinetics are favorable for once-monthly administration, an important treatment option for individuals with psychotic disorders, who may often be non-adherent to effective medication regimens.Conclusion
Paliperidone palmitate is an approved treatment for schizoaffective disorder, and can be efficacious with or without commonly employed adjunctive treatments.
SUBMITTER: Greenberg WM
PROVIDER: S-EPMC4685865 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Data from a multiphase schizoaffective disorder study (NCT01193153) were used to examine the effects of paliperidone palmitate once-monthly (PP1M) by subjects' illness duration, defined as recent onset (≤5 years since first psychiatric diagnosis; n = 206) and chronic illness (>5 years; n = 461). Symptom and functioning scores, as measured during open-label PP1M acute and stabilization treatment phases, improved in both subpopulations, with greater improvements in recent onset than chronic illness subjects (p ≤ 0.022). Relapse rates, examined during the double-blind, placebo-controlled phase, were higher with placebo than PP1M: 30.0% vs. 10.2% (p = 0.014; hazard ratio [HR]: 2.8; 95% confidence interval [CI]: 1.11-7.12; p = 0.029) in the recent onset subpopulation and 35.5% vs. 18.1% (p = 0.001; HR: 2.38; 95% CI: 1.37-4.12; p = 0.002) in the chronic illness subpopulation. Growing evidence in the treatment of schizophrenia and schizoaffective disorder supports early intervention with long-acting antipsychotics.
| S-EPMC5380018 | biostudies-literature
Project description:IntroductionLong-acting injectable antipsychotic agents have been suggested to improve adherence and patient outcomes in schizophrenia or schizoaffective disorder. The purpose of this study was to assess medication use patterns (i.e., medication adherence, persistence), hospital and emergency department readmissions, and total direct medical costs of Oklahoma Medicaid members with schizophrenia or schizoaffective disorder switching from an oral antipsychotic (OAP) to once-monthly paliperidone palmitate (PP1M) or to another OAP (OAP-switch).MethodsA historical cohort analysis was conducted from 1 January 2016 to 31 December 2020 among adults aged ≥ 18 and ≤ 64 years with schizophrenia or schizoaffective disorder who were previously treated with an OAP. The first claim for PP1M or a new OAP defined the study index date. Members who transitioned from PP1M to 3-month formulation (PP3M) were included (i.e., PP1M/PP3M). Proportion of days covered (PDC), 45-day treatment gaps, 30-day readmissions to hospitals or emergency department, and total direct medical costs were assessed using multivariable, machine-learning least absolute shrinkage, and selection operator (Lasso) regressions controlling for numerous demographic, clinical, mental health, and provider characteristics.ResultsAmong 295 Medicaid members meeting full inclusion criteria, 183 involved PP1M/PP3Ms (44 PP1M cases transitioned to PP3M) and 112 involved an OAP-switch. The multivariable-adjusted odds of readmission were significantly associated with a 45-day treatment gap (p < 0.05) and non-adherence (i.e., PDC < 80%) (p < 0.05). Relative to PP1M/PP3Ms, the multivariable analyses also indicated that OAP-switch was associated with an 18.5% lower PDC, 92.3% higher number of 45-day treatment gaps, and an approximately 90% higher odds of all-cause 30-day readmission (p < 0.05). The adjusted pre- to post-index change in cost was approximately 49% lower for OAP-switches versus PP1M/PP3Ms (p < 0.001), although unadjusted post-index costs did not differ between groups (p = 0.440).ConclusionThis real-world investigation of adult Medicaid members with schizophrenia or schizoaffective disorder observed improved adherence and persistence with fewer readmissions with PP1M/PP3Ms versus OAP-switches.
| S-EPMC9643895 | biostudies-literature
Project description:Background and objectivesIdentifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia.MethodsAdults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score < 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition.ResultsOf 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, ZPANSS = -2.21, p = 0.028; ZCGI-S = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week 13 (OR = 1.11, 95% CI: 1.06, 1.17), and reduction of CGI-S score at week 13 (OR = 2.27, 95% CI: 1.03, 5.02).ConclusionA lower CGI-S total score at baseline and greater reductions in PANSS and CGI-S scores at week 13 were associated with patients achieving disease stabilization, that may allow for a successful transition. Evidence from this study indicates that better disease condition at baseline, early functional improvement and symptomatic relief were the key factors associated with disease stabilization. The findings may guide clinicians to identify suitable patients for transition from PP1M to PP3M and further optimize the use of PP3M in China.Clinical trials registrationEudraCT number: 2011-004889-15 and ClinicalTrials.gov (identifier: NCT01515423) for the original double-blind randomized study.
| S-EPMC10810987 | biostudies-literature
Project description:Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise and network meta-analysis that compared PP (25-150 mg equivalent) with paliperidone extended-release (PAL-ER, 3-12 mg/d) regarding their efficacy and safety in adults with acute symptoms of schizophrenia. The outcomes were the total score of the Positive and Negative Syndrome Scale (PANSS-T) at week 6 (the primary outcome for efficacy) and all-cause discontinuation(the primary outcome for acceptability), discontinuation due to inefficacy, discontinuation due to adverse events, discontinuation due to the withdrawal of consent, and the incidence of individual adverse events. Five studies on PP and seven studies on PAL-ER, which involved 4970 individuals in total, were included in this study. For the primary outcomes, we only included data from the treatment arms that used 100 or 150 mg equivalent as an initial dose of PP and data from the treatment arms that used 6, 9, or 12 mg as an initial dose of PAL-ER. The pairwise meta-analyses showed that both PP and PAL-ER outperformed placebo regarding PANSS-T at week 6 and all-cause discontinuation. However, there were no statistically significant differences in these outcomes between the effect sizes of PP and that of PAL-ER. Both PP and PAL-ER increased blood prolactin levels in both females and males compared with placebo. PAL-ER significantly increased blood prolactin in both females and males compared with PP. There were no statistically significant differences in other outcomes between the effect sizes of PP and that of PAL-ER. Similar results in all outcomes were observed in the network meta-analyses. In conclusion, PP might be a useful treatment option for adults with acute symptoms of schizophrenia. A noninferiority study that directly compares PP with PAL-ER for acute schizophrenia, conducted according to the recommended regimen, is required to provide solid evidence.
| S-EPMC9763417 | biostudies-literature
Project description:ImportanceLong-acting injectable antipsychotics are used to reduce medication nonadherence and relapse in schizophrenia-spectrum disorders. The relative effectiveness of long-acting injectable versions of second-generation and older antipsychotics has not been assessed.ObjectiveTo compare the effectiveness of the second-generation long-acting injectable antipsychotic paliperidone palmitate with the older long-acting injectable antipsychotic haloperidol decanoate.Design, setting, and participantsMultisite, double-blind, randomized clinical trial conducted from March 2011 to July 2013 at 22 US clinical research sites. Randomized patients (n = 311) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a long-acting injectable antipsychotic.InterventionsIntramuscular injections of haloperidol decanoate 25 to 200 mg or paliperidone palmitate 39 to 234 mg every month for as long as 24 months.Main outcome measuresEfficacy failure, defined as a psychiatric hospitalization, a need for crisis stabilization, a substantial increase in frequency of outpatient visits, a clinician's decision that oral antipsychotic could not be discontinued within 8 weeks after starting the long-acting injectable antipsychotics, or a clinician's decision to discontinue the assigned long-acting injectable due to inadequate therapeutic benefit. Key secondary outcomes were common adverse effects of antipsychotic medications.ResultsThere was no statistically significant difference in the rate of efficacy failure for paliperidone palmitate compared with haloperidol decanoate (adjusted hazard ratio, 0.98; 95% CI, 0.65-1.47). The number of participants who experienced efficacy failure was 49 (33.8%) in the paliperidone palmitate group and 47 (32.4%) in the haloperidol decanoate group. On average, participants in the paliperidone palmitate group gained weight and those in the haloperidol decanoate group lost weight; after 6 months, the least-squares mean weight change for those taking paliperidone palmitate was increased by 2.17 kg (95% CI, 1.25-3.09) and was decreased for those taking haloperidol decanoate (-0.96 kg; 95% CI, -1.88 to -0.04). Patients taking paliperidone palmitate had significantly higher maximum mean levels of serum prolactin (men, 34.56 µg/L [95% CI, 29.75-39.37] vs 15.41 µg/L [95% CI, 10.73-20.08]; P <.001, and for women, 75.19 [95% CI, 63.03-87.36] vs 26.84 [95% CI, 13.29-40.40]; P<.001). Patients taking haloperidol decanoate had significantly larger increases in global ratings of akathisia (0.73 [95% CI, 0.59-0.87] vs 0.45 [95% CI, 0.31-0.59]; P=.006).Conclusions and relevanceIn adults with schizophrenia or schizoaffective disorder, use of paliperidone palmitate vs haloperidol decanoate did not result in a statistically significant difference in efficacy failure, but was associated with more weight gain and greater increases in serum prolactin, whereas haloperidol decanoate was associated with more akathisia. However, the CIs do not rule out the possibility of a clinically meaningful advantage with paliperidone palmitate.Trial registrationclinicaltrials.gov Identifier: NCT01136772.
| S-EPMC4101890 | biostudies-literature
Project description:BackgroundPaliperidone palmitate is one of the most widely prescribed long-acting injectable (LAI) antipsychotics in the UK. However, it is relatively expensive and there are few data comparing its effectiveness to that of other LAI antipsychotics. We sought to address this issue by analyzing a large anonymized electronic health record (EHR) dataset from patients treated with LAI antipsychotics.MethodsEHR data were obtained from 1281 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who started treatment with a LAI antipsychotic between 1 April 2011 and 31 January 2015. The number of days spent as a psychiatric inpatient and the number of admissions to a psychiatric hospital were analyzed in each of the 3 years before and after LAI prescription.ResultsPatients treated with paliperidone palmitate (n = 430; 33.6%) had a greater number of inpatient days and a greater number of admissions in the year prior to treatment than those treated with other LAI antipsychotics. Nevertheless, in the 3 years after initiation there were no significant differences between paliperidone and the other LAI antipsychotics in the number of days as an inpatient (B coefficient 5.4 days, 95% confidence interval (CI) -57.3 to 68.2, p = 0.86) or number of hospital admissions (Incidence rate ratio 1.07, 95% CI 0.62 to 1.83, p = 0.82).ConclusionPaliperidone palmitate was more likely to be prescribed in patients with more frequent and lengthy hospital admissions prior to initiation. However, the absence of differences in outcomes after initiation indicates that paliperidone palmitate was not more effective than other cheaper LAI antipsychotics.
| S-EPMC6088783 | biostudies-literature
Project description:BackgroundTo obtain real-world evidence of functional improvements during atypical long-acting injectable (aLAI) therapy in recent-onset schizophrenia, an online survey was conducted to assess the impact of aripiprazole once-monthly injectable 400 mg (AOM 400; partial D2 receptor agonist) and paliperidone palmitate once-monthly (PP1M; injectable, full D2 receptor antagonist).MethodsPsychiatrists provided data for their 2 most recent AOM 400 patients, 2 most recent PP1M patients. Survey included 2000 patient cases (1000 AOM 400; 1000 PP1M). Eligible patients were aged 18-35 years, had been diagnosed with schizophrenia within 5 years, received AOM 400 or PP1M continuously for ≥6 months according to approved labels (mean durations: 1.6 and 1.7 years with AOM 400 and PP1M, respectively). Assessments included Global Assessment of Functioning (GAF) Scale, Personal and Social Performance Scale, Positive and Negative Syndrome Scale, and Quality of Life Scale. GAF assessments were done retrospectively and also at the time of survey.ResultsBaseline mean GAF scores were 43.3 and 43.8 for AOM 400 and PP1M, respectively, indicating serious symptoms/functional impairment in both groups. Mean improvements following AOM 400 and PP1M therapy were 19.7 and 16.3 points, respectively (final scores in mild functional impairment category). Other measures assessing symptoms/functionality/quality of life demonstrated the benefits of long-term aLAI therapy.ConclusionSchizophrenia patients with serious functional impairment prior to current aLAI treatment showed improvements in functional outcome after AOM 400 or PP1M therapy. These results suggest functional improvements with aLAIs are apparent not only in research but also real-world settings.
| S-EPMC8203189 | biostudies-literature
Project description:PURPOSE:Reducing the dosing frequency of antipsychotics (APs) with long-acting injectables (LAIs) such as once-monthly paliperidone palmitate (PP1M) can improve adherence and clinical outcomes for schizophrenia patients. This US study compared physical and psychiatric comorbidity-related outcomes, AP adherence, healthcare resource utilization (HRU), and costs pre- and post-transition to PP1M among schizophrenia patients treated with oral risperidone/paliperidone pre-PP1M transition. METHODS:Health insurance claims from the IQVIA™ PharMetrics Plus database (01/01/2012-07/31/2018) were used to identify adults with???2 schizophrenia diagnoses,???1 claim for PP1M, and???30 days of treatment with oral risperidone/paliperidone in the 60 days before the first PP1M claim (i.e., the index date). Comorbidity-related outcomes, adherence to APs (measured via the proportion of days covered [PDC]), all-cause per-patient-per-month (PPPM) HRU, and all-cause PPPM medical, pharmacy, and total costs (i.e., sum of medical and pharmacy costs) during the 6-month periods pre- and post-transition to PP1M were compared using generalized estimating equation models adjusted for repeated measurements. Analyses were replicated in the subset of patients with???1 all-cause inpatient stay pre-PP1M transition. FINDINGS:Among 427 schizophrenia patients transitioning from oral risperidone/paliperidone to PP1M, the mean age was 41.1 years and 37.9% were female. Following the PP1M transition, patients were less likely to have claims with a diagnosis for psychoses (odds ratio [OR] 0.41; P?<?0.001), hypertension (OR 0.80; P?=?0.011), depression (OR 0.70; P?<?0.001), drug abuse (OR 0.60; P?<?0.001), substance-related and addictive disorders (OR 0.73; P?=?0.003), bipolar and related disorders (OR 0.59; P?<?0.001), sleep-wake disorders (OR 0.68; P?=?0.017), anxiety disorders (OR 0.78; P?=?0.034), and other conditions that may require a focus of clinical attention (OR 0.58; P?<?0.001). Mean PDC by APs was higher post-PP1M (mean?=?0.81) versus pre-PP1M (mean?=?0.68) transition. Post-PP1M, patients were less likely to have an all-cause emergency room visit (OR 0.51; P?<?0.001) or inpatient stay (OR 0.39; P?<?0.001) compared to pre-PP1M. All-cause total healthcare costs remained similar post- versus pre-transition to PP1M (mean monthly cost difference [MMCD]?=?$228; P?=?0.260). Pharmacy costs increased post-PP1M (MMCD?=?$960; P?<?0.001), but were offset by decreasing medical costs (MMCD?=?- $732; P?<?0.001), largely driven by lower costs related to inpatient stays (MMCD?=?- $695; P?<?0.001) and emergency room visits (MMCD?=?- $63; P?<?0.001). For patients with???1 all-cause inpatient stay pre-PP1M transition (N?=?177), a more pronounced improvement in comorbidity-related outcomes, a more pronounced reduction in HRU, and a reduction in total healthcare costs (MMCD?=?- $1308; P?<?0.001) were observed post-transition to PP1M. IMPLICATIONS:Among schizophrenia patients in the US, transitioning to PP1M following oral risperidone/paliperidone treatment was associated with improved comorbidity-related outcomes, higher adherence, and a reduction in HRU, while remaining cost neutral. Furthermore, patients with???1 all-cause inpatient stay pre-PP1M transition had significantly lower total healthcare costs post-PP1M transition.
| S-EPMC7061019 | biostudies-literature
Project description:BackgroundThe utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice.MethodsA systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis.ResultsEleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements.ConclusionOur findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.
| S-EPMC10799459 | biostudies-literature
Project description:AimThis post hoc analysis of a double-blind (DB), randomized, placebo-controlled, relapse-prevention study evaluated the effects of paliperidone palmitate once-every-3-months (PP3M) in a subpopulation of adults with early illness schizophrenia (duration ≤5 years) from a clinical trial.MethodsPatients received either PP3M or placebo every 3 months in the DB phase. The primary efficacy variable was time from randomization to first relapse. Symptom severity, patient functioning, and safety were also assessed.ResultsA total of 119 patients who entered the DB phase met the criteria for early illness schizophrenia (PP3M, n = 62; placebo, n = 57). PP3M significantly delayed time to relapse vs placebo (P = .035; hazard ratio, 3.08; 95% CI, 1.08-8.80). Symptomatic control and patient functioning were maintained in the PP3M group but significantly worsened in the placebo group. There were no unexpected tolerability findings.ConclusionsPP3M reduced relapse risk and maintained symptomatic and functional improvements compared with placebo in patients with early illness schizophrenia.
| S-EPMC6585630 | biostudies-literature