Paliperidone Palmitate versus Risperidone Long-Acting Injection in Markedly-to-Severely Ill Schizophrenia Subjects

Fu, Dong-Jing; Bossie, Cynthia A.; Sliwa, Jennifer Kern; Ma, Yi-Wen; Alphs, Larry

doi:10.3371/csrp.fubo.022213

Cited by 9 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, the results demonstrated similar efficacy and safety outcomes when comparing PP to RLAI or oral paliperidone ER in patients with recently diagnosed schizophrenia, adult patients with chronic schizophrenia [20, 32, 36], and patients with markedly to severely ill schizophrenia [34]. However, in a 53-week RCT, PP was not as efficacious as RLAI, which may have been due to an inadequate initial dosing strategy, since modified [33].…”

Section: Specific Agentsmentioning

confidence: 98%

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Miyamoto

Fleischhacker

2017

Curr Treat Options Psych

View full text Add to dashboard Cite

Opinion StatementSchizophrenia is a mostly chronic mental disorder, and symptomatic relapse is frequently observed. It is often associated with social and/or occupational decline that can be difficult to reverse. Most patients with the illness need long-term pharmacological treatment, and antipsychotic drugs represent the mainstay of clinical care. Long-acting injectable antipsychotics (LAIs) are an important alternative to oral medication, particularly advantageous in the context of compliance management. Several new-generation antipsychotics (NGAs), including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting formulations, and new evidence has been accumulating. To date, all of the NGA LAIs have demonstrated a statistically and clinically significant decrease of relapse rates over placebo. The results of clinical trials comparing NGA LAIs with oral antipsychotics (OAPs) are not consistent, as being influenced considerably by study design. Superiority of LAIs to OAPs in efficacy is most evident in mirror image and cohort studies. New-generation LAIs are comparable to their oral mother compounds regarding safety and tolerability if one disregards potential injection site complications. There is little evidence of efficacy differences between the available LAIs, but they have different characteristics in terms of pharmacodynamic and pharmacokinetic profiles, injection interval, cost, requirements for oral supplementation, as well as adverse events. Considering these differences is useful for selecting LAIs for the treatment of individual patients. There is increasing evidence suggesting the use of LAIs in special patient groups, such as first-episode or forensic schizophrenia patients. This article reviews data on the use of NGA LAIs in schizophrenia and discusses current issues from clinical and methodological perspectives.

show abstract

Section: Specific Agentsmentioning

confidence: 98%

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Miyamoto

Fleischhacker

2017

Curr Treat Options Psych

View full text Add to dashboard Cite

show abstract

“…It was observed that the onset of response appeared to vary by symptom domain and may be partially driven by the change seen in uncontrolled hostility/excitement; a domain of the PANSS important for patient management (22). These results further support the relationship between PP1M plasma concentrations and onset of symptom control and efficacy (12,19). If a new paliperidone palmitate LAI formulation is developed with a different PK profile, it is possible that the time to observed efficacy would also be altered.…”

Section: Plasma Concentration and Therapeutic Effectmentioning

confidence: 66%

“…The relationship between symptom control and PK profile of PP1M has been demonstrated in two studies which compared the plasma concentration and efficacy in patients treated with PP1M or risperidone LAI (i.e. RISPERDAL CONSTA ® ) (12,19). A different initiation dosing regimen for PP1M was used in each study while the dose of risperidone LAI remained the same.…”

Section: Plasma Concentration and Therapeutic Effectmentioning

confidence: 99%

“…This supports an early onset of efficacy, without the need for oral supplementation. In contrast, the other long acting injectables risperidone (RISPERDAL CONSTA ® ) and aripiprazole (ABILIFY MAINTENA ® ) require supplementation with oral medications to attain efficacious plasma concentrations early in treatment (12).…”

Section: Plasma Concentration and Therapeutic Effectmentioning

confidence: 99%

“…The increase in paliperidone plasma concentrations over the first few days following administration is temporally related to the onset of efficacy, with continued improvement in symptoms over the following 2 to 3 weeks (12). The resulting relationship between the Canadian Reference Product PP1M formulation and therapeutic efficacy underlines the need to ensure that new formulations ("test" products) of paliperidone palmitate LAI products be therapeutically equivalent to the reference product, regardless of whether the new product is a subsequent-entry product ("generic product") or a first-entry ("branded product") undergoing a formulation change or a line extension.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Need for Bioequivalence Standards that Reflect the Clinical Importance of the Complex Pharmacokinetics of Paliperidone Palmitate Long-Acting Injectable Suspension

Procyshyn

Lamoure²,

Katzman

et al. 2019

J Pharm Pharm Sci

View full text Add to dashboard Cite

Paliperidone palmitate is a second generation antipsychotic, approved for the treatment of schizophrenia in the form of the long-acting injectable (LAI) products INVEGA SUSTENNA® (once monthly injection) and INVEGA TRINZA® (once every 3 months injection). Paliperidone palmitate dissolves slowly after deep intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The pharmacokinetic (PK) profile of the INVEGA SUSTENNA® formulation is biphasic, comprised of an initial relatively fast zero-order input, which allows rapid attainment of therapeutic concentrations without oral supplementation; and a subsequent maintained second-stage, first-order input, allowing for once monthly administration. Changes to the manufacturing processes can substantially alter the release characteristics of paliperidone palmitate LAI and consequently its PK profile. As an example, larger or smaller particle sizes of paliperidone palmitate can result in a delayed or accelerated release of paliperidone into the systemic circulation, respectively. Such changes are clinically relevant, as transient excursions above therapeutic plasma concentrations can be associated with an increased risk of adverse effects, including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms. Conversely, a delay in attaining therapeutic plasma concentrations of paliperidone on initiation of treatment, or a return to low plasma concentrations before the end of a dosing interval during repeated dosing, increases the risk of relapse. Given the integral relationship of the PK profile to the product’s clinical effects, it is important to have bioequivalence standards that reflect the complexity of the paliperidone palmitate LAI PK profile if one is to consider therapeutic equivalence based on simple bioequivalence testing. Although both the EMA and U.S. FDA have product-specific guidelines to determine bioequivalence, their requirements differ substantially. In Canada, no LAI product-specific bioequivalence guidance exists for multiphasic medication delivery systems, and the recently revised Comparative Bioavailability Standards: Formulations Used for Systemic Effects guidance applies only to oral and non-injectable formulations. We recommend that new Canadian standards be developed for multiphasic and biphasic intramuscular / subcutaneous (IM/SC) products, including paliperidone palmitate LAI products, because, similar to modified-release oral dosage forms, a different PK profile in modified-release IM/SC products can result in clinically meaningful differences in safety, efficacy, and tolerability. To ensure bioequivalence for both newly initiated and switch patients, this paper proposes bioequivalence standards that could be adopted in Canada that include two studies, a multiple-dose cross-over study, and a single-dose study with partial AUC metrics.

show abstract

Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia

et al. 2016

Self Cite

View full text Add to dashboard Cite

Objective. This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).Methods. PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.Results. Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.Conclusions. Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

show abstract

Paliperidone Palmitate versus Risperidone Long-Acting Injection in Markedly-to-Severely Ill Schizophrenia Subjects

Abstract: Using the recommended dosing regimens for PP and RLAI, both PP and oral risperidone (used during RLAI initiation) improved symptoms of schizophrenia in markedly-to-severely ill subjects at days 4-22.

Cited by 9 publications

References 24 publications

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Need for Bioequivalence Standards that Reflect the Clinical Importance of the Complex Pharmacokinetics of Paliperidone Palmitate Long-Acting Injectable Suspension

Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia

Contact Info

Product

Resources

About