Tolerability Of Paliperidone Palmitate Research Articles

The Switch From Paliperidone Long-Acting Injectable 1- to 3-Monthly: Clinical Pharmacokinetic Evaluation in Patients With Schizophrenia (Preliminary Data).

The aim of the study was a preliminary evaluation of the maintenance of clinical efficacy and tolerability of paliperidone palmitate in patients with schizophrenia during the transition phase from 1-monthly paliperidone palmitate formulation (PP1M) to PP3M, with the evaluation of plasma levels of the drug. A prospective observational study was conducted for 13 months involving 22 outpatients, aged 18 to 66 years and clinically stabilized. Patients were affected by schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. For each patient, clinical assessment, safety and tolerability, and drug plasma level determination were performed. Clinical efficacy was assessed by Brief Psychiatric Rating Scale, Positive and Negative Symptom Scale, and Hamilton Rating Scale for Depression. During the first 4 months of the study, once-monthly paliperidone palmitate was administered, and then during the following 9 months, the 3-monthly formulation was administered. The time course of the Brief Psychiatric Rating Scale total scores showed a statistically significant (P = 0.006) improvement from T0 to T8; Positive and Negative Symptom Scale scores showed a similar time course, with a statistically significant (P = 0.0016) reduction of the mean total score; Hamilton Rating Scale for Depression mean scores showed a statistically significant (P = 0.003) reduction with substantial maintenance of clinical stabilization of the patients. Only 1 patient dropped out after the first PP3M injection. Our preliminary data currently confirm the maintenance of clinical stability shifting from PP1M to PP3M.

Paliperidone LAI and Aripiprazole LAI Plasma Level Monitoring in the Prophylaxis of Bipolar Disorder Type I with Manic Predominance.

The objective of this study was the evaluation of utility of plasma level monitoring in the clinical stabilizing efficacy and tolerability of paliperidone palmitate (PP) vs. aripiprazole monohydrate (AM) in bipolar disorder I (BD I) with manic predominance. Fifty-six outpatients of both sexes, age ranging from 18 to 65 years, affected by BD I with manic predominance, orally treated and stabilized after acute episode for at least 2 weeks with paliperidone or aripiprazole (n=31, paliperidone; n=25, aripiprazole) underwent a prospective observational study of switching to the corresponding long-acting injection (LAI) on the basis of clinical evaluation. The efficacy and tolerability of the 2 treatments were assessed by BPRS, PANSS, HAMD21, and MRS rating scales and a check list every month for 12 months. Drug plasma levels determinations (PLs) were performed at the same times. A good clinical stability and tolerability of both drugs were reported. Lower mean PLs of PP showed a positive effect on depressive symptoms. AM PLs variability was associated with greater instability of manic symptoms whereas intermediate PLs seem to have more influence on depressive symptomatology. PLs drug monitoring has been proven to be useful, and further investigations to identify optimal therapeutic ranges for LAI formulations are needed.

Paliperidone palmitate in short- and long-term treatment of schizophrenia.

Poor adherence to treatment remains a major problem in the management of patients with schizophrenia. In the 60s, first generation antipsychotics in depot formulation have been introduced on the market with the aim to improve adherence to therapy. However, the limited effectiveness on negative symptoms and the tendency to induce extrapyramidal side effects has limited their use. Currently there are five second-generation antipsychotic long-acting formulations and the use of these drugs has definitely changed perspective: they are no more restricted as compounds intended to improve compliance, but they can be considered first-line drugs with proven efficacy and good tolerability. In this narrative review the efficacy and tolerability of paliperidone palmitate, as well as the economic impact of the use of this particular molecule, have been evaluated in the short- and long-term treatment of schizophrenia. Taking into account the results of different studies, paliperidone, especially in his long-acting formulation, can be considered a viable and effective treatment for patients with schizophrenia, both in the short- and in the long term.

Can drug interaction be useful? Case report of a schizophrenic patient treated with paliperidone long-acting injection

IntroductionIntramuscular paliperidone palmitate (PLAI) is a long-acting atypical anti-psychotic approved in Romania for the maintenance treatment of adults with schizophrenia.ObjectivesTo determine the efficacy and tolerability of PLAI in a non-compliant patient with previously very low tolerability to oral anti-psychotics. The patient had been on risperidone long acting injection (RLAI) and had significant adverse events (i.e. tremor, akatisia) which persisted even when treated with the lowest dose of PLAI: 50 mg.AimsSince the efficacy of PLAI was good, and since a lower dose (than 50 mg of PLAI) is not available in Romania, we tried different ways to lower plasma concentration (PC) of the anti-psychotic because the patient presented clinically significant adverse effects (AE).MethodsInitially the time between the injections was extended at maximum recommended (35 days), with a slight effect, then an off label treatment was associated in order to lower the PC of PLAI. We used 300 mg of carbamazepine long acting, that may lower the PC of PLAI up to 30%. For the evaluation of the efficacy and tolerability, we applied: the clinical evaluation, the positive and negative syndrome scale, the Barnes Akathisia rating scale, the Simpson-Angus Scale and the abnormal involuntary movement scale.ResultsAfter using the above mentioned, strategies, the one that had indeed good results on reducing AE, with no alteration of the psychic status of the patient, was the association of carbamazepine.ConclusionsIn clinical practice, some off label medication associations may be salutary!Disclosure of interestThe authors have not supplied their declaration of competing interest.

Paliperidone palmitate: effectiveness, safety, and the use for treatment of schizophrenia.

The aim of the study was to summarize the efficacy and tolerability of paliperidone palmitate, an atypical long-acting antipsychotic drug. Paliperidone is a 9-hydroxy metabolite of risperidone with a slightly different receptor profile and significantly different pharmacokinetic profile. After the short review of its pharmacological properties, the efficacy of the drug in comparison to placebo or to an active comparator was described. The studies revealed the effectiveness of paliperidone palmitate in the treatment of psychotic symptoms, mainly schizophrenia. The drug proved to be efficacious in both acute psychotic symptoms treatment and long-term treatment. Its efficacy in patients with schizophrenia was similar and sometimes even better than the efficacy of other long-acting drugs, such as risperidone or olanzapine. In the pharmacoeconomic studies, paliperidone proved to be cost-effective in comparison to risperidone or olanzapine. The review of the literature also underlined that paliperidone palmitate is well tolerated, compared with placebo. Frequency and severity of side-effects such as extrapyramidal symptoms, hyperprolactinemia and weight gain, was similar or less than those found in treatment with other atypical antipsychotics, including long-acting ones.

A “Newly Discovered in Romania” atypical antipsychotic prolonged release treatment for patient with schizophrenia. First results of a naturalistic study with recently approved paliperidone palmitate

IntroductionIntramuscular paliperidone palmitate is a long-acting atypical antipsychotic, which has only been marketed in Romania from march 2015 as a free of charge medication/subsidized for the acute and maintenance treatment of schizophrenia in adults.Objectives and aimsTo determine the efficacy and tolerability of paliperidone palmitate in 12 patients with schizophrenia in an outpatient care unit, taking into account the limited clinical experience with this product in Romania.MethodsThe study was performed in an outpatient care unit. Data was collected from medical records of patients started on paliperidone palmitate between March and June 2015. This time period was selected because we wanted to have at least a 6-month period of evaluating these patients. Some of the patients were previously on risperidone long-acting injection (in Romania the advantages of a 1-month injection instead of 2 and the fact that the medication does not need to be held in a refrigerator are 2 important factors that can increase the compliance of the patients). Others were treated with other long-acting antipsychotics (flupentixol). The rest were patients treated before with risperidone, with good response, but with problems of non-compliance.ResultsNone of the patients treated with paliperidone palmitate relapsed. Some of them had, at maximum dose, minor extrapyramidal symptoms that disappeared when we lowered the dose. Taking into account the lack of insight and the non-compliance of patients with schizophrenia, this treatment seems to be extremely valuable, maybe more in this kind of cases, in outpatient care units.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Real-world paliperidone palmitate data from acute units: The SHADOW study

IntroductionThere is an increasing interest in understanding how antipsychotic treatments work in a real-world-setting. This is especially important with long-acting-antipsychotics, where explanatory trials may not always represent the real-world-population. Observational studies and pragmatic-clinical trials could provide additional information about new therapies, which could inform decision-making processes.ObjectivesTo assess the effectiveness of Paliperidone-Palmitate(PP) in an acute setting within real-world-conditions. Functionality, satisfaction with treatment and pattern of use were also evaluated.MethodsAn observational, prospective 6-week follow-up study was performed in acute units including adult patients with acute exacerbation of schizophrenia that started treatment with PP. Data were collected from initiation of PP until week-6 (or patient's discharge if earlier). Clinical-Global Inventory-Severity (CGI-S) was used to assess effectiveness as well as changes in illness severity. Other outcomes included total score on the Personal and Social Performance scale (PSP), patient-satisfaction with medication (MSQ) and tolerability. Student's-t tests were used to assess changes from baseline in CGI-S and PSP.ResultsTwo hundred and eighty patients were included in the analysis (mean age: 40.5 ± 12.2 [SD] years). A significant decrease in mean (SD) CGI-S score between baseline (4.7 [0.9]) and endpoint (3.3 [0.9]) (P < 0.0001) was observed. (Note that 21% of patients were discharged on PP-monotherapy). Patient-functioning also significantly improved from baseline to endpoint (P < 0.0001). Seventy-four percent of patients were satisfied (measured by MSQ) at the end of follow-up. Anticholinergic-treatment was less frequent for PP discharged on monotherapy vs. not monotherapy (12.5% vs 21.2% respectively). Overall, PP was well-tolerated. Twenty-five AEs were reported in 20 patients (incidence 7.1%). No serious AEs occurred.ConclusionsThese results support the effectiveness and tolerability of PP in an acute setting under daily-clinical-practice with good acceptance by patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Efficacy and safety of once-monthly injection of paliperidone palmitate in hospitalized Asian patients with acute exacerbated schizophrenia: an open-label, prospective, noncomparative study.

IntroductionThis single-group, open-label, prospective, noncomparative, multicenter, Phase IV study explored the efficacy and tolerability of paliperidone palmitate (PP) in hospitalized patients with acute exacerbation of schizophrenia.MethodsAsian patients of either sex, between 18 and 65 years of age, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) with acute exacerbations within the previous 4 weeks, were enrolled. Intramuscular PP was initiated at doses of 150 milligram equivalent (mg eq) (day 1) and 100 mg eq (day 8), followed by a monthly maintenance dose between 75 mg eq and 150 mg eq (days 36 and 64). Primary efficacy endpoint was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score (last-observation-carried-forward) at week 13.ResultsOf the 212 enrolled patients, 152 (71.7%) completed the 13-week treatment; withdrawal of consent (24 [11.3%] patients) was the most common reason for study discontinuation. Mean (standard deviation) PANSS total score from baseline (90.0 [17.41]) improved significantly at day 4 (−6.1 [9.27]; 95% confidence interval: −7.38, −4.85; P<0.001) and week 13 endpoint (−23.9 [23.24]; 95% confidence interval: −27.10, −20.78; P<0.001). Similarly, the secondary endpoints (Clinical Global Impression-Severity, Physical and Social Performance, each PANSS subscale, and Marder factor scores) improved significantly from baseline to week 13 endpoint (P<0.001 for all). At week 13, 112/210 (53.3%) patients had a 40% improvement in the PANSS total score (responder rate), and 133/212 (62.7%) patients were ready for hospital discharge. Overall, 139 (65.6%) patients experienced at least one treatment-emergent adverse event (TEAE). Most common (>5%) TEAEs were hyperprolactinemia, constipation, nasopharyngitis, insomnia, increased weight, and tremor. Worsening of schizophrenia (3.3%) and sinus bradycardia (2.0%) were serious TEAEs; no deaths were reported.ConclusionPP was generally tolerable and efficacious in a hospital setting for the treatment of acute exacerbated schizophrenia with significant improvements in psychotic symptoms, social functioning, and severity of illness.

Efficacy and safety of flexibly dosed paliperidone palmitate in Chinese patients with acute schizophrenia: an open-label, single-arm, prospective, interventional study.

This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75–150 mg eq, deltoid/gluteal injection) in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70), who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period). Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions–Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2%) completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years). Total, 443/610 (72.6%, full analysis set) patients achieved primary endpoint (mean [standard deviation] change from baseline: –30.9 [19.51]). All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5%) treatment-emergent adverse events were extrapyramidal disorders (8.4%). The efficacy and safety data are consistent with other short-term, placebo-controlled studies of paliperidone palmitate conducted in similar populations.

A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia

The safety and tolerability of paliperidone palmitate, an injectable atypical antipsychotic agent, were assessed in a 1-year open-label extension of a double-blind study in patients with schizophrenia. Patients from the double-blind study who experienced a recurrence, remained recurrence free until study end, or who were in the transition, maintenance or double-blind phases and had received at least one injection of paliperidone palmitate when enrollment was stopped, were eligible for the open-label extension. Patients received gluteal injections of paliperidone palmitate once every 4 weeks: starting dose 50 mg eq. followed by 25, 50, 75, or 100 mg eq. flexible dosing. Of the 388 patients enrolled, 288 completed the open-label extension. During the open-label extension, the median (range) duration of exposure to paliperidone palmitate was 338 days (10; 390), and 74% of patients received all 12 open-label injections of paliperidone palmitate. The most frequent (≥ 5% in total group) adverse events were insomnia (7%); worsening of schizophrenia; nasopharyngitis; headache; and weight increase (6% each). Potentially prolactin-related adverse events occurred in 13 (3%) patients, mostly women, and none resulted in study discontinuation. Extrapyramidal treatment-emergent adverse events were reported in 25 (6%) patients; tremor was the most frequently reported (n = 8, 2%). At open-label extension endpoint, investigator-rated redness at the injection site was observed in ≤ 4% of patients in each group. Injection-site pain was rated by investigators as absent in 82-87% of patients. Schizophrenia symptoms measured by Positive and Negative Syndrome Scale and personal and social performance changes improved during the open-label extension.