Oral Paliperidone Research Articles

Antipsychotic Management of Schizoaffective Disorder: A Review.

Schizoaffective disorder (SAD) is an incapacitating illness that presents clinicians with challenges in terms of both its diagnosis and its psychopharmacological management. Most studies conducted on the psychopharmacological treatment of SAD also include patients with schizophrenia or other psychotic illnesses, thereby providing an unspecific view to the clinician as to the best way of treating patients with SAD. The objective of this article is to review studies on evidence-based treatment of patients with SAD. We conducted a systematic literature search in MEDLINE/PubMed for full-text studies in the English language using the terms 'Schizoaffective and treatment' or 'antipsychotic schizoaffective'. Our review found relatively few studies with either an active comparator or placebo that examined the efficacy of antipsychotics for patients with SAD without an admixture of patients with schizophrenia. Only oral paliperidone extended release (ER), paliperidone long-acting injection (LAI), and risperidone have been shown to be effective and safe in reducing psychotic as well as affective components in acutely ill SAD patients in controlled studies. Paliperidone ER and LAI have also been shown to be efficacious in the maintenance treatment phase of SAD patients. While no supportive data exist, it is possible that other atypical antipsychotics may have similar efficacy to the two mentioned above. We conclude with a number of research recommendations for the study of treatment options for patients with SAD. First, there is a need for studies with patients specifically diagnosed with SAD for both the acute and the maintenance phase. The sample size needs to be adequate to allow a primary analysis of efficacy and to allow for analysis of the SAD subtypes: depressed and bipolar. Another recommendation is the need for studies of patients with SAD stratified into patients with and without mood stabilizers or antidepressants to allow the examination of the adjunctive role of these psychotropic medications. A third recommendation is to focus on specific co-morbid aspects of patients with SAD, such as suicidality and substance use disorders. Data from such studies will fill the gap of evidence-based treatment approaches and help clinicians in making important treatment decisions for patients with this complex condition.

A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder.

Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55–3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI formulation, there is the advantage of improved adherence and simplified treatment in the long-term management of SCA.

Dyskinesia, cardiac arrhythmia and partial seizure associated with paliperidone overdose: a case report

Paliperidone is a new atypical antipsychotic agent. There are few literature reports of paliperidone overdoses and we report a case of these. A 32-year-old man was admitted to Emergency Department for occurrence of opisthotonus, muscular spasms and rigidity. Twenty hours before, he had an ingestion of 168 mg of paliperidone. He had hypotension and tachycardia. The dystonic reaction completely resolved within a few minutes after diazepam. Nine hours after admission, he sudden showed a right hemisoma partial seizure. The peculiar interest of our case is that three different and rare symptoms occurred in successive times after overdose. Some symptoms occurred after several hours following overdose. Oral paliperidone is available as an &lt;em&gt;osmotic release delivery system&lt;/em&gt; that results in a gradual rise in plasma concentrations. According to this limited experience in which delayed onset of toxicity has been observed, it may be prudent to recommend prolonged observation after overdose of paliperidone.

De novo cost-utility analysis of oral paliperidone in the treatment of schizoaffective disorder

ObjectivesThe aim of this analysis is to compare costs and effectiveness of paliperidone ER vs. placebo in the treatment of schizoaffective disorder (SAD) in the Czech Republic based on pooled clinical trial data. MethodsA de novo micro-simulation model was developed to assess the cost-utility analysis of paliperidone vs. placebo as there is lack of clinical data comparing paliperidone to other interventions. There are no studies primarily evaluating the efficacy of treatment of SAD with other antipsychotics. The model estimated effectiveness and costs of patients with SAD every week during 24-week time horizon. The effectiveness was defined as improvement of a patient's PANSS score where utilities were assigned to each modelled PANSS score. Based on the patient level data a linear mixed-effects model was used to estimate the regression equations of percentage decrease of PANSS score from the baseline. Utilities were computed using a regression function of patients' age, sex and PANSS score, which was adapted from a clinical study of patients with schizophrenia as there are no QoL data on SAD patients. Among relevant costs, reflecting the payer's perspective, costs of pharmacotherapy, concomitant medications and outpatient care were considered. ResultsThe average ICER of paliperidone compared to placebo reached 28,935 EUR/QALY. The probability of paliperidone being cost-effective compared to placebo was 99.5%. ConclusionsTreatment of SAD with paliperidone results in acceptable ICER and high probability of being cost-effective compared to placebo. Thus, it can be considered as a cost-effective treatment of patients with SAD in the Czech Republic.

Paliperidone Palmitate for Schizoaffective Disorder: A Review of the Clinical Evidence.

IntroductionDespite 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.MethodsTo 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.ResultsWe 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.ConclusionPaliperidone palmitate is an approved treatment for schizoaffective disorder, and can be efficacious with or without commonly employed adjunctive treatments.Electronic supplementary materialThe online version of this article (doi:10.1007/s40120-015-0030-4) contains supplementary material, which is available to authorized users.

Treatment response, safety, and tolerability of paliperidone extended release treatment in patients recently diagnosed with schizophrenia.

Objective:This study was designed to explore the efficacy and tolerability of oral paliperidone extended release (ER) in a sample of patients who were switched to flexible doses within the crucial first 5 years after receiving a diagnosis of schizophrenia.Methods:Patients were recruited from 23 countries. Adults with nonacute but symptomatic schizophrenia, previously unsuccessfully treated with other oral antipsychotics, were transitioned to paliperidone ER (3–12 mg/day) and prospectively treated for up to 6 months. The primary efficacy outcome for patients switching for the main reason of lack of efficacy with their previous antipsychotic was at least 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores. For patients switching for other main reasons, such as lack of tolerability, compliance or ‘other’, the primary outcome was non-inferiority in efficacy compared with the previous oral antipsychotic.Results:For patients switching for the main reason of lack of efficacy, 63.1% achieved an improvement of at least 20% in PANSS total scores from baseline to endpoint. For each reason for switching other than lack of efficacy, efficacy maintenance after switching to paliperidone ER was confirmed. Statistically significant improvement in patient functioning from baseline to endpoint, as assessed by the Personal and Social Performance scale, was observed (p < 0.0001). Treatment satisfaction with prior antipsychotic treatment at baseline was rated ‘good’ to ‘very good’ by 16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone ER. Paliperidone ER was generally well tolerated, with frequently reported treatment-emergent adverse events being insomnia, anxiety and somnolence.Conclusions:Flexibly dosed paliperidone ER was associated with clinically relevant symptomatic and functional improvement in recently diagnosed patients with non-acute schizophrenia previously unsuccessfully treated with other oral antipsychotics.

Antipsychotic Treatment in Pluripathology

Is well known some organic diseases produce psychotic symptoms. Association between HIV and presence of psychopathology is highly prevalent. For this reason, a case report of HIV, liver cirrhosis, drug abuse and psychotic disorder is presented below. The patient was a 46 year old male infected by HIV and liver cirrhosis (Child-Pugh B) secondary to HCV infection. He had had psychiatric history of major depressive disorder, cannabis use disorder, alcohol use disorder, cocaine use disorder and heroin use disorder. Without consume of heroin, cocaine and alcohol during last 5 years. He was in treatment with methadone, benzodiazepines and antiretroviral treatment. In 2013 the patient suffered a psychotic episode with an important affective and behavioral repercussion and he was admitted in an acute unit of psychiatry. It was necessary a pharmacological treatment with a limited hepatic metabolism because of his liver cirrhosis and potential drug interactions with antiretroviral treatment and methadone. So that, it was decided to use oral Paliperidone (9 mg/day), achieving a remission of psychotic symptomatology. In this case Paliperidone was safe, without side effects and good tolerance. Liver function was preserved and CD4 levels remained undetectable. In patients with severe mental illness and concomitant organic disease, complexity of treatment is a determining factor in therapeutic decisions. In conclusion, Paliperidone could be considered sure to treat psychotic symptoms in schizophrenic patients who use others medications with hepatic metabolism, drug interactions, and mild to moderate liver failure.

Tolerability of Paliperidone in Inpatients

Introduction As we know antipsychotic drugs are associated with the presence of side effects thar impair adherence, the course of the disease and the patient's functionality. Besides drug efficacy, tolerability is a factor which we consider in the choice of treatment. Materials and Methods Descriptive cross-sectional study of inpatients between June and September 2014 in treatment with paliperidone and with any psychiatric diagnosis according to the diagnostic criteria Statistical Manual of Mental Disorders (DSM-IV). To evaluate the presence of side effects we use the UKU (Udvalg fur Kliniske Undersogelser), which is a comprehensive measure of side effects of psychotropic drugs. It consist of 54 items grouped into psychological, neurological, autonomic and other symptoms. Results 18 patients (12 men and 6 women) were included. The average age was 37 years. 16 patients (88.8%) had a diagnosis of Tr. psychotic and 2 of them (11.1%) Tr. personality. 8 patients had started treatment with oral paliperdione two weeks before evaluation, while the remaining 10 patients had longer treatment (mean 9.4 months). Symptoms found in the psychic area were astenia, lassitude, fatigability, decreased sleep duration and emotional indifference. No symptoms were described in the neurological area. Among the autonomic effects: increased sweating and inside the area “others”: decreased sexual desire, erectile dysfunction and weight loss. All of them were obtained as slight maximum score. Conclusions These data give us guidance on the tolerability profile of oral paliperidone short to medium term. The values obtained in the UKU scale indicate good tolerability of the treatment.

Manic Symptoms during a Switch from Paliperidone ER to Paliperidone Palmitate in a Patient with Schizophrenia.

Some antipsychotic drugs have treatment efficacy for mania and bipolar disorder. However, these drugs may rarely cause manic symptoms in some schizophrenic patients. We hereby report a 22-year-old female patient with schizophrenia who experienced a manic episode during a switch from paliperidone ER to paliperidone palmitate. This case is an important reminder that an abrupt switch from oral paliperidone to paliperidone palmitate may predispose certain patients to hypomanic or manic symptoms.

Flexible-dose oral paliperidone ER in non-acute schizophrenia previously unsuccessfully treated with oral risperidone

Aims: Assessment of oral paliperidone ER therapy. Methods: A subgroup analysis of patients with schizophrenia switched from unsuccessful oral risperidone therapy in a 6-month, open-label, multicenter study investigating flexibly dosed paliperidone ER. Results: 694 patients were analyzed (59.2% male; mean age: 40.0 years). Mean change in PANSS total score from baseline to end point was -14.4 ± 20.2 in patients switching due to lack of efficacy (n = 359). Mean change in PANSS total score for patients switching for other reasons (n = 319) was: -7.6 ± 17.0 (lack of tolerability, n = 175), -19.6 ± 20.3 (lack of compliance, n = 76), and -12.0 ± 16.8 (other, n = 68). Conclusion: In patients with schizophrenia previously unsuccessfully treated with oral risperidone, paliperidone ER was well tolerated and associated with a meaningful treatment response.

Incidence of tardive dyskinesia: a comparison of long-acting injectable and oral paliperidone clinical trial databases.

BackgroundTo assess the tardive dyskinesia (TD) rate in studies of once-monthly long-acting injectable (LAI) paliperidone palmitate (PP) and once-daily oral paliperidone extended release (Pali ER).MethodsCompleted schizophrenia and bipolar studies for PP and Pali ER (≥ 6 month duration with retrievable patient-level data) were included in this post hoc analysis. Schooler–Kane research criteria were applied using Abnormal Involuntary Movement Scale (AIMS) scores to categorise probable (qualifying AIMS scores persisting for ≥ 3 months) and persistent TD (score persisting ≥ 6 months). Spontaneously reported TD adverse events (AEs) were also summarised. Impact of exposure duration on dyskinesia (defined as AIMS total score ≥ 3) was assessed by summarising the monthly dyskinesia rate.ResultsIn the schizophrenia studies, TD rates for PP (four studies, N = 1689) vs. Pali ER (five studies, N = 2054), were: spontaneously reported AE, 0.18% (PP) vs. 0.10% (Pali ER); probable TD, 0.12% (PP) vs. 0.19% (Pali ER) and persistent TD, 0.12% (PP) vs. 0.05% (Pali ER). In the only bipolar study identified [Pali ER (N = 614)], TD rate was zero (spontaneously reported AE reporting, probable and persistent TD assessments). Dyskinesia rate was higher within the first month of treatment with both PP (13.1%) and Pali ER (11.7%) and steadily decreased over time (months 6–7: PP: 5.4%; Pali ER: 6.4%). Mean exposure: PP, 279.6 days; Pali ER, 187.2 days.ConclusionsRisk of TD with paliperidone was low (< 0.2%), regardless of the formulation (oral or LAI), in this clinical trial dataset. Longer cumulative exposure does not appear to increase the risk of dyskinesias.

Cost-Utility Analysis of Long-Acting Paliperidone in Comparison with Oral Risperidone, Oral Paliperidone and Long-Acting Risperidone in the Maintenance Treatment of Schizophrenia in the Czech Republic.

The number of patients with schizofrenia in the Czech Republic amounts annually to approximately 126,000. Schizophrenia causes significant increases in mortality, shortening life expectancy by 25 years compared to the general population which implies high disease burden. The aim was to estimate the cost-effectiveness of long-acting paliperidone in the treatment with schizofrenia compared to oral risperidone, oral paliperidone and long-acting risperidone. Cost-utility analysis was performed using a Markov model. The primary outcome was ICER/QALY. Oral risperidone, oral paliperidone and long-acting risperidone were selected as comparators. The basic components of the model include probabilities of relapse, individual hazard ratios for non-compliance by medication type and switch of treatment probabilities. Specific utilities for each health state were considered. Among relevant costs, reflecting payer's perspective, drug acquisition costs, monitoring costs, costs of relapses, follow-up care and adverse events were considered. Long-acting paliperidone reached ICER of EUR 16,233/QALY compared to oral risperidone, EUR 15,058/QALY to oral paliperidone and EUR 335/QALY to long-acting risperidone. The robustness of the model was supported by one-way deterministic analysis and probabilistic sensitivity analysis, which gave stable Results. Long-acting paliperidone was cost effective in 97% of the simulations compared to oral risperidone. Long-acting paliperidone treatment gained incremental 0.903 QALYs on average compared to oral risperidone. The treatment of schizophrenia using long-acting paliperidone is associated with increased QALYs. It reduces incidence of adverse events, Results in better prevention of relapses and can be considered a cost-effective treatment in the Czech Republic.

Paliperidone extended release: a guide to its use in schizophrenia in adolescents aged ≥15 years

Oral paliperidone extended release (ER) [Invega®] has recently been approved for the treatment of schizophrenia in adolescents aged 15–17 years in the EU. The ER formulation of the drug provides consistent plasma drug concentrations, allowing convenient once-daily administration. In the subgroup of patients aged 15–17 years in clinical trials in adolescents aged 12–17 years with acute schizophrenia, paliperidone ER improved the symptoms and severity of schizophrenia, with improvements being maintained with longer-term treatment. Overall, paliperidone ER was generally well tolerated in adolescents, with a tolerability and safety profile similar to that in adults.

Lurasidone and Bipolar Disorder

Lurasidone and Bipolar Disorder

Changes in plasma concentrations of risperidone and 9-hydroxyrisperidone and the associated clinical effects during the switch from oral risperidone to extended-release paliperidone tablets in patients with schizophrenia

This study aimed to investigate changes in plasma concentrations of risperidone and 9-hydroxy-risperidone (9-OHR) and the associated clinical effects when switching from oral risperidone to extended-release (ER) paliperidone in patients with schizophrenia. This study included 25 patients with schizophrenia. Following a one-week screening period with a stable dose of risperidone, a six-week open-label switch study from risperidone to extended-release paliperidone (paliperidone ER) was conducted. Efficacy and safety assessments were performed on Day 1 and at Weeks 1, 2, 4, and 6. Plasma levels of the active fractions of oral risperidone and paliperidone ER were measured on Day 1 and at Week 1, respectively. Plasma levels of the active moiety (risperidone plus 9-OHR) while taking risperidone (mean dose: 4.0 mg) were significantly higher than plasma levels of 9-OHR while taking 6 mg of paliperidone ER. For 12 subjects taking only 3 mg of risperidone, plasma concentrations of the active moiety of risperidone were also significantly higher than those of 9-OHR while taking 6 mg of paliperidone ER. The amount of reduction in plasma levels was correlated with a temporal deterioration of clinical symptoms. These findings suggest that for patients with schizophrenia taking 3 mg or more of risperidone, an initial switching dose of 6 mg of paliperidone ER may be relatively low in terms of subsequent plasma concentrations and the associated clinical response.

Switching from oral risperidone to flexibly dosed oral paliperidone extended-release: core symptoms, satisfaction, and quality of life in patients with stable but symptomatic schizophrenia: the RISPALI study

Objective:The purpose of this prospective study was to evaluate the effects of switching from oral risperidone to flexibly dosed oral paliperidone extended-release (ER) in Brazilian adults with schizophrenia because of lack of efficacy, intolerability, or nonadherence after a minimum trial of 30 days on adequate (labeled) doses of oral risperidone, according to individual clinical judgment.Research design and methods:Subjects with Positive and Negative Syndrome Scale total scores above 78, and/or intolerable adverse effects, with risperidone received open-label paliperidone ER 3 to 12 mg daily for 26 (main phase) to 52 (extension phase) weeks.Clinical trial registration:Clinicaltrials.gov identifier: NCT01010776.Results:The intent-to-treat (efficacy) populations comprised 213 subjects in the main phase and 159 in the extension phase. Of 213 subjects with baseline and post-baseline efficacy data, 154 (72.3%) switched from risperidone to paliperidone ER because of a lack of efficacy and 59 (27.7%) because of tolerability issues, according to individual clinical judgment. Paliperidone ER significantly (p < 0.0500) improved a broad spectrum of efficacy endpoints from baseline, as early as the first post-baseline visit (Visit 2; 4 weeks) and persisting through 26 to 52 weeks. On most efficacy endpoints, function improved from baseline to the first post-baseline visit (week 4) and remained significantly improved compared to baseline at each visit for paliperidone ER treatment, at weeks 8, 13, 26, 39, 26, and 52; data are reported herein mainly for 26 and 52 weeks compared to baseline. Significant improvements from baseline were observed for the Positive and Negative Syndrome Scale total score and subscale scores (each p < 0.0001 at 26 and 52 weeks vs. baseline); and personal and social functioning (p < 0.0001 at 26 and 52 weeks). Paliperidone ER also significantly improved health-related quality of life (Short-Form 36) from baseline, particularly on the Mental Component Summary (p = 0.0011 at 26 weeks and p = 0.0019 at 52 weeks). Treatment with paliperidone ER also significantly improved (vs. baseline) sleep quality (according to decreases on the Pittsburgh Sleep Quality Index; p < 0.0001 at each visit vs. baseline) and disease severity (Clinical Global Impression–Severity; p < 0.0001 at each visit vs. baseline). Paliperidone ER was well tolerated. Adverse events occurring in at least 10% of subjects in either phase were insomnia (14.9% in the main phase and 8.8% in the extension phase); increased body weight (10.7% and 12.6%, respectively); and anxiety (10.7% and 2.5%). Most of these adverse events were: 1) rated as mild or moderate; 2) did not prompt interventions such as paliperidone ER dose adjustment or interruption; and 3) decreased in frequency from the main to the extension phase.Conclusions:Oral paliperidone ER is a rational treatment alternative for patients with schizophrenia whose antipsychotic regimens are switched because of unsuccessful treatment with oral risperidone according to individual clinical judgment. Study limitations included the open-label study design, lack of placebo, and use of subjective clinical judgment to determine lack of efficacy, intolerability, or nonadherence with oral risperidone.

Tardive Dyskinesia Induced by a Switch From Haloperidol Depot to Paliperidone Palmitate

Tardive Dyskinesia Induced by a Switch From Haloperidol Depot to Paliperidone Palmitate

Successful Use of Paliperidone in a Clozapine-Resistant Schizophrenic Patient

Back to table of contents Previous article Next article LettersFull AccessSuccessful Use of Paliperidone in a Clozapine-Resistant Schizophrenic PatientTing-Hung Hsieh, M.D., and Cheng-Tsung Liu, M.D.Ting-Hung HsiehSearch for more papers by this author, M.D., and Cheng-Tsung LiuSearch for more papers by this author, M.D.Published Online:1 Apr 2013https://doi.org/10.1176/appi.neuropsych.12040087AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The use of paliperidone has been examined in many studies since it was first utilized in schizophrenic patients. Here, we describe a patient with clozapine-resistant schizophrenia, whose psychosis and associated depression remitted significantly after switching treatment from clozapine to paliperidone.Case Report“Mr. Y,” who was a 35-year-old man with a 10-year history of schizophrenia, was hospitalized because of frequent auditory hallucinations, persecutory delusions, and associated depression. He had been treated with olanzapine 20 mg daily, quetiapine 800 mg daily, and clozapine 400 mg daily, for around 1–2 months each. Sertraline 100 mg daily had also been administered concurrently with each of these medications since hospitalization. However, psychotic symptoms and associated depression continued to worsen, even though behavioral and psychosocial interventions had been utilized, as well. Therefore, paliperidone was considered with the hopes of significantly improving his symptoms.In a 1-month period, clozapine had been gradually tapered off and then discontinued, while paliperidone had been titrated from 3 mg daily to 12 mg daily. Sertraline 100 mg daily had been used continuously. When paliperidone 9 mg daily was used, Mr. Y had fewer auditory hallucinations and feelings of being persecuted. He also felt less depressed, and could actively participate in rehabilitative activities. Adverse effects did not occur during the period of drug-switching, and his psychotic symptoms had not noticeably worsened in the 3 months since paliperidone was started.DiscussionClozapine has been considered probably the most effective atypical antipsychotic agent for patients with refractory schizophrenia. However, the risk of agranulocytosis, the requirement of periodic monitoring of blood neutrophil counts, and other side effects considerably decrease the drug compliance of patients. Consequently, clinicians may choose other antipsychotic agents instead of clozapine.In contrast, paliperidone has shown clinical efficacy, safety, and tolerability in the acute and maintenance treatment of schizophrenia.1,2 Even in elderly patients and those with liver dysfunction, paliperidone is generally well tolerated.3,4 Interestingly, depressed mood is likely to be improved when paliperidone is used, and there were case reports describing patients who displayed manic symptoms after paliperidone was administered, indicating that paliperidone may have the potential to alter mood states.5Although a single case does not firmly demonstrate that paliperidone is always effective in clozapine-resistant patients, we believe that paliperidone might be a useful medication for a certain group of schizophrenic patients who show poor response to other medications, especially when their symptoms are associated with depression. Therefore, clinicians are encouraged to use paliperidone when other antipsychotics, including clozapine, fail to improve the symptoms in schizophrenic patients.The limitation of this case report is that we could not determine whether the improvement in depression was due to paliperidone only, paliperidone combined with sertraline, or ameliorated psychotic symptoms followed by secondary improvement of depression. In summary, for schizophrenic patients associated with depression, further studies are required to investigate whether preferable outcomes will be obtained when paliperidone is used as a monotherapy or used with other psychotropics.Tri-Services General Hospital, Beitou Branche-mail: Dr. Liu: ablush.[email protected]hinet.netReferences1 Kramer M, Simpson G, Maciulis V, et al.: Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2007; 27:6–14Crossref, Medline, Google Scholar2 Meltzer HY, Bobo WV, Nuamah IF, et al.: Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week, placebo-controlled studies. J Clin Psychiatry 2008; 69:817–829Crossref, Medline, Google Scholar3 Tzimos A, Samokhvalov V, Kramer M, et al.: Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension. Am J Geriatr Psychiatry 2008; 16:31–43Crossref, Medline, Google Scholar4 Paulzen M, Orfanos S, Gründer G: Remission of drug-induced hepatitis after switching from risperidone to paliperidone. Am J Psychiatry 2010; 167:351–352Crossref, Medline, Google Scholar5 Hsieh C-HMD, Liou Y-JMD: Manic symptoms induced by paliperidone. J Clin Psychopharmacol 2010; 30:202–204Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byPaliperidone Palmitate for Refractory and Clozapine-Resistant SchizophreniaJoão Paulo Maia-de-Oliveira, M.D., M.Sc., Ph.D. Emerson Arcoverde Nunes, M.D. Juliana Mayumi Ushirohira, M.D. João Paulo Machado-de-Sousa, Ph.D. Rodrigo Affosenca Bressan, M.D., Ph.D. Jaime Eduardo Cecílio Hallak, M.D., Ph.D.26 February 2015 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 27, No. 1 Volume 25Issue 2 Spring 2013Pages E36-E36 Metrics PDF download History Published online 1 April 2013 Published in print 1 April 2013

Incidence and time course of extrapyramidal symptoms with oral and long-acting injectable paliperidone: a posthoc pooled analysis of seven randomized controlled studies

BackgroundThe purpose of this study was to compare incidence rates and time course of extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) between oral and long-acting injectable (LAI) paliperidone.MethodsThe analysis included pooled data (safety analysis set, 2,256 antipsychotic-treated and 865 placebo-treated patients with schizophrenia) from seven randomized, double-blind, placebo-controlled paliperidone studies (three oral [6 weeks each] and four LAI [9–13 weeks]) and assessed comparable doses (oral, 3–15 mg; LAI, 25–150 mg eq. [US doses 39–234 mg]). We summarized incidence rates and time of onset for EPS-related TEAE, categorized by EPS group terms, ie, tremor, dystonia, hyperkinesia, parkinsonism, and dyskinesia, and use of anti-EPS medication. Mean scores over time for the Abnormal Involuntary Movement Scale (AIMS, for dyskinesia), Barnes Akathisia Rating Scale (BARS, for akathisia), and Simpson Angus Rating Scale (SAS, for parkinsonism) were graphed.ResultsIncidence rates for all categories of spontaneously reported EPS-related TEAEs except for hyperkinesia, were numerically lower in pooled LAI studies than in pooled oral studies. Highest rates were observed in the first week of paliperidone-LAI (for all EPS symptoms except dyskinesia) and oral paliperidone treatment (except parkinsonism and tremor). Anti-EPS medication use was significantly lower in LAI (12%) versus oral studies (17%, P = 0.0035). Mean values for EPS scale scores were similar between LAI and oral treatment at endpoint, and no dose response was evident. Mean reductions (standard deviation) from baseline to endpoint in EPS scale scores were larger for LAI (AIMS, −0.10 [1.27]; BARS, −0.09 [1.06]; SAS, −0.04 [0.20]) versus oral studies (AIMS, −0.08 [1.32]; BARS, −0.03 [1.24]; SAS, 0.0 [0.23]). These changes favored LAI for BARS (P = 0.023) and SAS (P < 0.0001), but not for AIMS (P = 0.49), at endpoint for the studies.ConclusionIn this posthoc descriptive analysis, incidence rates of spontaneously reported EPS-related TEAEs were numerically lower following approximately 90 days of exposure with LAI and approximately 40 days with oral paliperidone at comparable doses.

Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies

BackgroundIncreasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available.MethodsThis post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity.ResultsApproximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46–4.35; p < 0.001]. Similarly, risk of relapse after withdrawal of paliperidone ER treatment (placebo group of the paliperidone ER study) was higher than after withdrawal of PP (paliperidone ER placebo/PP placebo HR, 2.25; 95% CI, 1.59–3.18; p < 0.001). Stabilised schizophrenic subjects treated with PP maintained functioning demonstrated by the same proportions of subjects with mild to no difficulties in functioning at DB baseline and end point [Personal and Social Performance (PSP) scale total score >70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar.ConclusionsThis analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.