paliperidone-palmitate and Bipolar-Disorder

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Haloperidol; Humans; Lithium; Male; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tamoxifen; Valproic Acid

Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries).. We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556.. Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference - 5.83, 95% CI - 10.79 to - 0.87, I. IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Male; Paliperidone Palmitate; Risperidone; Schizophrenia

Paliperidone is FDA-approved for schizophrenia aged 12-17. However, the pharmacologic portfolio, extrapolation from adult studies, and the long track record of the parent drug, risperidone in child/adolescent psychiatric (CAP) population might expand its therapeutic potential.. EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies of using paliperidone in child psychiatry up to date of February 2019.. Sound evidence base supports its use in early-onset schizophrenia, juvenile bipolar, and autism spectrum disorder. A modicum of evidence supports its use in Tourette syndrome and as adjuventia in attention-deficit/hyperactivity disorder (ADHD).. Paliperidone has some dynamic and kinetic superiority to the parent drug risperidone. Nonetheless, larger rigorous studies would define the real place of the atypical antipsychotic paliperidone in child and adolescent psychiatry. Until then, risperidone with its long track record in CAP population would remain a first option though.

Topics: Adolescent; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Autism Spectrum Disorder; Basal Ganglia Diseases; Bipolar Disorder; Child; Child Psychiatry; Humans; Long QT Syndrome; Off-Label Use; Paliperidone Palmitate; Schizophrenia; Tourette Syndrome; Treatment Outcome

This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states.. The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.. The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Thiazoles; Valproic Acid

Paliperidone may be effective for the treatment of bipolar disorder (BD); however, the evidence has been mixed. This is the first meta-analysis to evaluate the efficacy, safety, and tolerability of paliperidone for the treatment of BD. We performed a systematic search of the literature using major electronic databases from inception to January 27, 2017. Randomized control trials (RCTs) investigating paliperidone treatment among patients with BD versus a placebo or other second-generation antipsychotics were included. We then performed exploratory random-effects meta-analysis. The 3 included RCTs compared paliperidone with placebo (667 patients received paliperidone and 369 received a placebo). The dose of paliperidone in the included studies ranged from 3 to 12 mg/day. Paliperidone did not significantly improve manic symptoms (Hedges' g = -0.221, p = .067, k = 5) compared with a placebo; however, it was superior to a placebo in improving psychosocial function (Hedges' g = -0.156, p = .042, k = 3) and general severity (Hedges' g = -0.205, p = .001, k = 5). Paliperidone was associated with a greater use of anticholinergic medications (p = .002), increased body weight (p < .001), and higher serum prolactin level (p < .001) compared with a placebo. Our preliminary results suggest that paliperidone does not offer significant benefits for the treatment of mania symptoms in BD compared with a placebo. In addition, treatment with paliperidone was associated with a higher incidence of adverse effects. Because of the limited number of studies, further well-designed RCTs are warranted. (PsycINFO Database Record

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Paliperidone Palmitate; Randomized Controlled Trials as Topic; Weight Gain; Young Adult

Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains.. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline.. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies.. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies.. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depression; Double-Blind Method; Female; Humans; Male; Middle Aged; Paliperidone Palmitate; Prospective Studies; Psychotic Disorders; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

Schizoaffective disorder (SCA) is a complex mental illness characterized by psychosis and affective symptoms. Treatment usually involves concomitant therapy with antipsychotics, mood stabilizers, and/or antidepressants. Effective treatment must address acute symptoms, maintain long-term stability, promote recovery, and improve patient functioning.. Data from 3 pivotal studies evaluating the acute and maintenance treatment of SCA with paliperidone are reviewed. Two formulations of paliperidone have been studied for these indications: an extended-release oral formulation (NCT00397033, NCT00412373) and long-acting injectable once-monthly paliperidone palmitate (NCT01193153). The reported effects of these formulations on psychotic, depressive, and manic symptoms are discussed.. Both formulations were found to be safe and effective for the acute and maintenance treatment of SCA. Of critical importance for this treatment population is that rapid improvement was seen in all major symptoms of SCA, including psychosis, depression, and mania. Mediation analyses suggest that the known antipsychotic effects of paliperidone occur independently of its antidepressant effects. Both formulations of the drug are effective when used as monotherapy or adjunctively with antidepressants or mood stabilizers. Beyond symptom control, both formulations improved patient functioning and increased patient satisfaction.

Topics: Administration, Oral; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Delayed-Action Preparations; Depression; Humans; Injections, Intramuscular; Paliperidone Palmitate; Psychotic Disorders; Treatment Outcome

This analysis explored the relationship between ratings on HAM-D-17 or YMRS and those on the depressive or manic subscale of CGI-S for schizoaffective disorder (CGI-S-SCA).. This post hoc analysis used the database (N=614) from two 6-week, randomized, placebo-controlled studies of paliperidone ER versus placebo in symptomatic subjects with schizoaffective disorder assessed using HAM-D-17, YMRS, and CGI-S-SCA scales. Parametric and nonparametric regression models explored the relationships between ratings on YMRS and HAM-D-17 and on depressive and manic domains of the CGI-S-SCA from baseline to the 6-week end point. A clinically meaningful improvement was defined as a change of 1 point in the CGI-S-SCA score. No adjustment was made for multiplicity.. Multiple linear regression models suggested that a 1-point change in the depressive domain of CGI-S-SCA corresponded to an average 3.6-point (SE=0.2) change in HAM-D-17 score. Similarly, a 1-point change in the manic domain of CGI-S-SCA corresponded to an average 5.8-point (SE=0.2) change in YMRS score. Results were confirmed using local and cumulative logistic regression models in addition to equipercentile linking.. Lack of subjects scoring over the complete range of possible scores may limit broad application of the analyses.. Clinically meaningful score changes in depressive and manic domains of CGI-S-SCA corresponded to approximately 4- and 6-point score changes on HAM-D-17 and YMRS, respectively, in symptomatic subjects with schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depression; Female; Humans; Isoxazoles; Male; Paliperidone Palmitate; Psychiatric Status Rating Scales; Psychotic Disorders; Pyrimidines; Severity of Illness Index

The introduction of second-generation antipsychotics (SGAs) over the past 2 decades generated considerable optimism that better antipsychotic treatments for schizophrenia and bipolar disorder were possible. SGAs offer several tolerability benefits over first-generation antipsychotics (FGAs), particularly with respect to extrapyramidal symptoms. However, SGAs can induce serious metabolic dysregulations, especially in drug-naive, first-episode, and child and adolescent populations, with olanzapine and clozapine having the highest propensity to cause these abnormalities. In this context, newer SGAs were developed to further improve the adverse effect burden of available agents. However, until now, the metabolic risk profile of the newly approved SGAs - asenapine, iloperidone, lurasidone and paliperidone (paliperidone extended release and paliperidone palmitate) - has not been compared.. The objective of this systematic review and exploratory meta-analysis was to assess the effects of asenapine, iloperidone, lurasidone and paliperidone on body weight and other metabolic parameters (cholesterol, triglycerides and glucose), as this information is relevant to guide clinical decision making.. A systematic literature search (1966-March 2012), using the Cochrane Central Register of Controlled Trials and MEDLINE, CINAHL and EMBASE databases, was conducted for randomized, placebo-controlled and head-to-head clinical trials of asenapine, iloperidone, lurasidone and paliperidone. Published and unpublished data on changes in body weight and glucose and lipid metabolism parameters were extracted. For placebo-controlled, short-term (≤12 weeks) and longer-term (>12 weeks) trials with available data on ≥7% weight increase compared with pre-treatment weight, or mean weight change with standard deviation, a formal meta-analysis was performed, estimating the pooled effect size (represented as relative risk [RR], numbers-needed-to-harm [NNH] and weighted mean difference [WMD]). An exploratory meta-analysis was also performed for the other metabolic variables (cholesterol, triglycerides and glucose). Data from active- and placebo-controlled studies were used for a pooled comparison of simple mean changes in weight, cholesterol, triglyceride and glucose levels.. Fifty-six trials (n = 21 691) in schizophrenia (N = 49, n = 19 299) or bipolar disorder (N = 7, n = 2392) were identified (asenapine: N = 9, iloperidone: N = 11, lurasidone: N = 8, paliperidone: N = 28). Most of the trials (64.3%) were of ≤12 weeks' duration. In the short-term trials, compared with placebo, a ≥7% weight increase was statistically significantly (p < 0.05) most prevalent for asenapine (5 trials, n = 1360, RR = 4.09, 95% confidence interval [CI] 2.25, 7.43, NNH = 17), followed by iloperidone (4 trials, n = 1931, RR = 3.13, 95% CI 2.08, 4.70, NNH = 11) and paliperidone (12 trials, n = 4087, RR = 2.17, 95% CI 1.64, 2.86, NNH = 20). The effect of lurasidone on body weight (6 trials, n = 1793, RR = 1.42, 95% CI 0.87, 2.29) was not statistically significant. Short-term weight gain was statistically significantly (p < 0.001) greater than placebo with iloperidone (1 trial, n = 300, +2.50 kg, 95% CI 1.92, 3.08), paliperidone (15 trials, n = 3552, +1.24 kg, 95% CI 0.91, 1.57), asenapine (3 trials, n = 751, +1.16 kg, 95% CI 0.83, 1.49), as well as with lurasidone (5 trials, n = 999, +0.49 kg, 95% CI 0.17, 0.81, p < 0.01). Sufficient meta-analysable, longer-term, weight change data were only available for asenapine and paliperidone, showing statistically significantly (p < 0.001) greater weight gain versus placebo for both drugs (asenapine, 3 trials, n = 311, +1.30 kg, 95% CI 0.62, 1.98; paliperidone, 6 trials, n = 1174, +0.50 kg, 95% CI 0.22, 0.78). Although statistically significant, in general, no clinically meaningful differences were observed between the four newly approved SGAs and placebo regarding the mean change from baseline to endpoint in cholesterol levels in short-term trials, with the exception of iloperidone for total cholesterol (1 trial, n = 300, +11.60 mg/dL, 95% CI 4.98, 18.22, p ≤ 0.001), high-density cholesterol (1 trial, n = 300, +3.6 mg/dL, 95% CI 1.58, 5.62, p < 0.001) and low-density cholesterol (1 trial, n = 300, +10.30 mg/dL, 95% CI 4.94, 15.66, p < 0.001) and with the exception of lurasidone for high-density cholesterol (5 trials, n = 1004, +1.50 mg/dL, 95% CI 0.56, 2.44, p < 0.01). Asenapine increased total cholesterol statistically significantly (p < 0.05) during longer-term treatment (1 trial, n = 194, +6.53 mg/dL, 95% CI 1.17, 11.89). Regarding triglycerides, only short-term (3 trials, n = 1152, +1.78 mg/dL, 95% CI 0.40, 3.17, p < 0.01) and longer-term treatment with paliperidone (4 trials, n = 791, -0.20 mg/dL, 95% CI -. While preliminary data suggest the lowest weight gain potential with lurasidone and potentially relevant short-term metabolic effects for asenapine and iloperidone, data are still too sparse to comprehensively evaluate the metabolic safety of the newly approved SGAs. Therefore, there is a clear need for further controlled studies to evaluate whether these agents are less problematic regarding treatment-emergent weight gain and metabolic disturbances than other currently available antipsychotics.

Topics: Antipsychotic Agents; Bipolar Disorder; Blood Glucose; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Isoindoles; Isoxazoles; Lipid Metabolism; Lurasidone Hydrochloride; Paliperidone Palmitate; Piperidines; Pyrimidines; Randomized Controlled Trials as Topic; Schizophrenia; Thiazoles; Weight Gain

Paliperidone (9-hydroxy-risperidone), the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER), and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug-drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially higher costs as compared with risperidone. However, in terms of pharmacology, the available evidence cautiously suggests a place for PER in modern antipsychotic therapy.

Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Delayed-Action Preparations; Humans; Isoxazoles; Paliperidone Palmitate; Pyrimidines; Schizophrenia

Paliperidone extended-release (ER), a once-daily, oral, atypical antipsychotic, has been available in the USA and the EU for the treatment of schizophrenia for more than 2 years and was recently (July 2009) approved in the USA for treatment of schizoaffective disorder. Additional data on its efficacy and safety, including that for additional indications, is emerging.. This review provides a background on the compound and summarizes recent data available on treatment of schizophrenia, including comparative data with other antipsychotics, and efficacy and safety data from clinical trials in schizoaffective and bipolar disorders.. The reader will gain knowledge of the compound and the existing clinical data so far for paliperidone ER.. Paliperidone ER is effective for the treatment of schizophrenia and is at present the only antipsychotic approved in the USA for treatment of schizoaffective disorder. Its efficacy and tolerability profile in treating patients with schizophrenia or schizoaffective disorder indicates that paliperidone ER offers an important treatment option among atypical antipsychotic therapy for these patients.

Topics: Animals; Bipolar Disorder; Delayed-Action Preparations; Humans; Isoxazoles; Paliperidone Palmitate; Psychotic Disorders; Pyrimidines; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To evaluate the cost-effectiveness of aripiprazole once-monthly 400/300 mg (AOM 400) in maintenance monotherapy treatment of bipolar I disorder (BP-I).. A de novo lifetime Markov model was developed for BP-I using available data for AOM 400 and relevant comparators. Base-case analysis considered costs and outcomes from the US payer perspective.. The cost per quality-adjusted life year gained with AOM 400 versus comparators ranged from US$2007 versus oral asenapine to dominance (i.e., lower cost with quality-adjusted life gain) versus long-acting injectable risperidone, paliperidone palmitate, oral cariprazine and best supportive care. Patients treated with AOM 400 were estimated to have fewer mood episodes and hospitalizations per patient (5.37) than comparators (6.33, asenapine or cariprazine; 6.54, risperidone long-acting injectable; 7.64, paliperidone palmitate; and 8.93, best supportive care). Sensitivity analyses showed results were robust to parameter uncertainty.. AOM 400 may be considered cost effective in the maintenance monotherapy treatment of BP-I in adults.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Administration Schedule; Drug Costs; Female; Humans; Injections, Intramuscular; Male; Markov Chains; Middle Aged; Paliperidone Palmitate; Piperazines; Quality-Adjusted Life Years; Risperidone; Schizophrenia; Young Adult

Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented.. The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse.. 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49 times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001, Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and 15.2% for paliperidone monthly. For monotherapy, relapse risk was 3.38 times greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times greater with placebo (P = .021). Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale (P = .014, mixed-model repeated-measures analysis). The most common adverse events (placebo, paliperidone monthly) were increased weight (4.7%, 8.5%), insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly.. Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder.. ClinicalTrials.gov identifier: NCT01193153.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Palmitates; Placebos; Pregnancy; Psychotic Disorders; Recurrence; Secondary Prevention; Treatment Outcome; Young Adult

This analysis explored the relationship between ratings on HAM-D-17 or YMRS and those on the depressive or manic subscale of CGI-S for schizoaffective disorder (CGI-S-SCA).. This post hoc analysis used the database (N=614) from two 6-week, randomized, placebo-controlled studies of paliperidone ER versus placebo in symptomatic subjects with schizoaffective disorder assessed using HAM-D-17, YMRS, and CGI-S-SCA scales. Parametric and nonparametric regression models explored the relationships between ratings on YMRS and HAM-D-17 and on depressive and manic domains of the CGI-S-SCA from baseline to the 6-week end point. A clinically meaningful improvement was defined as a change of 1 point in the CGI-S-SCA score. No adjustment was made for multiplicity.. Multiple linear regression models suggested that a 1-point change in the depressive domain of CGI-S-SCA corresponded to an average 3.6-point (SE=0.2) change in HAM-D-17 score. Similarly, a 1-point change in the manic domain of CGI-S-SCA corresponded to an average 5.8-point (SE=0.2) change in YMRS score. Results were confirmed using local and cumulative logistic regression models in addition to equipercentile linking.. Lack of subjects scoring over the complete range of possible scores may limit broad application of the analyses.. Clinically meaningful score changes in depressive and manic domains of CGI-S-SCA corresponded to approximately 4- and 6-point score changes on HAM-D-17 and YMRS, respectively, in symptomatic subjects with schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depression; Female; Humans; Isoxazoles; Male; Paliperidone Palmitate; Psychiatric Status Rating Scales; Psychotic Disorders; Pyrimidines; Severity of Illness Index

Treatment studies for the management of pediatric bipolar disorder are limited.. This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders.. An 8-week, prospective, open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders (depression, psychosis, attention-deficit/hyperactivity disorder [ADHD]). Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impression scale (CGI), Children's Depression Rating Scale-Revised (CDRS-R), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis.. Fifteen youth with bipolar spectrum disorders (YMRS at entry: 32.8 ± 6.1) were enrolled in the study and 11 (73 %) completed the 8-week trial. The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects. Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores (-18.7 ± 13.9, p < 0.001) at endpoint. Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms. Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight (4.1 ± 5.5 lb) were substantial.. Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth. Future placebo-controlled studies are warranted to confirm these findings.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Female; Humans; Isoxazoles; Male; Paliperidone Palmitate; Pilot Projects; Prospective Studies; Psychiatric Status Rating Scales; Pyrimidines; Surveys and Questionnaires; Treatment Outcome

Atypical antipsychotics are effective in the treatment of bipolar I disorder. In this 3-week double-blind study, the efficacy and safety of paliperidone extended-release (ER) tablets were assessed in patients with acute mania.. Patients experiencing a manic or mixed episode (Young Mania Rating Scale [YMRS] total score ≥20), were randomly assigned to 1 of 3 fixed doses of once-daily paliperidone ER (3, 6, or 12-mg), or placebo (1:1:1:1 ratio).. In total, 469 patients were randomly assigned to treatment with paliperidone ER 3mg (n=112), 6 mg (n=120), or 12 mg (n=115); or placebo (n=122). Mean (SD) change in YMRS total score from baseline to the 3-week endpoint (primary variable) was statistically significantly different for the paliperidone ER 12 mg group (-13.5 [9.17], p=0.025), but not the 6 mg (-11.4 [9.98], p=0.57) or 3mg (-9.1 [11.18], p=0.79) groups compared with placebo (-10.1 [10.21]). Headache was the most common treatment-emergent adverse event (17% total paliperidone ER versus 12% placebo).. A statistically significant (p=0.0032) treatment-by-country interaction occurred, which confounded interpretation of study results. Paliperidone ER and placebo did not differ statistically for the primary efficacy variable among patients from the United States sites (74% of the intent-to-treat analysis set).. Paliperidone ER 12 mg/day was superior to placebo in the treatment of acute mania. Change from baseline in YMRS total score increased with the dose of paliperidone ER. Paliperidone ER was generally tolerated by patients with bipolar I disorder and no new safety signal was detected.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Treatment Outcome; Young Adult

Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder. We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder.. Patients (n=766), aged 18 to 65 years inclusive, with current manic or mixed episodes were initially randomized (4:1) to flexibly-dosed paliperidone ER (3-12 mg/day) or olanzapine (5-20 mg/day; 3-week acute treatment phase); responders continued the same treatment (12-week continuation phase). Patients on paliperidone ER who achieved remission during this phase were randomized (1:1) to fixed-dose paliperidone ER (n=152) or placebo (n=148); those on olanzapine continued to receive that at fixed dose (n=83) (maintenance phase).. Median time to recurrence of any mood symptoms (primary endpoint) was: 558 days (paliperidone ER), 283 days (placebo) and not observed with olanzapine (<50% of patients experienced recurrence). Time to recurrence of any mood symptoms was significantly longer with paliperidone ER than placebo (p=0.017; based on weighted Z-test at 0.0198 significance level; hazard ratio [placebo: paliperidone ER; unweighted 95% confidence interval]: 1.43 [1.03; 1.98]); the difference was significant for preventing recurrence of manic, but not depressive, symptoms. Treatment-emergent adverse events (maintenance phase) occurred more often in olanzapine group (64%) than placebo (59%) or paliperidone ER groups (55%).. Responder-enriched design prevents extrapolation of data to patients not previously stabilized on paliperidone ER.. Paliperidone ER significantly delayed the time to recurrence of any mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety concerns emerged.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Pyrimidines; Secondary Prevention; Young Adult

Combination treatment with atypical antipsychotics and a mood stabilizer is often recommended for treatment of manic or mixed episodes associated with bipolar I disorder.. Eligible patients (n=300) with a Young Mania Rating Scale (YMRS) total score ≥20 were randomly allocated (1:1) to continue mood stabilizer monotherapy or receive flexibly-dosed paliperidone ER (3-12 mg/day) in addition (combination treatment) for 6 weeks. The primary efficacy variable was the change from baseline to endpoint in the YMRS total score.. The mean (SD) YMRS total score at baseline was 26.7 (5.26); 33% of patients presented with a mixed (as distinct from a manic) episode and 62% were on valproate and 38% on lithium. The mean (SD) change from baseline to endpoint in the YMRS total score was not significantly different for combination treatment (-14.3 [10.0]) compared with mood stabilizer monotherapy (-13.2 [10.9]; p=0.16). Combination treatment also failed to separate from mood stabilizer monotherapy for the secondary efficacy measures. The incidence of treatment-emergent adverse events was higher with combination treatment (70%) than with mood stabilizer monotherapy (54%); insomnia was the most common adverse event in both treatment groups (11%).. The relatively low doses of paliperidone ER used in this study and the conduct across different countries may have contributed to its failure to differentiate combination treatment from mood stabilizer monotherapy for the primary and secondary efficacy measures.. In this study, flexibly-dosed paliperidone ER used as adjunctive therapy to mood stabilizers did not demonstrate efficacy over mood stabilizer monotherapy. No new safety signals were observed with combination treatment in this population.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Isoxazoles; Lithium Compounds; Male; Paliperidone Palmitate; Psychiatric Status Rating Scales; Pyrimidines; Treatment Outcome; Valproic Acid

To evaluate the antimanic efficacy and safety of paliperidone extended-release (ER) tablets in patients with bipolar I disorder.. This study included a 3-week, double-blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score >or= 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3-12 mg/day), quetiapine (400-800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy.. Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: -5.5 (-7.57; -3.35); p < 0.001} and noninferior to quetiapine at the 12-week endpoint [least-squares mean difference (95% CI): 1.7 (-0.47; 3.96)]. The median mode dose during the 12-week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine. The most common (>or= 10%) treatment-emergent adverse events during the 12-week period were: headache (16%), somnolence (10%), and akathisia (10%) for paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase >or= 7% from baseline to 12-week endpoint was 8% with paliperidone ER and 17% with quetiapine. A higher percentage of paliperidone ER (13.9%) versus quetiapine patients (7.5%) 'switched to depression' at the12-week endpoint.. Paliperidone ER (3-12 mg/day) was efficacious and tolerable in the treatment of acute mania.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Psychiatric Status Rating Scales; Pyrimidines; Quetiapine Fumarate; Treatment Outcome

A population model was developed with the aim to simultaneously describe risperidone and 9-hydroxyrisperidone pharmacokinetics; to obtain estimates for pharmacokinetic parameters and associated inter- and intra-individual variability of risperidone and 9-hydroxyrisperidone; and to evaluate the influence of patient demographic characteristics and other factors on risperidone, 9-hydroxyrisperidone, and active moiety pharmacokinetics. Data were obtained from 407 patients enrolled in four Phase 1 (serial blood sampling) and three Phase 3 trials (sparse sampling), representing dosage regimens ranging from 4 mg single dose to flexible 1-6 mg once daily. A pharmacokinetic model with two-compartment submodels for risperidone and 9-hydroxyrisperidone disposition and a sequential zero- and first-order absorption pathway was selected based on prior knowledge. A mixture model was incorporated due to CYP2D6 polymorphism of risperidone conversion to 9-hydroxyrisperidone. Patient characteristics tested as potential covariates were: age, sex, race, body weight, lean body mass, body mass index, creatinine clearance, liver function laboratory parameters, study, and carbamazepine comedication. The quasi-clearance of active moiety (the sum of risperidone and 9-hydroxyrisperidone) was simulated and linear regression performed to identify significant covariates. The selected pharmacokinetic model described the plasma concentration-time profiles for risperidone and 9-hydroxyrisperidone quite well and was able to determine each patient's phenotype. Covariates significantly affecting the pharmacokinetics were carbamazepine comedication, and study because the proportion of patients assigned to the intermediate metabolizer status decreased from single to multiple dosing while the proportion assigned to extensive metabolizer status increased. Covariates with limited and clinically irrelevant effects on active moiety concentrations were patient phenotype, race, and total protein. Carbamazepine also decreased active moiety concentrations.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Computer Simulation; Cytochrome P-450 CYP2D6; Databases as Topic; Drug Administration Schedule; Female; Humans; Isoxazoles; Linear Models; Male; Middle Aged; Models, Biological; Paliperidone Palmitate; Phenotype; Population Surveillance; Pyrimidines; Reproducibility of Results; Risperidone; Tablets

Topics: Antipsychotic Agents; Bipolar Disorder; Drug Administration Schedule; Drug Monitoring; Female; Humans; Male; Paliperidone Palmitate; Psychotic Disorders; Schizophrenia; Treatment Outcome

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.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Delayed-Action Preparations; Depression; Female; Humans; Injections; Male; Mania; Middle Aged; Paliperidone Palmitate; Prospective Studies; Psychiatric Status Rating Scales; Treatment Outcome; Young Adult

Literature assessing the use of long-acting injectable paliperidone palmitate in patients with bipolar I disorder is limited. The aim of this retrospective study was to determine the effectiveness of long-acting injectable paliperidone palmitate treatment on relapse and hospitalization in a real-world setting. Patients with bipolar I disorder aged 18-65 years, who were treated with paliperidone palmitate once-monthly (PP1M) for at least one year, were included. The rate of relapse, hospitalization, and length of hospital stay were collected. Safety outcomes included levels of prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein. The data of 36 patients who met the study criteria were evaluated. Number and length of hospitalizations, number of manic and mixed episodes significantly decreased after PP1M addition. When we compared the prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein levels as an indicator of the safety of treatment, there was no statistically significant change in these values before and after PP1M addition. Our findings suggested PP1M may be effective in reducing manic and mixed episodes. Limitations include a mirror image retrospective design and small sample size.

Topics: Antipsychotic Agents; Bipolar Disorder; Hospitalization; Humans; Paliperidone Palmitate; Recurrence; Retrospective Studies; Schizophrenia

Outpatient facilities, such as community behavioral health organizations (CBHOs), play a critical role in the care of patients with serious mental illness, but there is a paucity of "real-world" patient outcomes data from this health care setting. Therefore, we conducted The Research and Evaluation of Antipsychotic Treatment in Community Behavioral Health Organizations, Outcomes (REACH-OUT) trial, a real-world, prospective, noninterventional observational study of patients with mental illness treated at CBHOs across the United States. We describe demographic and clinical characteristics, antipsychotic therapy (APT) treatment patterns, and health care resource utilization in patients with schizophrenia undergoing medical care as usual.. This study enrolled adults with schizophrenia or bipolar I disorder who initiated APT treatment at various time points: 1) within 8 weeks of initiating risperidone long-acting injectables (RLAIs) or other APTs except paliperidone palmitate (PP), 2) after more than 24 weeks of continuous RLAI treatment, or 3) at any time after initiating PP LAI treatment (schizophrenia only). Study assessments were performed via participant interview, medical chart abstraction, and clinical survey at enrollment and at month 12.. A total of 1065 patients from 46 CBHOs were enrolled. Of these, 944 (88.6%) had a diagnosis of schizophrenia and 121 (11.4%) had bipolar I disorder. At enrollment, 599 (63.5%) of patients with schizophrenia were receiving RLAIs or PP LAI, 281 (29.8%) were receiving oral APTs, and 64 (6.8%) were receiving other injectable APTs. A number of differences in patient characteristics and outcomes were observed between patients in the LAI APT cohort and the oral APT cohort.. Descriptive analyses from this observational study suggest differences in the patient characteristics, treatment patterns, and clinical and economic outcomes among those with schizophrenia treated at CBHOs with LAI APT or oral APTs. Additional analyses will be conducted to delineate the impact of LAI APT versus oral APTs on patient outcomes.. Clinical Trial Registry: NCT01181960 . Registered 12 August 2010.

Topics: Administration, Oral; Adult; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Community Mental Health Services; Delayed-Action Preparations; Female; Follow-Up Studies; Humans; Injections; Male; Middle Aged; Paliperidone Palmitate; Practice Patterns, Physicians'; Prospective Studies; Risperidone; Schizophrenia; United States

To estimate the budget impact (BI) of introducing aripiprazole once-monthly 400 mg/300 mg (AOM 400) in the maintenance monotherapy treatment of bipolar I disorder versus long-acting injectables, oral antipsychotics and best supportive care.. A BI model was developed from a US-payer perspective using treatment-related, hospitalization and adverse event management cost estimates for a hypothetical 1,000,000-member health plan over a 5-year period.. Market share of AOM 400 was predicted to increase from 0.6% in Year 1 (current scenario) to 1.3% in Year 5 (predicted scenario), with predicted increases for paliperidone palmitate, asenapine and cariprazine. Treatment-related costs explained the BI increase, while adverse event and hospitalization costs were reduced. The per member per month incremental cost ranged from US$0.06 to US$0.26 in Years 1-5. The largest increases were predicted for paliperidone palmitate.. As market shares of atypical antipsychotics are predicted to increase, payers may wish to re-evaluate their use.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Budgets; Cost-Benefit Analysis; Delayed-Action Preparations; Dibenzocycloheptenes; Drug Administration Schedule; Drug Costs; Health Care Costs; Heterocyclic Compounds, 4 or More Rings; Hospitalization; Humans; Injections, Intramuscular; Injections, Subcutaneous; Medication Adherence; Paliperidone Palmitate; Piperazines; Schizophrenia

To compare risk of hospitalization in patients with bipolar I disorder (BD-I) initiating long-acting injectable antipsychotics (LAIs).. Using Truven Health Analytics MarketScan. The adjusted odds of having hospitalization were significantly higher in haloperidol-LAI (Odds ratio [95% CI]: 1.39 [1.03-1.87] all-cause; p = 0.029; 1.41 [1.03-1.93] psychiatric-specific; p = 0.032) and risperidone-LAI (1.54 [1.12-2.13]; p = 0.009; 1.68 [1.20-2.37]; p = 0.003) users versus AOM 400 users. Risks of hospitalization did not differ comparing fluphenazine-LAI and paliperidone-LAI users with AOM 400 users.. AOM 400 may be more beneficial at reducing hospitalization rates in BD-I versus haloperidol-LAI and risperidone-LAI.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Databases, Factual; Delayed-Action Preparations; Female; Hospitalization; Humans; Injections; Male; Medicaid; Middle Aged; Paliperidone Palmitate; Risperidone; Schizophrenia; United States; Young Adult

The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions. The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions.. A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxy-RIS (9-OH-RIS) of 1,584 adult patients was analyzed. Four groups (n = 1,072) were compared: a control group without a potentially cytochrome interacting comedication (R0, n = 852), a group comedicated with valproate (VPA) (RVPA, n = 153), a group comedicated with lamotrigine (LMT) (RLMT, n = 46), and a group under concomitant medication with carbamazepine (CBZ) (RCBZ, n = 21). Dose-adjusted plasma concentrations (C/D ratio) for RIS, 9-OH-RIS and active moiety (AM) (RIS + 9-OH-RIS), as well as metabolic ratios (RIS/9-OH-RIS) were computed.. Groups did not differ with regard to the daily dosage (P = 0.46). Differences were detected for the distributions of the C/D ratios for RIS, 9-OH-RIS and AM (P = 0.003, P < 0.001 and P < 0.001, respectively). Differences remained significant after conducting a Bonferroni correction (P = 0.0125). Pairwise comparisons of the concomitant medication groups with the control group revealed significant differences; RIS C/D ratios were significantly higher in the VPA and the LMT group than in the control group (P = 0.013; P = 0.021). However, these differences did not remain significant after Bonferroni correction. In contrast, CBZ-treated patients showed lower dose-adjusted plasma concentrations of 9-OH-RIS (P < 0.001) as well as the AM (P < 0.001) than the control group; this difference survived the Bonferroni correction.. The data give evidence for pharmacokinetic interactions between RIS and different anticonvulsant mood stabilizers. Carbamazepine decreased serum concentrations of 9-OH-RIS and the AM when compared with the control group. In case of VPA and LMT, findings were less significant; hints for a weak RIS metabolism inhibition by LMT of unclear clinical significance were found.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lamotrigine; Male; Middle Aged; Paliperidone Palmitate; Risperidone; Triazines; Valproic Acid; Young Adult

Topics: Adolescent; Aripiprazole; Bipolar Disorder; Child; Child Psychiatry; Child Rearing; Cognitive Behavioral Therapy; Humans; Paliperidone Palmitate; Periodicals as Topic; Pragmatic Clinical Trials as Topic; Schizophrenia

Catatonia is a neuropsychiatric syndrome involving motor signs in association with disorders of mood, behavior, or thought. Bitemporal electrode placement electroconvulsive therapy (ECT) is a proven effective treatment for catatonia, and this mode of ECT delivery is the preferred method of treatment in this condition. Studies in major depressive disorder have demonstrated that suprathreshold, nondominant (right) hemisphere, unilateral electrode placement ECT has fewer adverse effects, especially cognitive adverse effects, than bitemporal ECT. This case series describes the use of right unilateral (RUL) ECT in 5 patients with catatonia. Before ECT, all 5 patients in this series initially failed therapy with benzodiazepines and psychotropic medications. Each catatonic patient received a series of 8 to 12 RUL ECT in an every-other-day series. After ECT, 4 of the 5 patients had a full recovery from catatonia. One patient achieved only partial response to RUL ECT, and no additional benefit was obtained with bitemporal ECT. All patients in this case series tolerated RUL ECT without major adverse effects. This case series illustrates successful use of RUL ECT in patients with catatonia and adds to the early literature demonstrating its effective use in treating this complex condition.

Topics: Adolescent; Adult; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Catatonia; Depressive Disorder, Major; Electroconvulsive Therapy; Female; GABA Modulators; Humans; Isoxazoles; Lorazepam; Lupus Erythematosus, Systemic; Male; Paliperidone Palmitate; Psychotic Disorders; Pyrimidines; Schizophrenia, Catatonic; Seizures; Treatment Outcome; Young Adult

Paliperidone palmitate (PP) is a recently introduced long-acting atypical, or second-generation, antipsychotic. Published data on PP are currently limited to controlled trials and case reports. In this observational study, we followed up 200 consecutive patients prescribed PP in normal practice. After 1 year, 65% of patients were still receiving PP. The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year, 3 years before initiation (P=0.0001). The mean number of bed days fell from 38.78 to 23.09/patient/year over the corresponding period (P=0.0001). The median number of bed days 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0. Outcomes were numerically but not statistically better in those continuing PP than in those who ceased PP within a year of initiation. PP was effective and well-tolerated and, given its positive effect on hospital bed days, broadly cost-effective.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Cohort Studies; Delayed-Action Preparations; Drug Monitoring; Electronic Health Records; Female; Follow-Up Studies; Hospitals, Urban; Humans; Isoxazoles; Length of Stay; London; Male; Middle Aged; Paliperidone Palmitate; Palmitates; Patient Acceptance of Health Care; Patient Compliance; Psychotic Disorders; Recurrence; Schizophrenia; Young Adult

Given the potential concomitant use of carbamazepine and paliperidone extended-release (ER) in the treatment of schizophrenia or schizoaffective disorder, this open-label, two-treatment sequential study investigated the effect of repeated administration of carbamazepine on the steady-state pharmacokinetics of paliperidone. Sixty-four patients with a diagnosis of schizophrenia or bipolar-I disorder received the following treatments in a fixed sequential order, without washout between treatments: (i) paliperidone ER 6 mg tablet once daily for 7 days, and (ii) paliperidone ER 6 mg once daily concomitantly with carbamazepine 200 mg twice daily for the subsequent 21 days. Upon coadministration with carbamazepine, paliperidone steady-state total exposure (AUC24 h ) and peak plasma concentrations (Cmax ) decreased by approximately 37% [LSM ratio-AUC24 h : 63.4 (90% CI: 57.19; 70.29); Cmax : 62.47 (90% CI: 55.77; 69.98)]. This decrease is accounted for to a substantial degree by a 35% increase in renal clearance of paliperidone, likely as a result of induction of renal P-glycoprotein by carbamazepine. A 14% decrease in the amount of drug excreted unchanged in the urine suggests that carbamazepine coadministration has a limited effect on the intestinal absorption or cytochrome metabolism of paliperidone.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B; Bipolar Disorder; Bulgaria; Carbamazepine; Croatia; Delayed-Action Preparations; Drug Administration Schedule; Drug Compounding; Drug Interactions; Female; Humans; Intestinal Absorption; Male; Metabolic Clearance Rate; Middle Aged; Paliperidone Palmitate; Renal Elimination; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Humans; Injections, Intramuscular; Isoxazoles; Male; Paliperidone Palmitate; Palmitates

To examine (1) arrest outcomes for adults with schizophrenia and bipolar disorder who were treated with first-generation antipsychotics (FGAs) or second-generation atypical antipsychotics (SGAs) and (2) the interaction between medication class and outpatient services in a Florida Medicaid program.. In a secondary data analysis, Florida Medicaid data covering the period from July 1, 2002, to March 31, 2008, were used to identify persons diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder and to examine antipsychotic medication episodes lasting at least 60 days. There were 93,999 medication episodes in the population examined (N = 36,519). Medication episodes were coded as (1) SGA-aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting therapy, or ziprasidone; or (2) FGA-any other antipsychotic medication. Outpatient services were defined as the proportion of 30-day periods of each medication episode with at least 1 behavioral health visit. Survival analyses were used to analyze the data, and they were adjusted for the baseline propensity for receiving an SGA.. Second-generation antipsychotic episodes were not associated with reduced arrests compared to FGA episodes; however, the interaction between outpatient services and SGA episodes was significant (hazard ratio [HR] = 0.68; 95% CI, 0.50-0.93; P = .02) such that an SGA episode with an outpatient visit during at least 80% of every 30-day period of the episode was associated with reduced arrests compared to SGA episodes with fewer outpatient services. There was no significant effect for concurrent FGA episodes and outpatient treatment (HR = 0.81; 95% CI, 0.60-1.10; P = .18). Substance use, poor refill compliance, and prior arrest increased risk of subsequent arrest.. The interaction between outpatient visits and treatment with SGAs was significantly associated with reduced arrests. These findings indicate the importance of concurrent antipsychotic medications and outpatient services to affect arrest outcomes for adults with schizophrenia and bipolar disorder.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Crime; Delayed-Action Preparations; Dibenzothiazepines; Female; Florida; Humans; Isoxazoles; Male; Medicaid; Middle Aged; Olanzapine; Outpatients; Paliperidone Palmitate; Piperazines; Propensity Score; Pyrimidines; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome; United States; Young Adult

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Follow-Up Studies; Humans; Isoxazoles; Middle Aged; Paliperidone Palmitate; Pyrimidines; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Isoxazoles; Paliperidone Palmitate; Pyrimidines; Schizophrenia

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Humans; Isoxazoles; Paliperidone Palmitate; Pyrimidines; Schizophrenia, Paranoid; Young Adult

A case of apparent seizure and atrial fibrillation associated with paliperidone is reported.. A 46-year-old man arrived at the emergency room (ER) via ambulance. Earlier that morning, his wife observed him awakening in a panic, drifting back to sleep, and then subsequently awakening in a panic with an apparent seizure lasting one to two minutes. The episode included tongue biting and urinary incontinence. His medical history included bipolar disorder, diabetes mellitus, hyperlipidemia, and hypertension. The patient's medications included metformin, insulin glargine, insulin lispro, simvastatin, enalapril, escitalopram, lamotrigine, and clonazepam and had not changed for many months except for the recent addition of paliperidone four days before his arrival at the ER. Electrocardiography revealed atrial fibrillation, a ventricular rate of 151 beats/min, a Q-Tc interval of 461 msec, and no significant changes in the ST segment or T wave. He had no chest pain, and all other laboratory test results and vital signs were normal. The patient was admitted for evaluation and given a single oral dose of potassium chloride. Diltiazem i.v. was administered with resultant conversion to normal sinus rhythm, after which the patient's heart rate and Q-Tc interval normalized. The patient was discharged after one day.. A man taking paliperidone and multiple other drugs experienced atrial fibrillation and a possible seizure. Although these are known adverse effects of atypical antipsychotics, it is unusual to have both events occur concurrently and with low-to-average dosages, and these events have not been associated with paliperidone in published case reports.

Topics: Antipsychotic Agents; Atrial Fibrillation; Bipolar Disorder; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Seizures

To compare serum concentrations of risperidone, 9-hydroxy (OH) risperidone and risperidone plus 9-OH risperidone, as well as the 9-OH risperidone/risperidone ratio in patients receiving depot and oral risperidone.. Serum concentrations from 78 patients receiving three different doses of risperidone depot were measured and compared with serum concentrations from 82 patients taking three different doses of oral risperidone.. Patients receiving risperidone depot had significantly lower serum concentrations of risperidone plus 9-OH risperidone than patients taking oral risperidone. More interestingly, the 9-OH risperidone/risperidone ratio was also significantly lower in patients receiving risperidone depot than in patients taking oral risperidone.. Serum concentrations of risperidone plus 9-OH risperidone may be a rather poor indication of the antipsychotic efficacy of risperidone unless their ratio is also considered.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Psychotic Disorders; Pyrimidines; Risperidone; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Breast Feeding; Female; Humans; Infant, Newborn; Isoxazoles; Milk, Human; Paliperidone Palmitate; Pregnancy; Pyrimidines; Risperidone