paliperidone-palmitate and Weight-Gain

Modeling dose-response relationships of drugs is essential to understanding their safety effects on patients under realistic circumstances. While intention-to-treat analyses of clinical trials provide the effect of assignment to a particular drug and dose, they do not capture observed exposure after factoring in nonadherence and dropout. We develop a Bayesian method to flexibly model the dose-response relationships of binary outcomes with continuous treatment, permitting multiple evidence sources, treatment effect heterogeneity, and nonlinear dose-response curves. In an application, we examine the risk of excessive weight gain for patients with schizophrenia treated with the second-generation antipsychotics paliperidone, risperidone, or olanzapine in 14 clinical trials. We define exposure as total cumulative dose (daily dose × duration) and convert to units equivalent to 100 mg of olanzapine (OLZ doses). Averaging over the sample population of 5891 subjects, the median dose ranged from 0 (placebo randomized participants) to 6.4 OLZ doses (paliperidone randomized participants). We found paliperidone to be least likely to cause excessive weight gain across a range of doses. Compared with 0 OLZ doses, at 5.0 OLZ doses, olanzapine subjects had a 15.6% (95% credible interval: 6.7, 27.1) excess risk of weight gain; corresponding estimates for paliperidone and risperidone were 3.2% (1.5, 5.2) and 14.9% (0.0, 38.7), respectively. Moreover, compared with nonblack participants, black participants had a 6.8% (1.0, 12.4) greater risk of excessive weight gain at 10.0 OLZ doses of paliperidone. Nevertheless, our findings suggest that paliperidone is safer in terms of weight gain risk than risperidone or olanzapine for all participants at low to moderate cumulative OLZ doses.

Topics: Adult; Antipsychotic Agents; Bayes Theorem; Dose-Response Relationship, Drug; Female; Humans; Male; Markov Chains; Medication Adherence; Middle Aged; Olanzapine; Paliperidone Palmitate; Risperidone; Schizophrenia; Weight Gain

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

Pharmacologic management strategies for schizophrenia, a relatively common psychotic disorder, include the use of typical and atypical antipsychotic drugs. In general, typical (or conventional) antipsychotics have a proven track record in effectively managing the positive symptoms of schizophrenia but sometimes lack efficacy in treating negative symptoms. The conventional agents are also associated with adverse neurologic effects such as extrapyramidal symptoms (EPS). The development of atypical antipsychotics has partly ameliorated the issue of EPS induced by typical antipsychotics. However, several of these atypical antipsychotic agents have been associated with adverse metabolic effects, including weight gain, dyslipidemia, and increased serum glucose levels. Paliperidone (9-hydroxy-riperidone) extended-release (ER) is an atypical antipsychotic indicated for the treatment of schizophrenia which utilizes a patented oral osmotic system technology that provides constant drug delivery over the course of the day. The efficacy and safety of paliperidone ER in patients with schizophrenia have been established. This review focuses on the metabolic safety of paliperidone ER in patients with schizophrenia. Clinical trials have demonstrated a lack of significant change in lipid profiles with paliperidone ER; furthermore, reported incidences of glucose-related adverse events in clinical trials were very low and similar to those seen with placebo. While dose-related increases in bodyweight of 1-2 kg have been observed with paliperidone ER, there are few reports of clinically relevant increases in bodyweight during treatment. Placebo-controlled trials indicate that the risk of developing metabolic disorders with paliperidone ER is low and similar to that seen with placebo. Furthermore, the ER formulation of paliperidone may offer potential advantages over atypical antipsychotics such as risperidone, particularly with regard to side effects and compliance, but comparative studies are needed.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Delayed-Action Preparations; Glucose; Humans; Isoxazoles; Paliperidone Palmitate; Pyrimidines; Schizophrenia; Weight Gain

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

To evaluate paliperidone palmitate 1-month formulation (PP1M) effectiveness in a naturalistic outpatient psychiatric setting.. We collected data from 50 outpatients affected by schizophrenia disorders treated with PP1M for 12 months in an Italian Mental Health Department. After analyzing selected demographic, clinical and pharmacological variables, we performed mirror analysis to compare psychiatric hospitalizations and urgent consultations required by the same patient 6 and 12 months before and after PP1M implementation (primary outcome). We analyzed clinical improvement in symptom (Clinical Global Impression-severity and improvement) and functioning (Global Assessment of Functioning) scales and drop-out rate during the 12-month PP1M treatment (secondary outcome). Data were statistically analyzed.. The mean PP1M dose was 93.5 mg (±27.7 SD) with a mean interval between each injection of 27.1 d (±4.5 SD). Twenty-three patients (46%) reported adverse effects (sexual dysfunctions, weight gain and extrapyramidal symptoms).Fifteen patients (30%) dropped out after 137.2 d (±103.1 SD) on average: six due to the lack of therapeutic adherence, six due to inefficacy and three due to adverse events. The drop-out patients presented more severe clinical profile in CGI-S and GAF scores at T0 in comparison with others. At mirror analysis, 12-month but not 6-month PP1M treatment statistically significantly reduced psychiatric hospitalizations (t = 2.3, p < .05) and urgent consultations (t = 2.1, p < .05). Both scale scores showed statistically significant improvement at T12 in comparison to T0.. This naturalistic study indicates that long-term PP1M treatment was safe and effective in preventing hospitalizations and urgent consultations as well as in improving clinical course.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Drug Compounding; Female; Hospitalization; Humans; Italy; Male; Medication Adherence; Middle Aged; Outpatients; Paliperidone Palmitate; Recurrence; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Adherence and Compliance; Treatment Outcome; Weight Gain

Paliperidone palmitate 3-monthly (PP3M) injectable formulation offers an advantage of improved medication adherence and lower relapse risk in patients with schizophrenia. This post hoc analysis compared outcomes following PP3M versus paliperidone palmitate 1-monthly (PP1M) treatment in patients with schizophrenia treated/untreated with oral risperidone/paliperidone (RIS/PALI).. Patients were treated with PP1M (50, 75, 100, or 150 mg equivalent [eq.]) for 17 weeks during an open-label (OL) phase and randomized (1:1) to PP3M (175, 263, 350, or 525 mg eq.) or PP1M (50, 75, 100, or 150 mg eq.) during a 48-week double-blind phase. Efficacy outcomes were compared based on prior oral RIS/PALI exposure: recent (≥ 28 days of oral RIS/PALI exposure with last dose within 14 days before study entry); or no (no oral RIS/PALI exposure within 60 days before study entry).. A total of 452 OL patients received recent oral RIS/PALI (n = 323 [71%], randomized to PP3M = 166; PP1M = 157), and 709 OL patients were without recent oral RIS/PALI (n = 506 [71%], randomized to PP3M = 254; PP1M = 252). Improvements in Positive and Negative Syndrome Scale (PANSS) scores (OL baseline-to-endpoint) were similar in recent-RIS/PALI (mean [standard deviation]:18.3 [17.96]) and no-RIS/PALI (- 21.1 [16.40]) subgroups. Relapse-free rates were comparable between recent-RIS/PALI (relapse-free rate [95% confidence interval for difference]: 2.6 [- 4.7 to 10.0]; PP3M: 90%; PP1M: 87%) and no-RIS/PALI subgroups (0.8 [- 4.5 to 6.0]; PP3M: 92%; PP1M: 91%). Weight gain was the most common (> 5% incidence) treatment-emergent adverse event in both subgroups irrespective of the prior treatment.. Patients with schizophrenia, irrespective of prior treatment with RIS/PALI, had comparable treatment outcomes and tolerability following PP3M or PP1M treatment.. This study is registered at the EU clinical trial registry (EudraCT Number: 2011-004889-15) and ClinicalTrials.gov (identifier: NCT01515423).

Topics: Administration, Oral; Adult; Antipsychotic Agents; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Paliperidone Palmitate; Psychiatric Status Rating Scales; Recurrence; Risperidone; Schizophrenia; Treatment Outcome; Weight Gain

Long-acting injectable antipsychotics (APs) are not well studied in recent-onset schizophrenia. This exploratory analysis of a study designed to reflect real-world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once-monthly paliperidone palmitate (PP) and daily oral APs in patients with recent-onset or chronic illness METHODS: This randomized, open-label, event monitoring board-blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351). Event-free probabilities were estimated using Kaplan-Meier method; hazard ratios (HRs) were estimated using Cox proportional hazard models. This subgroup analysis analysed data by disease duration (≤5 (recent-onset) or >5 years (chronic illness) since first psychiatric diagnosis).. Seventy-seven subjects met the criteria for recent-onset illness; 365 for chronic illness. HRs (95% CI) for treatment failure for oral APs versus PP were 1.73 (0.87-3.45; P = 0.121) for recent-onset and 1.37 (1.02-1.85; P = 0.039) for chronic illness. Most common adverse events for PP versus oral APs were injection site pain (recent-onset, 26% vs. 0%; chronic, 17% vs. 0%), increased weight (14% vs. 6%; 12% vs. 6%), akathisia (14% vs. 9%; 10% vs. 7%), insomnia (12% vs. 17%; 18% vs. 10%) and anxiety (12% vs. 6%; 10% vs. 8%).. Although neither pre-planned nor adequately powered, the estimated HRs suggest that the relative advantage of PP over oral APs for reducing the risk for treatment failure may be greater in patients with recent-onset schizophrenia than in those with more chronic illness.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Chronic Disease; Crime; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Paliperidone Palmitate; Schizophrenia; Single-Blind Method; Time-to-Treatment; Treatment Failure; Weight Gain; Young Adult

The purpose of this study was to conduct a post-hoc benefit-risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit-Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale, and Positive and Negative Syndrome Scale (PANSS). Safety outcomes were extrapyramidal symptom-related adverse events, weight gain, prolactin-related adverse events, somnolence, orthostatic hypotension, anticholinergic use, fasting plasma glucose, and total cholesterol/high-density lipoprotein. For the first 8 weeks of maintenance treatment, most efficacy outcomes significantly favored PP1M compared with paliperidone ER. Per 1000 patients, there would be 165, 115, 85, and 53 fewer cases of PSP worsening, relapse, PANSS worsening, and hospitalizations, respectively. For the first 40 weeks, PSP worsening significantly favored PP1M (140 fewer cases). Relapse, PANSS, hospitalizations, and Clinical Global Impression-Severity scale showed a consistent pattern favoring PP1M but were not significant. Safety outcomes for both 8-week and 40-week periods demonstrated no statistically significant differences between groups. These analyses suggest a benefit-risk profile favoring PP1M over oral paliperidone ER throughout 40 weeks of treatment, particularly in early treatment.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypotension; Injections, Intramuscular; Male; Paliperidone Palmitate; Risk Assessment; Schizophrenia; Tablets; Treatment Outcome; Weight Gain

To evaluate the efficacy, safety, and tolerability of paliperidone extended release (ER) relative to aripiprazole in adolescent schizophrenia.. In this multicenter, double-blind, phase 3 study (screening [≤3 weeks], with an acute treatment period [8 weeks] and a maintenance period [18 weeks]), adolescents (12-17 years old) with schizophrenia (DSM-IV diagnosis; Positive and Negative Symptom Score [PANSS] total score 60-120) were randomized (1:1) to once-daily paliperidone ER (6 mg per day [days 1-7], flexibly dosed 3, 6, or 9 mg per day from week 2 to end of study [EOS]), or to aripiprazole (2 mg per day [days 1 and 2], 5 mg per day [days 3 and 4], 10 mg per day [days 5-7], flexibly dosed 5, 10, or 15 mg per day [week 2 to EOS]).. Overall, 76% of enrolled patients (174/228) completed the study (paliperidone ER, 75% [85/113]; aripiprazole, 77% [89/115]). There was no significant difference in change in PANSS total scores from baseline to day 56 (primary endpoint) (paliperidone ER versus aripiprazole, -19.3 [13.80] versus -19.8 [14.56], p = .935); responders, 67.9% versus 76.3%, p = .119) and day 182 (-25.6 [16.88] versus -26.8 [18.82], p = .877; responders, 76.8% versus 81.6%, p = .444). All secondary endpoints (maintenance of clinical stability, change in PANSS-negative symptoms, Clinical Global Impression-Severity, and Personal and Social Performance scores) were similar in both treatment groups. The most common (>10% patients) treatment-emergent adverse events for paliperidone ER were akathisia, headache, somnolence, tremor, and weight gain, and for aripiprazole were worsening of schizophrenia and somnolence. Extrapyramidal symptoms including dystonia and hyperkinesia occurred in >2% in paliperidone ER-treated versus aripiprazole-treated patients.. Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating adolescent schizophrenia. Both drugs showed clinically meaningful improvements in symptom and functional measurements and were generally tolerable. Clinical Trial Registration Information-An Efficacy and Safety Study of Extended-Release (ER) Paliperidone in Adolescent Participants With Schizophrenia; http://clinicaltrials.gov; NCT01009047.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Europe; Female; Headache; Humans; India; Male; Paliperidone Palmitate; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Severity of Illness Index; Treatment Outcome; United States; Weight Gain

There is a strong association between weight gain and metabolic events in patients with schizophrenia receiving many of the second-generation antipsychotic agents. We explored the relationship between body mass index (BMI) and metabolic events in patients with schizophrenia receiving long-acting injectable paliperidone palmitate (PP) in a long-term trial.. We conducted a post hoc analysis of data from a PP study that included a 33-week open-label transition (TR) and maintenance phase; a variable duration, randomized, double-blind (DB), placebo-controlled phase and a 52-week open-label extension (OLE) phase. Overall, 644 patients received PP continuously from study entry through discontinuation or study completion and were grouped by baseline BMI (kg/m2): underweight (BMI <19; n = 29, 4.5%), normal-weight (BMI 19- < 25; n = 229, 35.6%), overweight (BMI 25- < 30; n = 232, 36.0%) and obese (BMI ≥ 30; n = 154, 23.9%). Metabolic treatment-emergent adverse events (TEAEs) and changes in related laboratory results from TR baseline were analyzed.. PP exposure was similar across BMI groups; overall mean (SD) dose/month was 70.3 (17.17) mg eq. [109.6 (26.78) mg]; median duration of exposure was 204 days (6 to 1009 days). Occurrences of metabolic TEAEs overall by group were 0% (underweight), 14.9% (normal-weight), 14.7% (overweight), and 24.0% (obese). The most common (≥ 2%) metabolic TEAE were weight gain and elevated blood levels of glucose, lipids, and insulin. Mean BMI and weight increased in normal-weight and overweight groups at DB endpoint, and in underweight, normal-weight and overweight groups at OLE endpoint (p ≤ 0.05). No consistent trend for increased metabolic-related laboratory values by baseline BMI group was observed. Homeostatic model assessments for insulin resistance indicated preexisting insulin resistance at baseline, with minimal changes at OLE endpoint across baseline BMI groups.. Occurrences of metabolic-related TEAEs trended with greater BMI status in patients with schizophrenia treated with PP; consistent trends in metabolic-related laboratory values were not observed.. This study is registered at ClinicalTrials.gov (NCT 00518323).

Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Double-Blind Method; Female; Humans; Isoxazoles; Lipids; Male; Middle Aged; Obesity; Paliperidone Palmitate; Palmitates; Schizophrenia; Weight Gain; Young Adult

Long-acting injectable antipsychotics are used to reduce medication nonadherence and relapse in schizophrenia-spectrum disorders. The relative effectiveness of long-acting injectable versions of second-generation and older antipsychotics has not been assessed.. To compare the effectiveness of the second-generation long-acting injectable antipsychotic paliperidone palmitate with the older long-acting injectable antipsychotic haloperidol decanoate.. Multisite, double-blind, randomized clinical trial conducted from March 2011 to July 2013 at 22 US clinical research sites. Randomized patients (n = 311) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a long-acting injectable antipsychotic.. Intramuscular injections of haloperidol decanoate 25 to 200 mg or paliperidone palmitate 39 to 234 mg every month for as long as 24 months.. Efficacy failure, defined as a psychiatric hospitalization, a need for crisis stabilization, a substantial increase in frequency of outpatient visits, a clinician's decision that oral antipsychotic could not be discontinued within 8 weeks after starting the long-acting injectable antipsychotics, or a clinician's decision to discontinue the assigned long-acting injectable due to inadequate therapeutic benefit. Key secondary outcomes were common adverse effects of antipsychotic medications.. There was no statistically significant difference in the rate of efficacy failure for paliperidone palmitate compared with haloperidol decanoate (adjusted hazard ratio, 0.98; 95% CI, 0.65-1.47). The number of participants who experienced efficacy failure was 49 (33.8%) in the paliperidone palmitate group and 47 (32.4%) in the haloperidol decanoate group. On average, participants in the paliperidone palmitate group gained weight and those in the haloperidol decanoate group lost weight; after 6 months, the least-squares mean weight change for those taking paliperidone palmitate was increased by 2.17 kg (95% CI, 1.25-3.09) and was decreased for those taking haloperidol decanoate (-0.96 kg; 95% CI, -1.88 to -0.04). Patients taking paliperidone palmitate had significantly higher maximum mean levels of serum prolactin (men, 34.56 µg/L [95% CI, 29.75-39.37] vs 15.41 µg/L [95% CI, 10.73-20.08]; P <.001, and for women, 75.19 [95% CI, 63.03-87.36] vs 26.84 [95% CI, 13.29-40.40]; P<.001). Patients taking haloperidol decanoate had significantly larger increases in global ratings of akathisia (0.73 [95% CI, 0.59-0.87] vs 0.45 [95% CI, 0.31-0.59]; P=.006).. In adults with schizophrenia or schizoaffective disorder, use of paliperidone palmitate vs haloperidol decanoate did not result in a statistically significant difference in efficacy failure, but was associated with more weight gain and greater increases in serum prolactin, whereas haloperidol decanoate was associated with more akathisia. However, the CIs do not rule out the possibility of a clinically meaningful advantage with paliperidone palmitate.. clinicaltrials.gov Identifier: NCT01136772.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Double-Blind Method; Female; Haloperidol; Hospitalization; Humans; Injections, Intramuscular; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Palmitates; Schizophrenia; Treatment Failure; Treatment Outcome; Weight Gain

There are no direct comparisons of paliperidone extended-release (ER), aripiprazole and ziprasidone in efficacy and metabolic influence in patients with first-episode schizophrenia.. The present study examined the efficacy and metabolic influence of paliperidone ER, aripiprazole and ziprasidone in patients with first-episode schizophrenia in China.. Subjects were recruited from outpatient and 254 patients entered the trial. These patients received treatment randomly with paliperidone ER, aripiprazole and ziprasidone and were assessed at baseline, 13, 26 and 52 weeks, respectively with Positive and Negative Syndrome Scale (PANSS), 7-item Clinical Global Impressions-Severity (CGI-S), anthropometric (weight, body mass index and waist circumference) and metabolic (fasting blood glucose, HbA1c, cholesterol, high density lipoproteins (HDL), low density lipoproteins and triglycerides) measures.. A total of 203 patients completed the trial. Paliperidone group had significant greater reduction in PANSS than aripiprazole group and ziprasidone group from 13 weeks, although the a reduction in PANSS of each group was more than 20%. There was no difference in CGI-S among the three groups, and all three groups had a significant reduction from baseline in CGI-S. Aripiprazole group increased in weight and body mass index despite no statistical change in waist circumference. Other two groups showed no changes in anthropometric measure. At the end of the study, two glucose metabolic indices (fasting blood glucose and HbA1c) of aripiprazole group were significantly higher than that of baseline. In lipid metabolism, aripiprazole group reduced triglycerides significantly and had no changes in other indices. Paliperidone group reduced HDL and increased triglycerides despite no changes in glucose metabolism. Ziprasidone group also had no significant changes in glucose metabolism, but reduced cholesterol, low density lipoproteins and increased HDL. Furthermore, 22 subjects in three groups reached the diagnostic criteria of metabolic syndrome.. Paliperidone ER, aripiprazole and ziprasidone are effective in treating first-episode schizophrenia, and the ranking of efficacy from high to low is paliperidone ER > aripiprazole > ziprasidone. Paliperidone ER can impair lipid metabolism potentially but had no influence on glucose metabolism. Aripiprazole can damage glucose metabolism and has little influence on lipid metabolism. Ziprasidone is considered an atypical antipsychotic with no evidence of harm to glucose and lipid metabolism.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Body Mass Index; China; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Female; Follow-Up Studies; Humans; Hyperglycemia; Hyperlipidemias; Isoxazoles; Male; Metabolic Diseases; Paliperidone Palmitate; Piperazines; Psychiatric Status Rating Scales; Pyrimidines; Quinolones; Schizophrenia; Thiazoles; Weight Gain; Young Adult

Recent evidence indicates that atypical antipsychotics represent a promising option for the treatment of autistic disorder. In particular, risperidone appears to be effective in treating aggressiveness, hyperactivity, irritability, stereotypies, social withdrawal, and lack of interests.. The aim of the present study was to evaluate the effectiveness and tolerability of risperidone in children with autistic disorder and to examine the correlation between plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and the clinical response.. The effect of treatment with risperidone (0.75-2 mg/day; mean +/- SD dose = 1.26 +/- 0.42 mg/day) was studied for 24 weeks in 20 children (14 boys, 6 girls) ages 3 to 10 years (mean age 6.0 +/- 2.4 years), diagnosed with autistic disorder. Fourteen items selected from the Children's Psychiatric Rating Scale (CPRS-14) and Clinical Global Impression (CGI) were used for behavioral evaluation. Patients were classified as responders if they showed a 25% or greater decrease on CPRS-14 total score at final evaluation compared with baseline and a final CGI rating of 1 or 2. Patients were rated for extrapyramidal side effects on the Abnormal Involuntary Movement Scale (AIMS). Other side effects, including the expected side effects of atypical antipsychotics drugs, were assessed by a checklist. Blood samples for determination of risperidone and its active metabolite 9-OH-risperidone were obtained after 12 weeks, and serum prolactin levels were measured on admission and at weeks 12 and 24.. The psychopathological state, as assessed by CPRS, improved significantly over the duration of treatment. The mean CPRS-14 scores decreased significantly from 63.7 +/- 10.0 at baseline to 52.9 +/- 14.3 at week 12 (p < 0.01). At the end of 12 weeks of treatment, 8 patients were considered responders, and 10 patients reached a minimal improvement. No further improvement was observed in the following 12 weeks. In all children, serum prolactin levels increased significantly (p < 0.001) from 166 +/- 88 UI/mL at baseline to 504 +/- 207 UI/mL at week 12 of risperidone treatment. Weight gain and increased appetite were the most common unwanted effects. A mean increase of 3.7 +/- 1.7 kg in body weight was observed at final evaluation as compared with baseline. There was no significant correlation between percent improvement in total CPRS score and the plasma level of risperidone's active fractions (the sum of the risperidone and 9-OH-risperidone plasma concentration).. This study provides further evidence of the beneficial effects of risperidone in children diagnosed with autistic disorder. However, the potential advantages of risperidone should be weighed against the risk of unwanted effects, such as an increase in serum prolactin levels and weight gain. No relation was observed between total plasma risperidone and 9-OH-risperidone concentrations and clinical response.

Topics: Autistic Disorder; Child; Child, Preschool; Drug Tolerance; Female; Humans; Isoxazoles; Male; Paliperidone Palmitate; Pyrimidines; Risperidone; Statistics, Nonparametric; Weight Gain

Long-acting injectable (LAI)antipsychotics are often used in psychosis to assist with medication compliance and relapse prevention, although the weight gain and metabolic effects in young people are yet to be examined. This study examined the long-term effects of aripiprazole and paliperidone in LAI formulation on weight gain and metabolic parameters in young people with early episode psychosis.. Weight gain and other metabolic effects of aripiprazole and paliperidone in LAI formulation were examined in 59 young people with early episode psychosis over a 12-month period. Changes in outcome measurements were examined at baseline and 3 monthly intervals.. The results showed that both aripiprazole and paliperidone were associated with time-dependent increases in weight. At 12 months, weight increased by an average of 7% (6 kg) with both aripiprazole and paliperidone relative to the baseline, and the percentage of overweight or obese people increased from 33% to 60%. There was no advantage of aripiprazole compared to paliperidone with regards to weight change, although aripiprazole was associated with lower triglycerides and prolactin levels.. Both LAI medications were associated with substantial weight increases over time. These results build on emerging evidence showing that aripiprazole is not weight neutral in young people. Our recommendation is that weight-management programs should be offered from the start of medication initiation.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Delayed-Action Preparations; Humans; Paliperidone Palmitate; Psychotic Disorders; Schizophrenia; Weight Gain

The aim of this study was to explore the effectiveness and tolerability of long-acting paliperidone palmitate antipsychotic in adolescent first-episode schizophrenia patients while comparing the results with the oral antipsychotic risperidone.. This study is a retrospective, noninterventional study to assess the effectiveness and tolerability of long-acting injectable antipsychotic paliperidone palmitate in first-episode adolescent patients during the first 12 months of treatment compared with the oral antipsychotic risperidone. The data include general sociodemographic characteristics, number of hospitalizations, side effects, and the following clinical scales: Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Clinical Global Impression Improvement and Severity (CGI-I and CGI-S), and Treatment Satisfaction Questionnaire for Medication (TSQM).. During the 12-month study period significant improvement was registered in patients receiving both paliperidone palmitate and risperidone in the following scales: PANSS, PSP, CGI-I, and CGI-S. Patients receiving paliperidone palmitate had significantly greater improvement in PANSS, CGI-S, and PSP compared with the risperidone group. Patients receiving risperidone had significantly higher number of hospitalizations than the patients receiving paliperidone palmitate. The TSQM revealed that the patients who were receiving paliperidone palmitate achieved significantly higher scores on the convenience scale, global satisfaction, and on the overall result, whereas no difference was observed on the effectiveness scale. There were several side effects reported for paliperidone (5.5% hyperprolactinemia, 5.5% weight gain) and risperidone (5.5% hyperprolactinemia, 16.7% weight gain).. In conclusion, paliperidone palmitate seems to be safe and effective in adolescent patients. Furthermore, it compared favorably with risperidone in the clinical response, side effects, and hospitalizations.

Topics: Adolescent; Antipsychotic Agents; Brief Psychiatric Rating Scale; Female; Hospitalization; Humans; Hyperprolactinemia; Male; Paliperidone Palmitate; Retrospective Studies; Risperidone; Schizophrenia; Weight Gain

We report a case of early onset schizophrenia that responded favourably to paliperidone but experienced hyperprolactinaemia, tremors, and weight gain, with impaired fasting glycaemia. Addition of bromocriptine helped with both hyperprolactinaemia and tremors, but also brought about euglycaemia and, strikingly, ameliorated negative symptoms.

Topics: Adolescent; Antipsychotic Agents; Bromocriptine; Humans; Hyperprolactinemia; Male; Paliperidone Palmitate; Schizophrenia; Treatment Outcome; Tremor; Weight Gain

Oral and long-acting injectable second-generation antipsychotics are known to be associated with a high risk of metabolic adverse effects. Together with other drug treatments, poor lifestyle choices, and genetic liability, they contribute to development of metabolic syndrome (MetS), which occurs in nearly one third of patients with schizophrenia.The primary objective of this multicenter prospective observational study was to explore the prevalence of MetS in a sample of 60 real-world patients treated with paliperidone palmitate (PP) over a period of 12 months. The secondary objectives were to assess other tolerability aspects and the efficacy of PP on schizophrenic symptoms.The proportion of patients with MetS at baseline (33%) did not significantly change neither at 6 (39.0%) nor at 12 months (29.5%) of PP treatment. The same applies to each individual component of MetS. We found a slight but statistically significant increase in body mass index (26.3 ± 6.0 vs 27.1 ± 4.6, P = 0.031) and of waist circumference (98.2 ± 17.9 vs 100.3 ± 15.9, P = 0.021) from baseline to end point. Weight gain was detected in approximately 15% of patients.At least 1 mild or moderate adverse event was found in 71.3%, 88.0%, and 52.1% of patients, respectively, at baseline, 6 months, and 12 months. A significant improvement in schizophrenic symptoms emerged by means of Positive and Negative Syndrome Scale total and subscale scores.Together with previous literature findings, our results seem to indicate that PP could be a valid therapeutic option for patients with a severe disorder and with a high metabolic risk profile.

Topics: Adult; Antipsychotic Agents; Cohort Studies; Female; Humans; Injections, Intramuscular; Male; Metabolic Syndrome; Middle Aged; Paliperidone Palmitate; Prospective Studies; Schizophrenia; Weight Gain

The aim of the present study is to test the efficacy of palmitate paliperidone long-acting injection for patients with borderline personality disorder (BPD). A total of 16 patients with BPD were treated with intramuscular paliperidone palmitate (IMPP) over 12 weeks. Effectiveness measures included the CGI-BPD, HARS, MADRS, BIS-11, and STAXI-2. Functional improvement was assessed using the Global Assessment of Functioning scale. A list of adverse events was provided to clinicians and patients. Treatment with IMPP was associated with a significant average reduction of 1.6 (95% confidence interval: 1192-2008; P>0.01) in CGI-BPD scores and an average increase of psychosocial functioning as scored by the Global Assessment of Functioning scale of 13.3 (95% confidence interval: 8.35-18.31; P>0.01) was obtained. The treatment decreased impulsive-disruptive behaviors and improved general functioning. An acceptable tolerance was observed. The average weight gain was clinically irrelevant despite being statistically significant. No other relevant adverse side effects were reported, with the exception of galactorrhea, which required suspension of treatment in three patients. IMPP seems to be a well-tolerated alternative to other second-generation antipsychotics in the treatment of BPD. More controlled studies replicating these results should be proposed in the future.

Topics: Adult; Antipsychotic Agents; Borderline Personality Disorder; Delayed-Action Preparations; Female; Humans; Injections, Intramuscular; Interpersonal Relations; Male; Middle Aged; Paliperidone Palmitate; Weight Gain

Antipsychotics have been used in the therapy of schizophrenia and bipolar disorder and several second generation antipsychotics (SGA) are already available in Hungary. The clinical trials' results are confusing in regarding the differences in the efficacy of the SGA's, but the differences in their side-effects are clear. Considering its most important side-effects, such as extrapyramidal symptoms, weight gain, metabolic syndrome and prolactin level elevation, quetiapine has a fairly good side effect profile, and can therefore be recommended especially in case of bipolar patients who are highly sensitive towards side effects.. In our case-report, we present four patients who were successfully treated with quetiapine for their psychotic mood elevation.

Topics: Adult; Affect; Antipsychotic Agents; Dibenzothiazepines; Drug Therapy, Combination; Euphoria; Female; Humans; Isoxazoles; Male; Medication Adherence; Middle Aged; Paliperidone Palmitate; Prolactin; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain