paliperidone-palmitate and Basal-Ganglia-Diseases

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

Balancing tolerability and efficacy of medications can be problematic for clinicians when assessing appropriate therapy for patients. For antipsychotic therapy, this can be especially challenging because of the hazardous movement and metabolic effects associated with them. Paliperidone is an atypical antipsychotic used for the treatment of schizophrenia and schizoaffective disorder. A systematic review of the literature for the tolerability of the drug, paliperidone, was performed. A total of 15 articles met the criteria for inclusion representing a total of 3779 patients. Data combination was conducted using the Mantel-Haenszel method, random effects model at 95% confidence. Adverse events with the greatest incidence in the paliperidone population were any treatment emergent adverse event (68%), extra-pyramidal symptoms (23%), headache (14%), insomnia (11%), somnolence (9%), tachycardia (9%) and weight gain (8%). Reported events most likely related to paliperidone [largest attributable risks (AR)] were extra-pyramidal symptoms (AR=10), reduction in acute psychosis (AR=8), any treatment emergent adverse event (AR=6), tachycardia (AR=4), and weight gain (AR=4). Events where incidence was entirely because of paliperidone (incidence equals AR) were hypersalivation (3), dysarthria (2), and sexual dysfunction (1). Reported events totally unrelated to paliperidone (AR=0) included anxiety, asthenia, constipation, depression, dyspepsia, glucose related events, and vomiting. Overall, a 50% reduction in treatment emergent psychosis was seen in schizophrenic patients treated with paliperidone, however the reduction of a psychotic event is about equal to the occurrence of an adverse event with paliperidone.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Female; Humans; Isoxazoles; Male; Paliperidone Palmitate; Psychotic Disorders; Pyrimidines; Randomized Controlled Trials as Topic; Schizophrenia

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

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Female; Haloperidol; Humans; Hyperprolactinemia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate (PP) in the treatment of schizophrenia. Patients were randomized to receive gluteal injections of placebo or PP (50 or 100 mg eq., fixed doses), without oral supplementation, on days 1, 8, and 36 (9-wk, double-blind phase) in this phase 2b study. Patients (n=197, intent-to-treat analysis set) were 62% men, mean (s.d.) age 39 (10) yr, with a baseline mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total score of 87.0 (12.5). Mean (s.d.) PANSS total scores showed significant improvement at endpoint (primary measure) for both the PP 50 mg eq. [-5.2 (21.5)] and PP 100 mg eq. [-7.8 (19.4)] groups, vs. placebo [6.2 (18.3)] (p0.001, each dose vs. placebo). This improvement was detected by day 8 and maintained to endpoint (p0.011) for both doses. In the safety analysis set (n=247), fewer PP-treated patients (2%) discontinued for treatment-emergent adverse events vs. placebo-treated (10%). Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo, with the exception of parkinsonism-related disorders (50 mg eq. 5%, 100 mg eq. 8%, placebo 1%). Results of other safety measures suggest PP to be generally well-tolerated. Throughout the study, investigators rated injection-site pain as absent (56-71%), mild (24-39%), moderate (2-12%), or severe (0-2%). PP (50 and 100 mg eq. doses) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Double-Blind Method; Female; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Palmitates; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p< or =0.006) and PANSS negative and positive symptom Marder factor scores (p< or =0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5-6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Body Mass Index; Body Weight; Case-Control Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Delivery Systems; Evidence-Based Medicine; Female; Humans; Injections; Isoxazoles; Kaplan-Meier Estimate; Male; Middle Aged; Paliperidone Palmitate; Palmitates; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome

The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.. In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.. Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.. Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Young Adult

Assessment of the relation between oral risperidone dose, serum drug levels and clinical response may provide important information for rational treatment decisions. Inter-individual differences in the liver cytochrome P450 system, especially in the CYP2D6 subsystem, which account for a significant portion of risperidone metabolism, may also influence plasma drug levels and alter clinical response parameters. We thus prospectively investigated risperidone serum concentrations in relation to clinical efficacy and side-effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters.. Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6-week open dose clinical trial. Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS to assess medication side effects; and blood draws to quantify steady state plasma levels of risperidone and 9-OH-risperidone were carried out. In addition, major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped.. Eighty-two patients were recruited. Mean oral dose of risperidone was 4.3 +/- 0.9 mg. Mean plasma level of both risperidone and 9-OH-risperidone together ("active moiety") was 41.6 +/- 26.6 ng/ml. Significant improvements in PANSS scales and the various subscales ensued. There was a positive linear correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015) and between risperidone and 9-OH-risperidone levels (r = 0.262; p = 0.016). Nonresponders to pharmacotherapy (PANSS-Improvement < 30%) showed significantly higher active moiety plasma levels (49.9 +/- 30.7 ng/ml) than responders (38.2 +/- 17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601). Patients with longer illness duration (> or = 3 years) had significantly higher plasma drug levels than those with a shorter course (< 3 years; p = 0.039). Extrapyramidal side effects (EPS) and plasma levels were not correlated (r = 0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4. CYP2D6 polymorphisms did not predict clinical response, but predicted a tendential increase in the plasma risperidone to 9-OH-risperidone ratio (0.5 +/- 0.6 vs. 1.9 +/- 1.8; p = 0.120).. The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9-OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses. The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy, but affected risperidone to 9-OH-risperidone ratios. Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects. Conversely, the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances. Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration. The high inter-individual variability in risperidone and 9-OH-risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinically relevant active moiety.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Female; Genotype; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Prospective Studies; Psychiatric Status Rating Scales; Pyrimidines; Risperidone; Schizophrenia

Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date.. To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH-risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder.. Forty-two patients (30 males, 12 females, age 24-60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline.. Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n = 28) and non-responders (n = 14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs = -0.187, NS), 9-OH-risperidone (rs = 0.246, NS), and active moiety (rs = 0.249, NS). Active moiety concentrations in plasma were higher (P < 0.001) in patients developing clinically significant parkinsonian symptoms (n = 7) than in those with minimal (n = 7) or no drug-induced parkinsonism (n = 28).. In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Chromatography, High Pressure Liquid; Chronic Disease; Female; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Psychiatric Status Rating Scales; Pyrimidines; Risperidone; Schizophrenia; Schizophrenic Psychology

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Child; Drug Monitoring; Humans; Paliperidone Palmitate; Psychotic Disorders; Risperidone; Schizophrenia

It is generally held that the elderly are more sensitive to motor side effects of antipsychotics, although the mechanisms for such an effect are not fully understood. The objective of this study was to examine whether this sensitivity is due to a central pharmacokinetic (i.e., higher occupancy for a given plasma level) or pharmacodynamic (i.e., greater functional effects for a given occupancy) effect.. Cross-sectional.. Centre for Addiction and Mental Health, Toronto, Ontario, Canada.. Thirteen subjects aged 50 (mean +/- standard deviation age: 62 +/- 9 years) with schizophrenia or schizoaffective disorder who were receiving risperidone.. Dopamine D2 binding potential in the striatum, using [C]raclopride positron emission tomography scan. D2 receptor occupancy was calculated, using age-corrected measure from healthy individuals and region of interest analysis.. The authors observed the expected nonlinear relationship between total risperidone and 9-hydroxyrisperidone plasma level and striatal D2 receptor occupancy. The estimated plasma level of risperidone plus 9-hydroxyrisperidone associated with 50% maximal receptor occupancy was 7.3 ng/mL, which is similar to what has been reported in younger patients. However, extrapyramidal side effects (EPS) were observed in seven subjects at D2 occupancy of 34%-79%, occupancy levels that are lower than previously reported for younger patients in whom EPS are rare at occupancies lower than 80%.. The observation of greater functional effect (EPS in this case) for a given drug occupancy than the younger patients supports a pharmacodynamic mechanism for age-related antipsychotic drug sensitivity. This finding has important implications for dosing of antipsychotics in older patients with schizophrenia.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Case-Control Studies; Cross-Sectional Studies; Dopamine Antagonists; Female; Humans; Isoxazoles; Male; Middle Aged; Ontario; Paliperidone Palmitate; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychotic Disorders; Pyrimidines; Raclopride; Receptors, Dopamine D2; Risperidone; Schizophrenia; Treatment Outcome

Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks.. After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [(11)C]raclopride PET to measure D(2) occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone.. Mean post- and preinjection D(2) occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration associated with 50% D(2) occupancy (ED(50)) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D(2) occupancy.. All three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Brain; Carbon Radioisotopes; Corpus Striatum; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injections; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Positron-Emission Tomography; Prolactin; Psychotic Disorders; Pyrimidines; Raclopride; Receptors, Dopamine D2; Risperidone; Schizophrenia

In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Caffeine; Catecholamines; Central Nervous System Stimulants; Cotinine; Cues; Cytochrome P-450 CYP2D6; Female; Homovanillic Acid; Humans; Isoxazoles; Male; Methoxyhydroxyphenylglycol; Middle Aged; Paliperidone Palmitate; Polymorphism, Genetic; Psychiatric Status Rating Scales; Pyrimidines; Risperidone; Schizophrenia; Smoking

In the present study, we attempted to predict the risk of extrapyramidal side effects of a selective monoaminergic antagonist, risperidone, by analyzing the correlation between the dopamine D(2) receptor occupancy and the degree of extrapyramidal side effects of the drug. The occupancies of D(2) and 5-HT(2) receptors at various doses of risperidone were calculated by means of a receptor occupancy theory. The extrapyramidal side effects after administration of risperidone were attempted to predict by theoretical analysis of the correlation between the calculated occupancies and the evidence of extrapyramidal symptoms using a ternary complex model. The pharmacokinetic/pharmacodynamic analysis utilized the data concerning the pharmacokinetics of risperidone and 9-hydroxyrisperidone (active metabolite), their binding affinities with D(2) and 5-HT(2) receptors, and the clinical evidence of extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale: ESRS), gathered from the literature. The mean occupancy of 5-HT(2) receptors after the administration of regular doses of risperidone was suggested to be more than 90%, whereas the mean occupancy of D(2) receptors varied between 50-80%, depending on the dose. The correlation between the occupancy of D(2) receptors and the extrapyramidal symptoms could be successfully analyzed with a ternary complex model, showing the predictability of the model for the extrapyramidal side effects of risperidone. Since the estimated risk of the extrapyramidal side effects varied with the dose, the present method of predicting the extrapyramidal side effects of risperidone may provide a basis for developing a rational dosing regimen for the drug.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Dopamine Antagonists; Humans; Isoxazoles; Models, Biological; Paliperidone Palmitate; Pyrimidines; Receptors, Dopamine D2; Risperidone