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Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval.

Gharabawi GM, Gearhart NC, Lasser RA, Mahmoud RA, Zhu Y, Mannaert E, Naessens I, Bossie CA, Kujawa M, Simpson GM - Ann Gen Psychiatry (2007)

Bottom Line: There were no unexpected safety and tolerability findings.Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients.Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Roche Pharmaceuticals, Nutley, NJ, USA. GGharaba@JANUS.JNJ.com

ABSTRACT

Background: Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder.

Methods: Clinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations.

Results: Twelve patients in the intent-to-treat population (n = 67) met relapse criteria (17.9%). Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS) and clinical status (CGI-S) at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%), anxiety (16.1%), insomnia (16.1%), and headache (11.5%). There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study.

Conclusion: Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely managed with long-acting risperidone 50 mg once monthly, these findings alone do not identify which patients will have a sufficient therapeutic benefit nor do they quantify comparative effects of standard and altered dosing. Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results. Controlled studies would be required to support a recommendation for alternative dosing regimens.

No MeSH data available.


Related in: MedlinePlus

Mean (± SD) plasma concentrations of risperidone plus 9-hydroxyrisperidone by study week. Pharmacokinetic (PK) analyses are based on 771 samples from 87 patients. Intensive pharmacokinetic data are based on 7 samples planned between weeks 24 and 28 (1 every 4 days) from 18 patients.
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Figure 3: Mean (± SD) plasma concentrations of risperidone plus 9-hydroxyrisperidone by study week. Pharmacokinetic (PK) analyses are based on 771 samples from 87 patients. Intensive pharmacokinetic data are based on 7 samples planned between weeks 24 and 28 (1 every 4 days) from 18 patients.

Mentions: The pharmacokinetic analysis of risperidone plus 9-hydroxyrisperidone was based on data from 771 samples from 87 patients. Mean plasma concentrations for risperidone plus 9-hydroxyrisperidone were generally stable throughout the study (Figure 3). During steady state, obtained with samples from 18 patients, the average plasma concentration of risperidone plus 9-hydroxyrisperidone was 17.5 (6.1) ng/mL, and the fluctuation index was 199% (55.8) (Table 3).


Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval.

Gharabawi GM, Gearhart NC, Lasser RA, Mahmoud RA, Zhu Y, Mannaert E, Naessens I, Bossie CA, Kujawa M, Simpson GM - Ann Gen Psychiatry (2007)

Mean (± SD) plasma concentrations of risperidone plus 9-hydroxyrisperidone by study week. Pharmacokinetic (PK) analyses are based on 771 samples from 87 patients. Intensive pharmacokinetic data are based on 7 samples planned between weeks 24 and 28 (1 every 4 days) from 18 patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1803785&req=5

Figure 3: Mean (± SD) plasma concentrations of risperidone plus 9-hydroxyrisperidone by study week. Pharmacokinetic (PK) analyses are based on 771 samples from 87 patients. Intensive pharmacokinetic data are based on 7 samples planned between weeks 24 and 28 (1 every 4 days) from 18 patients.
Mentions: The pharmacokinetic analysis of risperidone plus 9-hydroxyrisperidone was based on data from 771 samples from 87 patients. Mean plasma concentrations for risperidone plus 9-hydroxyrisperidone were generally stable throughout the study (Figure 3). During steady state, obtained with samples from 18 patients, the average plasma concentration of risperidone plus 9-hydroxyrisperidone was 17.5 (6.1) ng/mL, and the fluctuation index was 199% (55.8) (Table 3).

Bottom Line: There were no unexpected safety and tolerability findings.Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients.Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Roche Pharmaceuticals, Nutley, NJ, USA. GGharaba@JANUS.JNJ.com

ABSTRACT

Background: Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder.

Methods: Clinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations.

Results: Twelve patients in the intent-to-treat population (n = 67) met relapse criteria (17.9%). Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS) and clinical status (CGI-S) at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%), anxiety (16.1%), insomnia (16.1%), and headache (11.5%). There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study.

Conclusion: Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely managed with long-acting risperidone 50 mg once monthly, these findings alone do not identify which patients will have a sufficient therapeutic benefit nor do they quantify comparative effects of standard and altered dosing. Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results. Controlled studies would be required to support a recommendation for alternative dosing regimens.

No MeSH data available.


Related in: MedlinePlus