| Short-term studies |
Kane et al 2003
12-week, double-blind, placebo- controlled study in patients with schizophrenia Run-in with oral risperidone
|
Placebo (n=98)
LAR doses included:
25 mg (n=99)
50 mg (n=103)
75 mg (n=100) |
68% of placebo patients and 51%–52% of LAR patients discontinued the study Withdrawals due to insufficient response: LAR 25 mg, 22%; LAR 50 mg, 15%; LAR 75 mg, 12%; placebo, 30% Withdrawals due to non-compliance: LAR 25 mg 0%; LAR 50 mg, 3%; LAR 75 mg, 3%; placebo 4% Mean (±SD) improvement in PANSS scores at endpoint: LAR 25 mg, −6.2±16.9; LAR 50 mg, −8.5±16.9; LAR 75 mg, −7.4±16.9; placebo, 2.6±16.9 Clinical improvement (320% reduction in PANSS) occurred in 47%, 48%, 39%, and 17% of patients in the LAR 25 mg, 50 mg, 75 mg, and placebo groups, respectively, p<0.001 |
Incidence of AEs: LAR 25 mg, 80%; LAR 50 mg, 83%; LAR 75 mg 82%; placebo, 83% Incidence of serious AEs in respective groups: LAR 25 mg, 13%; LAR 50 mg, 14%; LAR 75 mg, 15%; placebo, 24% AEs occurring in 35% of patients: LAR–headache (20%), agitation (15%), insomnia (15%), psychosis (12%), anxiety (9%); placebo – agitation (25%), psychosis (23%), anxiety (15%), insomnia (14%), headache (12%) Withdrawals due to AEs: LAR 25 mg, 11%; LAR 50 mg, 12%; LAR 75 mg, 14%; placebo, 12% Incidence of EPS: LAR 25 mg, 10%; LAR 50 mg, 24%; LAR 75 mg, 29%; placebo, 13% Mean change in total ESRS at endpoint: LAR 25 mg, −1.5±4.0; LAR 50 mg, 0.1±3.6; LAR 75 mg 0.0±5.3; placebo, −0.1±4.8 Change in mean bodyweight: LAR 25 mg, +0.5 kg; LAR 50 mg, +1.2 kg; LAR 75 mg, +1.9 kg; placebo −1.4 kg 80%, 81%, 84%, 90% of patients in the LAR 25 mg, 50 mg, 75 mg, and placebo groups rated injection site pain as absent after the sixth injection |
|
Lauriello et al 2005
|
LAR 25 mg (n=52)
LAR 50 mg (n=57)
LAR 75 mg (n=52)
Placebo (n=53) |
35% completed the study Withdrawals due to insufficient response: LAR (all doses), 23%; placebo, 36% Mean (±SE) improvement in PANSS scores at endpoint: LAR (all doses) −9.27±1.44; placebo 0.72±2.59; p<0.001 Clinical improvement (320% reduction in PANSS) occurred in 50% of patients in the LAR group (all doses) and 27% patients in the placebo group; p=0.012 CGI scores of “not ill”, “very mild”, or “mild” occurred in 32% of patients in the LAR group(all doses) and 5% of patients in the placebo group, p=0.0023 |
Most commonly reported AEs with LAR (all doses): headache (25%), agitation (22%), psychosis (17%), insomnia (17%), dyspepsia (15%) Withdrawals due to AEs: LAR (all doses) 14%, placebo 11% Incidence of EPS: LAR 25 mg, 12%; LAR 50 mg, 21%; LAR 75mg, 37%; placebo 15% Change in mean bodyweight at endpoint: LAR (all doses), +2.3 kg; placebo, −0.4 kg Patient-reported injection site pain at endpoint: LAR (all doses), 12.3±20.01; placebo, 6.71±12.81 |
|
Lindenmayer et al 2005
|
LAR 25 mg (n=52)
LAR 50 mg (n=57)
LAR 75 mg (n=52)
Placebo (n=53) |
Data previously presented by Kane et al 2003
|
Mean (±SD) VAS scores at first and final injections: LAR 25mg, 11.8±14.4 (first) and 10.0±12.4 (final); LAR 50 mg 16.3±21.9 (first) and 13.6±21.7 (final); LAR 75 mg, 16.0±17.9 (first) and 9.6±16.0 (final, p<0.01); placebo, 15.6±20.7 (first) and 12.5±18.3 (final) Investigators rated redness, swelling, and induration after the first injection as absent in 96%–100% of assessments Investigators rated pain as absent in 79%–85% of assessments Five (2%) of 250 assessments of pain were rated as moderate or severe by the investigator |
Lindenmayer et al 200412-week, open-label study in symptomatically stable patients with schizophrenia switched from oral haloperidol (n=46), oral quetiapine (n=45), or oral olanzapine (n=50)
|
LAR 25 mg, 37.5 mg, and 50 mg (n=141) |
81% completed the study 4% withdrew due to insufficient response 2% withdrew due to noncompliance Mean (±SD) improvement in PANSS scores at endpoint: −1.9±0.6 (all doses) Clinical improvement (320% reduction in PANSS) occurred in 37% of patients (all doses) CGI-S ratings of “very mild” to “mild” increased from 43% at baseline to 61% at endpoint |
Incidence of AEs: 81% (all doses), 83% (previous haloperidol), 84% (previous quetiapine), 76% (previous olanzapine) AEs occurring in 310% of patients: insomnia (16%), headache (15%), agitation (11%), psychosis (11%), anxiety (9%) Withdrawals due to AEs: 4% (all doses), 7% (previous haloperidol), 2% (previous quetiapine), 2% (previous olanzapine) Incidence of EPS: 8% (all doses), 15% (previous haloperidol), 4% (previous quetiapine), 4% (previous olanzapine) Change in mean bodyweight: +0.4 kg (all doses), +1.4 kg (previous haloperidol), +0.3 kg (previous quetiapine), −0.5 kg (previous olanzapine) Change in glucose levels: from 6.2 mmol/L at baseline to 5.8 mmol/L at endpoint (all doses) Change in triglycerides: from 2.3 mmol/L at baseline to2.0 mmol/L (all doses) Mean (±SE) serum prolactin concentrations increase from 23.5±2.4 ng/mL at baseline to 52.2±3.7 ng/mL at endpoint(all doses) 10 patients (7%) reported hyperprolactinemia One patient reported mild pain at the injection site |
Turner et al 2004
12-week, open-label study in symptomatically patients with schizophrenia switched from depot conventional antipsychotics: flupenthixol (n=41), fluphenazine (n=33), haloperidol (n=50), and zoclopenthixol (n=42) No run-in with oral risperidone
|
LAR 25 mg, 37.5 mg, and 50 mg (n=166) |
92% completed the study 2 patients withdrew due to insufficient response Mean (±SE) improvement in PANSS scores at endpoint: −3.4±1.0, p<0.001 (all doses) Clinical improvement (320% reduction in PANSS) occurred in 48% of patients (all doses) CGI-S ratings of “not ill” to “mild” increased from 52% at baseline to 64% at endpoint |
Incidence of AEs: 58% (all doses), 68% (previous flupenthixol), 52% (previous fluphenazine), 54% (previous haloperidol), 57% (previous zuclopenthixol) Incidence of serious AEs (all doses): 8% AEs occurring in 310% of patients: psychosis (13%), hyperprolactinemia (11%), insomnia (10%), headache (7%), rhinitis (7%) Withdrawals due to AEs (all doses): 1% Incidence of EPS: 3% (all doses) Median change in total ESRS at endpoint: −2.0 (all doses) Change in mean bodyweight: +1.0 kg (all doses) Change in BMI: +0.3 kg/m2 all doses) |
|
Chue et al 2005
|
Oral risperidone 2, 4, and 6 mg/day (n=321)
LAR 25, 50, and 75 mg (n=319) |
Patients completing the study: oral risperidone, 84%; LAR, 80% Withdrawals due to insufficient response: oral risperidone, 2.5%; LAR, 3.8% Mean (±SE) improvement in PANSS scores at endpoint: oral risperidone, −6.3±0.7; LAR, −5.4± 0.7, p<0.001 for each Percentage of patients rated as “not ill” or with “mild illness” increased from 46.9% in the oral risperidone group and 49.2% in the LAR group at baseline to 57.8% and 57.9%, respectively, at endpoint |
Incidence of AEs: oral risperidone 60%, LAR 61% AEs occurring in 35% of patients • oral risperidone: insomnia (9%), anxiety (7%), headache (7%), psychosis (5%); LAR: anxiety (10%), insomnia (10%), headache (8%), psychosis (5%) Withdrawals due to AEs: oral risperidone, 4.7%; LAR, 5.6% Incidence of EPS: oral risperidone, 6%; LAR, 7% Change in mean bodyweight: oral risperidone, +0.3 kg; LAR, +0.5 kg AEs potentially related to prolactin: oral risperidone, 2.5%; LAR, 1.3% Decrease in prolactin levels from baseline to endpoint: oral risperidone group, 38.9±1.6 ng/mL to 38.0±1.8 ng/mL; LAR group, 37.4±1.7 ng/mL to 32.6±1.6 ng/mL Pain at injection site was low (mean scores of 18–20 on a 100 point VAS) |
| Long-term studies |
|
Rodriguez et al 2005
|
LAR 25 mg and 50 mg (n=323) |
51.4% completed the study Mean (±SD) improvement in PANSS scores at endpoint –LAR 25 mg: 66.8±16.4 at baseline to 62.3±16.7 at endpoint; LAR 50 mg: 66.1±16.5 at baseline to 60.6±17.5 at endpoint Clinical improvement (320% reduction in PANSS) occurred in 27.7% of patients on LAR 25 mg and 34.8% of patients on LAR 50 mg |
Withdrawal due to AEs: 6% Most commonly reported AEs: insomnia (28%), psychotic disorder (20%), headache (19%), anxiety (16%) Mean (SD) subjective ESRS patient ratings from baseline to endpoint: LAR 25 mg, from 2.1 to 1.8; LAR 50 mg, from 2.0 to1.6; p<0.005 Weight remained unchanged: baseline (89.2±22.44) to endpoint (90.1±23.08) |
Möller et al 2005
24-week, open-label study in symptomatically stable patients with schizophrenia switched directly from other oral or long-acting antipsychotics No run-in with oral risperidone
|
LAR 25 mg, 37.5 mg, and 50 mg (n=1876) |
74% completed the study 4% withdrew due to insufficient response 2.9% withdrew due to noncompliance Mean (±SD) PANSS total score improved from 73.4±22.3 at baseline to 63.1±22.8 at endpoint, p<0.001 (all doses) Clinical improvement (320% reduction in PANSS) occurred in 38% of patients (all doses) CGI-S scores improved from 3.9±1.1 at baseline to 3.3±1.3 at endpoint, p<0.001 (all doses) CGI-S ratings of “borderline ill/not ill” increased from 11% at baseline to 28% at endpoint (all doses) Mean GAF score improved from 56.3±16.5 at baseline to 63.2±18.3 at endpoint, p<0.001 (all doses) Significant improvements (>5 points) for the role physical, bodily pain, general health, social functioning, role emotional and mental health factors of the SF-36, p30.001 Patient satisfaction improved from 3.2±0.9 at baseline to 3.9±1.0 at endpoint, p<0.001 |
Incidence of AEs: 72% (all doses) Most commonly reported AEs: anxiety (7%), insomnia (7%), exacerbation of disease (6%) Withdrawals due to AEs: 6% (all doses) Incidence of EPS: 12% Mean change in total ESRS at endpoint: −1.5 (patients switched from atypical antipsychotic); −4.8 (patients switched from long-acting conventional agent); −2.5 (patients switched from oral conventional agent); p<0.001 Change in mean bodyweight: +0.9 kg (all doses) Glucose-related AEs: 5 (0.3%) patients; 3 (0.2%) case of new- onset diabetes 27 patients (1%) reported injection site pain |
|
Vauth et al 2004
|
LAR 25, 37.5, and 50 mg (n=119) |
67% completed the study 8% withdrew due to insufficient response 4% withdrew due to noncompliance Significant reduction in mean PANSS total score at endpoint, p<0.001 (all doses, data not provided) Clinical improvement (320% reduction in PANSS) occurred in 31% of patients (all doses) CGI-S ratings of “not ill” increased from 2% at baseline to 14% at endpoint (all doses) Overall trend towards an improvement in HRQoL as assessed by the SF-36 |
No unexpected AEs (data not provided) Withdrawals due to AEs: 9% Significant reduction in total ESRS scores at endpoint, p<0.001 (data not provided) |
|
Gastpar et al 2005
|
LAR 25, 37.5, and 60 mg (n=192) |
70% completed the study 5% withdrew due to insufficient response 4% withdrew due to noncompliance Mean (±SD) PANSS total scores improved from 74.0±21.5 at baseline to 65.8±21.4 at endpoint, p=0.0001 (all doses) Clinical improvement (320% reduction in PANSS) occurred in 32% of all patients CGI-S ratings of “not ill” or “borderline ill” increased from 10% at baseline to 21% at endpoint Mean GAF score improved from 55.7±16.6 at baseline to 61.4±20.1 at endpoint, p=0.0001 Significant improvements in all SF-36 domains except role physical, bodily pain and physical component summary 6% expressed their satisfaction with treatment as “very good” at baseline compared with 31% at endpoint |
Incidence of AEs: 72% (all doses) Withdrawals due to AEs: 6% (all doses) Most commonly reported AEs: anxiety (12%), disease exacerbation (10%), insomnia (9%), depression (6%), akathisia(5%) No change in bodyweight or BMI from baseline to endpoint Mean change in ESRS subscale scores at endpoint: subjective parkinsonism symptoms, −0.6 (p=0.003); CGI for clinical severity of parkinsonism, −0.3 (p=0.0006); hyperkinesias, −0.4 (p=0.0005); hypokinesia, −0.8 (p=0.0001) |
|
Kissling et al 2005
|
LAR 25, 37.5, and 50 mg (n=715) |
71% completed the study 2.7% withdrew due to insufficient response 1.3% withdrew due to non-compliance Mean (±SD) PANSS total score decreased from 74.9±22.7 at baseline to 59.7±21.9 at endpoint, p<0.001 Clinical improvement (320% reduction in PANSS) occurred in 47% of patients Percentage of patients who meet the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint Percentage of patients who met the PANSS severity criteria for remission 36 months increased from 24% at month 6 to 45% at endpoint |
Incidence of AEs: 72% Incidence of serious AEs: 20% Withdrawals due to AEs: 3% Most commonly reported AEs: anxiety (12%), insomnia (10%), weight gain (8%), depression (7%), headache (5%) Change in mean bodyweight: +1.4 kg Change in BMI +0.5 kg/m2 Two patients (0.3%) had a glucose-related AE: one patient had new-onset diabetes mellitus and one had hyperglycemia Nine patients (1%) reported AEs associated with injection site pain |
Fleischhacker et al 2003
1-year, open label study in symptomatically stable patients with schizophrenia switched from other oral or long-acting antipsychotics Run-in with oral risperidone
|
LAR 25 mg (n=120)
LAR 50 mg (n=228)
LAR 75 mg (n=267) |
65% completed the study 7.8% withdrew due to insufficient response 1.8% withdrew due to non-compliance Mean (±SE) improvement in PANSS scores at endpoint (all doses): −6.1±0.7, p<0.01 Clinical improvement (320% reduction in PANSS) was seen in 49% of patients: 55% of the 25 mg group, 56% of the 50 mg group, and 40% of the 75 mg group CGI-S ratings of “not ill”, “very mildly ill”, or “mildly ill” increased from 58% at baseline to 78% at endpoint in the 25 mg group, from 40% to 65% in the 50 mg group, and from 33% to44% in the 75 mg group 18% of patients were rehospitalized during the study |
Incidence of AEs in respective treatment groups: 82%, 84%, 87% Withdrawals due to AEs in respective treatment groups: 4%, 6%, 5% Most commonly reported AEs: anxiety (24%), insomnia (21%), psychosis (17%), depression (15%), headache (12%) Incidence of EPS: LAR 25 mg, 21%; LAR 50 mg, 27%; LAR 75 mg, 25% Incidence of tardive dyskinesia: 0.7% Mean (SE) change in total ESRS at endpoint (all doses): −2.5±0.2 Change in mean bodyweight: LAR 25 mg, +1.7 kg; LAR 50 mg, +2.6 kg; LAR 75 mg, +1.9 kg Patients with no injection site pain (all doses): 68% at first injection; 80% at last injection |
|
van Os et al 2004
|
LAR 25 mg (n=18)
LAR 50 mg (n=16)
LAR 75 mg (n=12) |
61% completed the study 2.2% withdrew due to insufficient response 2% withdrew due to noncompliance Mean PANSS total scores improved from 73.1±17.2 at baseline to 64.5±18.2 at endpoint, p=0.0006 Clinical improvement (320% reduction in PANSS) occurred in 49% of patients CGI-S ratings of “not ill”, “very mild”, or “mild” increased from 27% at baseline to 52% at endpoint |
Incidence of AEs: 54% Most commonly reported AEs: anxiety (26%), insomnia (22%), hyperkinesia (17%), depression (15%), psychosis (15%) Withdrawals due to AEs: 13% Mean (±SD) subjective ESRS patient rating improved from 3.1±4.7 at baseline to 1.4±2.2 at endpoint p=0.0173 -
Mean (±SD) objective ESRS physician rating of parkinsonism
improved from 7.8±9.9 at baseline to 3.8±5.7 at endpoint, p<0.003
Injection site pain decreased from 14.93± 19.59 at baseline to 6.44±14.72 at endpoint, p=0.0041 |
|
Lasser et al 2004a
|
LAR 25 mg (n=35)
LAR 50 mg (n=80)
LAR 75 mg (n=73) |
66.5% completed the study 5% withdrew due to insufficient response Mean PANSS scores improved from 64.2±18.9 at baseline to 58.2±20.3 at endpoint, p<0.001 Clinical improvement (320% reduction in PANSS) occurred in 52% of patients: CGI-S ratings of “not ill”, “very ill”, or “mild” increased from 47.4% at baseline to 67.0% at endpoint |
Incidence of AEs: 90% Most commonly reported AEs: anxiety (29%), psychosis (19%), headache (18%), insomnia (18%) Withdrawals due to AEs: 5.6% Incidence of EPS: 9% Mean (±SD) subjective ESRS patient rating improved from 4.9±4.2 at baseline to 2.8±3.8 at endpoint, p<0.001 Mean (±SD) objective ESRS physician ratings of parkinsonism improved from 10.4±10.3 at baseline to 5.3±7.2 at endpoint, p<0.001 Change in mean bodyweight: +2.4 kg Change in BMI: +1.2 kg/m2 Mean VAS of pain after injection decreased from 21.42±23.3 at baseline to 13.9±20.8 at endpoint, p<0.001 |
|
Lasser et al 2005a
|
LAR 25 mg (n=79)
LAR 50 mg (n=125)
LAR 75 mg (n=132) |
66.4% completed the study 8% of patients withdrew due to insufficient response Mean (±SE) PANSS total scores improved from 64.5± 17.7 at baseline to 58.8±19.9 at endpoint, p<0.001 Clinical improvement (320% reduction in PANSS) was seen in 49.7% of patients CGI-S ratings of “not ill”, “very mildly ill”, or “mildly ill” increased from 13.8% at baseline to 32.9% at endpoint, p<0.0001 |
Incidence of AEs: 81% Most commonly reported AEs: insomnia (24%), anxiety (22%), depression (19%), worsening of psychosis (18%) Withdrawals due to AEs: 3.9% Incidence of EPS at Months 10–12: 4% Mean (±SD) subjective ESRS patient ratings improved from 2.7±3.1 at baseline to 1.8±2.4 at endpoint, p<0.001 Mean (±SD) objective ESRS physician rating of parkinsonism improved from 5.9±7.3 at baseline to 4.8±7.4 at endpoint, p<0.005 Change in mean bodyweight: +2.5 kg Change in BMI: +0.8 kg/m2 Average rating of pain severity decreased from 18.0±1.9 mm at first injection to 11.0±1.6 mm at endpoint |
|
Gharabawi et al 2005
|
LAR 25, 50, and 75 mg (n=662) |
Data previously presented by Fleischhacker et al 2003
|
Incidence of emergent tardive dyskinesia in respective treatment groups: 0.88%, 1.04%, and 0.89% Mean (±SD) physician’s examination for dyskinesia improved from 6.9±4.6 at baseline to 4.1± 4.3 at endpoint, p<0.001 Mean (±SD) CGI of dyskinesia score improved from 3.0±1.3 at baseline to 1.8±1.4 at endpoint, p<0.001 |
|
Lindenmayer et al 2005
|
LAR 25 mg (n=120)
LAR 50 mg (n=228)
LAR 75 mg (n=267) |
Data previously presented by Fleischhacker et al 2003
|
Mean (±SD) VAS scores at first and final injections: LAR 25 mg, 17.9±22.2 (first) and 9.5±16.7 (final, p<0.0001); LAR 50 mg, 18.1±19.7 (first) and 10.4±14.8 (final, p<0.0001); LAR 75 mg, 18.5±21.6 (first) and 13.6±19.9 (final, p=0.0001) Investigators rated redness, swelling and induration after the first injection as absent in 95–99% of assessments Investigators rated pain as absent in 79%–85% of assessments 22 (4.3%) of 416 assessments of pain were rated as moderate or severe by the investigator Mean DAI ratings indicated high patient satisfaction throughout the trial (baseline=7.30; endpoint=7.70, p<0.0001) |
|
Lasser et al 2005b
|
LAR 25, 50, and 75 mg (n=578) |
68.2% did not meet the symptom-severity remission criteria at baseline 20.8% of non-remitted patients achieved symptom remission for at least 6 months In patients who met the severity component of the remission criteria, mean (±SD) PANSS total scores improved from 66.0±14.6 at baseline to 47.8±10.9 at endpoint, p<0.0001 In patients who met the symptom component of the remission criteria, CGI-S ratings of “not ill”, “very mild”, or “mild” increased from 39% at baseline to 88% at endpoint, p<0.0001 Of the 31.8% who met the symptom-severity component of remission at baseline, 84.8% maintained these criteria at endpoint |
Incidence of AEs: 87.4% Most commonly reported AEs in patients meeting the remission criteria: insomnia (25%), anxiety (24.5%), psychosis (15.8%), depression (15.7%), headache (14.7%) |
|
Kushner et al 2004
|
LAR 25, 50, and 75 mg (n=271) |
25% completed the study 9% withdrew due to insufficient response 5% withdrew due to non-compliance Mean CGI-S were reduced by a mean of 0.7 points CGI-S ratings of “marked-severe” decreased from 86% at baseline to 46% at endpoint, p<0.002 |
AEs occurring in 310% of patients: psychosis (31%), headache (28%), insomnia (26%), agitation (24%), rhinitis (21%) Withdrawals due to AEs: 16% Incidence of EPS: LAR 25–50 mg, 28%; LAR 75 mg, 39% Median change in total ESRS at endpoint: −1.0 Change in mean bodyweight: +3.3 kg |
