. 2007 Feb;3(1):13–39. doi: 10.2147/nedt.2007.3.1.13

Table 2.

Overview of clinical studies examining the efficacy and safety of long-acting injectable risperidone in special patient populations with schizophrenia

Study details	Treatment groups	Efficacy	Adverse events
Elderly patients
Lasser et al 2004c Elderly patients ³65 years (sub-analysis of Fleischhacker et al 2003)	LAR 25 mg, 50 mg, and 75 mg (n=57)	77% completed the study Mean (±SE) PANSS total scores improved from 73.0±2.1 at baseline to −10.5±1.5 at endpoint, p<0.001 Clinical improvement (³20% reduction in PANSS) was seen in 49% of patients CGI-S ratings of “not ill”, “very mildly ill”, or “mildly ill” increased from 28% at baseline to 69% at endpoint Significant mean score increases on SF-36 domains: mental component scale (+4.6, p<0.05), vitality (+6.1, p<0.05), social functioning (+9.6, p<0.01), and role-emotional (+14.7, p<0.05)	Incidence of AEs in respective treatment groups: 74%, 71%, 78% AEs occurring in >10% of patients: insomnia (14%), constipation (12%), bronchitis (12%), psychosis (11%), rhinitis (11%) Withdrawals due to AEs: 3.5% Mean subjective ESRS patient ratings decreased from 10.2±1.5 at baseline to −3.1± 0.8 at endpoint, p<0.001 Mean weight gain of 0.3±0.7 kg at endpoint for patients with available data (n=50) Patients’ mean (±SE) rating of pain at injection site decreased from 8.6±2.2 after first injection to 2.3±0.6 at endpoint, p<0.01
Young and first-episode patients
Emsley et al 2005 12-week, open-label interim analysis in patients with a first episode of schizophrenia	LAR 25 mg and 50 mg (n=20)	90% completed the study Mean improvement in PANSS total score at endpoint: −35.6±16; p<0.001 (all doses)	Incidence of AEs: 70% (all doses) Most frequently reported AEs (all doses): aggression (10%), extrapyramidal disorder (10%) Change in mean BMI: +2.7 kg (all doses)
Emsley et al 2006 6-month open-label interim analysis in patients with first episode psychosis	LAR 25 mg and 50 mg (n=51)	84% completed the study 1 patient withdrew due to insufficient response Total PANSS scores improved from 90.3± 13.8 at baseline to 53.1±14.7 at endpoint 74% of patients achieved a clinical response (³50% improvement in total PANSS) Five patients relapsed and 3 patients were hospitalized, once each	AEs were mainly mild-to-moderate (96%) 58% of AEs were judged unlikely related to LAR The most commonly reported AE was headache (23.9%) Serious AEs occurred in 3 patients (5.9%) ESRS scores were low at baseline and did not change significantly throughout the study Change in mean bodyweight: +3.6 kg
Lasser et al 2004d Younger adults (men £25 years; women £30 years) with schizophrenia or schizoaffective disorder (sub-analysis of Fleischhacker et al 2003)	LAR 25, 50, and 75 mg (n=100)	58% completed the study 9% withdrew due to insufficient response 3% withdrew due to non-compliance Mean (±SD) improvement in PANSS total scores at endpoint (all doses): −9.8±1.7, p<0.001 Clinical improvement (³20% reduction in PANSS) was seen in 62% of patients CGI-S ratings of “not ill”, “very mild”, and “mild” increased from 39% at baseline to 60% at endpoint	No unexpected AEs (data not provided) Most commonly reported AEs: insomnia (27%), psychosis (22%), anxiety (21%), depression (17%), rhinitis (15%) Withdrawals due to AEs: 7% Patient ratings of pain decreased from 23.3±21.7 at baseline to 14.4±18.3 at endpoint
Saleem et al 2004 Young patients, 18–30 years (sub-analysis of Möller et al 2005)	LAR 25, 37.5, and 50 mg (n=119)	68% completed the study 9% withdrew due to insufficient response 4.2% withdrew due to noncompliance Significant improvement in mean (±SD) PANSS total score at endpoint, p<0.001 (all doses; data not provided) Clinical improvement (³20% reduction in PANSS) occurred in 30% of patients (all doses) CGI-S ratings of “not ill” or borderline ill” increased from 6% at baseline to 30% at endpoint (all doses) Overall trend towards an improvement in HRQoL as assessed by the SF-36 9% of patients rated their treatment as “very good” at baseline compared with 29% at endpoint (all doses)	No unexpected AEs (data not provided) Mean score for dyskinesia was reduced from 0.8±1.8 at baseline to 0.5±1.6 at endpoint (all doses) at 1 month and these improvements persisted to endpoint 4 patients had a prolactin related AE (all doses) 1 patient had a glucose-related AE (all doses)
Parellada et al 2005 Patients in early phases of schizophrenia/schizoaffective disorder agents (sub-analysis of Möller et al 2005)	LAR 25, 37.5, and 50 mg (n=382)	73% completed the study 4% withdrew due to insufficient response 3% withdrew due to noncompliance PANSS total score decreased by 11.3±19.1 from baseline to endpoint; p<0.0001 (all doses) Clinical improvement (³20% reduction in PANSS) occurred in 40% of patients (all doses) CGI-S ratings of “borderline mentally ill” increased from 12% at baseline to 26% at endpoint 18 patients (5%) were newly hospitalized Significant improvements in all SF-36 subscale scores at endpoint (except vitality), pd”0.001 Mean GAF score improved from 57.6±6.5 at baseline to 65.3±18.3 at endpoint, p£0.0001 (all doses) 9% expressed their satisfaction with treatment as “very good” at baseline compared with 30% at endpoint	Incidence of AEs: 69% (all doses) Incidence of serious AEs: 14% (all doses) Withdrawals due to AEs: 6% (all doses) AEs occurring in ³3% of patients (all doses): insomnia (7%), disease exacerbation (6%), depression (5%), anxiety (5%), weight gain (4%), relapse (3%), headache (3%) Mean total ESRS score at endpoint: from 5.2 to 2.6, p£0.001 Change in mean bodyweight: +1.8 kg Change in BMI: +0.6 kg/m² 6 patients (2%) reported injection site pain 1 patient reported (0.3%) had new onset diabetes mellitus
Schizoaffective disorder
Mohl et al 2005 Symptomatically stable patients with schizoaffective disorder (sub-analysis of Möller et al)	LAR 25, 37.5, and 50 mg (n=249)	74% completed the study 4% withdrew due to insufficient response 3% withdrew due to non-compliance Significant reduction in mean (±SD) PANSS total score at endpoint, p<0.001 (data not provided) Uncontrolled hostility/excitement scores improved from 7.6±3.8 at baseline to 6.9±3.8 at endpoint Anxiety/depression scores improved from 10.4±4.1 at baseline to 8.7±3.9 at endpoint Mean scores for CGI-S fell throughout the study (data not provided) Mean GAF score improved from 59.4±15.6 at baseline to 66.4±17.7 at endpoint, p<0.001 (all doses) Significant improvements in the SF-36 domains of: Social functioning (7.9 points), role emotional (19.6 points), Mental Health (7.9 points), all p<0.001 78% rated their treatment with LAR to be either “good” or “very good”	Incidence of AEs: 66% Incidence of serious AEs: 17% AEs occurring in >5% of patients: anxiety (11%), weight gain (8%) and insomnia, headache, disease exacerbation (6% each) Incidence of EPS: 13% Mean (±SD) change in total ESRS score at endpoint: −2.7±5.9, p<0.001 Change in mean bodyweight: +1.4 kg Change in BMI: +0.5 kg/m² 1 patient (0.4%) experienced a glucose related AE (new onset diabetes mellitus) 2 patients (0.8%) reported an injection related AE
Lasser et al 2004b Symptomatically stable patients with schizoaffective disorder (sub-analysis of Fleischhacker et al 2003)	LAR 25 mg (n=27) LAR 50 mg (n=42) LAR 75 mg (n=41)	67.3% completed the study 8% discontinued due to insufficient response in the 25 mg group Mean (±SE) improvement in PANSS total score at endpoint: −9.0±1.6 p<0.001 Mean (±SE) improvement in anxiety/depression at endpoint: −1.3±0.4, p<0.001 Mean (±SE) improvement in uncontrolled hostility/excitement: −0.7±0.3, p<0.05 Clinical improvement (³20% reduction in PANSS) was seen in 57.7% of patients CGI-S ratings of “not ill”, “very mildly ill”, or “mildly ill” increased from 54.7% at baseline to 79.2% at endpoint, p<0.002	No unexpected AEs (data not provided) AEs occurring in ³10% of patients: insomnia (36%), anxiety (30%), depression (25%), psychosis (25%), headache (16%) Withdrawals due to AEs: 4% Mean (±SD) patient ESRS self-ratings decreased from 3.7±4.1 at baseline to 2.8±4.2 at endpoint, p<0.05 Change in mean bodyweight: +2.5 kg Injection site pain, as indicated by median score on the VAS decreased from 11 at baseline to 4 at endpoint Injection site pain was absent in 67% of patients at the first injection and 83% of patients at the last injection
Obese patients
Teijeiro et al 2004 Obese patients with a BMI of ³30 kg/m² (sub-analysis of Möller et al 2005)	LAR 25, 37.5, and 50 mg (n=119)	74% completed the study 4% withdrew due to insufficient response Significant improvement in mean (±SD) PANSS total score at endpoint, p<0.05 (data not provided) Clinical improvement (³20% reduction in PANSS) occurred in 30% of patients (all doses) CGI-S ratings of ‘not ill’ increased from 6% at baseline to 16% at endpoint (all doses)	No unexpected AEs (data not provided) Change in mean bodyweight: +0.5 kg (all doses) Change at endpoint in total ESRS score: −2.0, p=0.0001 (all doses)
Patients of different ethnicity
Ciliberto et al 2005 Patients classified as white, black and other (sub-analysis of Kane et al 2003)	LAR 25, 50, and 75 mg (n=439)	43% completed the study Significant effect of treatment (ANCOVA, p<0.001), but not race (ANCOVA, p=0.392), on improvement in PANSS total scores at endpoint CGI-S ratings of “not ill”, “very mildly ill”, or “mildly ill” increased regardless of racial group	Incidence of AEs – white group: LAR 84%, placebo 83%; black group: LAR 80%, placebo 90%; other group: LAR 80%; placebo 71% Withdrawals due to AEs – white group: LAR 16%, placebo 14%; black group: LAR 7%, placebo 11%; other group, LAR 16%, placebo 6% Most commonly reported AEs were headache, insomnia, agitation, psychosis, anxiety (data not provided) Mean change in subjective ESRS scores at endpoint – white group: LAR −0.55±3.1, placebo −0.04± 2.4; black group: LAR 0.03±2.9, placebo−0.18± 2.7; other group: LAR −0.82±2.8, placebo −1.9±4.0 Change in mean bodyweight at endpoint – white group: LAR +1.55 kg, placebo −0.54 kg; black group: LAR +2 kg, placebo +0.39 kg; other group LAR +1.61 kg, placebo −2.69 kg

Abbreviations: AE, adverse event; ANCOVA, Analysis of Covariance; BMI, body mass index; CGI-S, Clinical Global Impression-Severity; DAI, Drug Attitude Inventory; EPS, extrapyramidal symptoms; ESRS, Extrapyramidal Symptoms Rating Scale; GAF, Global Assessment of Function; HRQoL, health-related quality of life; LAR, long-acting risperidone; PANSS, Positive and Negative Syndrome Scale for Schizophrenia; SD, standard deviation; SE, standard error; SF-36, Short Form-36; VAS, visual analogue scale.