Summary

• In a randomized, double-blind, noninferiority study, in all patients treated with RISPERDAL CONSTA, overall mean Positive and Negative Syndrome Scale (PANSS) total scores were 83.5 at baseline and 65.6 at endpoint (mean change -17.9), while the treatment effect in obese patients (Body Mass Index (BMI) ≥30 kg/m²) receiving RISPERDAL CONSTA was -17.5. There was a mean increase in body weight at endpoint of 1.0 kg.^1,2
• Significant symptom improvement at all assessment time points was observed on the PANSS for stable adult patients with a BMI ≥30 kg/m², who participated in a 6-month trial with RISPERDAL CONSTA. Body weight remained stable throughout the 6-month period with a mean change from baseline to endpoint of 0.5 kg. There was no significant change in mean BMI.³

PRODUCT LABELING

Please refer to the following section of the enclosed Full Prescribing Information which is relevant to your inquiry: ADVERSE REACTIONS.

CLINICAL STUDIES

Pandina et al (2009)^{1, 2} presented results from a 13-week, randomized, double-blind, noninferiority study of flexible doses of paliperidone palmitate (n=607) and RISPERDAL CONSTA (n=613) in the treatment of schizophrenia. Injections of RISPERDAL CONSTA (25-50 mg) were administered in the gluteal muscle with a 2-inch needle. At baseline, 43% of RISPERDAL CONSTA patients had a normal BMI (<25 kg/m²), 34% were overweight (25-<30 kg/m²), and 24% were obese (≥30 kg/m²). In all patients treated with RISPERDAL CONSTA, overall mean PANSS total scores were 83.5 at baseline and 65.6 at endpoint (mean change -17.9), while the treatment effect in obese patients (BMI ≥30 kg/m²) receiving RISPERDAL CONSTA was -17.5. There was a mean increase in body weight at endpoint of 1.0 kg in the RISPERDAL CONSTA group.

Teijeiro et al (2004)³ presented a sub-group analysis of obese patients with schizophrenia or other psychotic disorders in the Switch to Risperidone Microspheres (StoRMi) trial (n=119). The StoRMi trial⁴ investigated the maintained efficacy, safety, and tolerability of RISPERDAL CONSTA in adult patients switched directly from oral or depot antipsychotics without an oral risperidone run-in. Patients were required to be symptomatically stable on antipsychotic therapy for at least one month before trial entry. Patients were required to have a BMI of ≥30kg/m² to be included in this analysis.

RISPERDAL CONSTA 25 mg was injected intramuscularly into the gluteal muscle every two weeks for 6 months. The dose could be increased to 37.5 mg or 50 mg every 2 weeks after 2-4 weeks. All patients continued their previous antipsychotic regimen for the first 3 weeks of RISPERDAL CONSTA treatment.

Efficacy was measured at baseline and after months 1, 3 and 6 using the PANSS total and Clinical Global Impression (CGI). Global Assessment of Functioning (GAF) and patient satisfaction were evaluated at baseline and after six months. Safety was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) and by measuring body weight, vital signs and adverse events at baseline and after months 1, 3 and 6.

Sixty-five patients (55%) were male and 54 patients (45%) were female with a mean age of 44 years. The mean body weight at baseline was 98 kg (range 68-134, SD 13) and mean BMI at baseline was 34 kg/m² (range 30-45 kg/m², SD 3). The majority of patients had schizophrenia (73%) or schizoaffective disorder (20%).

Out of thirty-two patients (27%) who discontinued the study, five patients reported insufficient response as the reason.⁵ At Month 1, mean scores for the total PANSS were significantly reduced (P<0.05) from baseline and significant improvements continued at all assessments throughout the trial including endpoint. Significant improvements were seen also seen from baseline to endpoint in the PANSS negative and general psychopathology subscales, and in the PANSS five factors analysis for negative symptoms, disorganized thoughts, and anxiety/depression. There was a significant improvement from baseline to endpoint in CGI. The number of patients considered to be ‘not ill’ at endpoint was 16% compared with 6% at baseline. An improvement in GAF was seen with a mean of 60 at baseline (range 25-95, SD 16) to 64 (range 1-100, SD 21) at endpoint. A significant improvement in patient satisfaction was also seen from baseline to endpoint.

Body weight remained stable throughout the 6-month period with a mean change from baseline to endpoint of 0.5 kg (range -18 to +23 kg, SD 5; P=0.1638). There was no significant change in mean BMI. The total ESRS score improved significantly from baseline (mean 7, range 0-28,  SD 7) at Month 1 (mean 5, range 0-28, SD 6; P=0.0001), and these improvements were also seen at endpoint (mean 4, range 0-24, SD 5; P=0.0001).⁵ The majority of patients were initiated on RISPERDAL CONSTA 25 mg and approximately half received this dose throughout the study.

CASE REPORT

Brietzke et al (2011)⁶ presented a case of a 43-year-old woman with Bipolar II disorder and a BMI of 46.0 kg/m². After undergoing roux-en-Y bypass surgery, the patient developed severe gastrointestinal symptoms, such as postprandial nausea and vomiting. The patient could no longer tolerate previous medications she had been on, including oxcarbazepine, valproate, lamotrigine, ziprasidone, quetiapine, aripiprazole, and oral risperidone. During the next year, these medications were attempted again, however, their irregular administration were associated with three episodes of hypomania and persistent subsyndromal depressive symptoms. The patient was started on RISPERDAL CONSTA with a maintenance dose of 25 mg every 2 weeks. This treatment produced satisfactory control of the patient's acute hypomanic symptoms and prevented new episodes for a one year period.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 14 June 2023.