Efficacy of Long-acting Injectable Risperidone in Acute and Stable Patients with Schizophrenia: Prior Anti-Psychotic Use, and Relapse

This work was sponsored by Indivior Inc.This study was funded by Teva Pharmaceuticals. Background and Aims: Depression is a prevalent comorbidity associated with migraine and the burden of both disorders can decrease quality of life. UNITE examined the efficacy of fremanezumab in reducing depression in patients with migraine and major depressive disorder (MDD). Methods: In this 12-week, double-blind, parallel-group study (NCT04041284), adults with migraine and MDD with active moderate-to-severe depression were randomized (1:1) to monthly fremanezumab (225 mg) or placebo. Patients in the 12-week open label extension (OLE) received quarterly fremanezumab (675 mg). Exclusion criteria: bipolar disorder, psychotic features, catatonia, or suicidality. One concomitant medication for depression was permitted if the dose was stable ≥8 weeks prior to screening, with no changes anticipated. Key endpoints: mean change from baseline in symptoms of depression measured by the 17-item Hamilton Depression Rating Scale (HAMD-17) and Patient Health Questionnaire-9 (PHQ 9). Results: Among 353 patients randomized (mean age 42.9 years; 88% female), 330 completed the double-blind period. Mean change from baseline in HAMD-17 score was –6.0 versus –4.6 at Week 8 (P=0.0205), and –6.7 versus –5.4 at Week 12 (P=0.0228) for fremanezumab and placebo, respectively. Mean change from baseline in PHQ 9 score was –7.1 versus –5.8 at Week 8 (P=0.0283) and –7.8 versus –6.3 at Week 12 (P=0.0108) for fremanezumab and placebo, respectively. Reductions were maintained throughout the OLE. Conclusion: The statistically significant reduction in HAMD-17 scores, and clinically meaningful reductions in PHQ-9 scores, indicate that fremanezumab may reduce the symptoms and cumulative burden of migraine and depression.This study was funded by Teva Pharmaceuticals. Background and Aims: Depression is a prevalent comorbidity associated with migraine and the burden of both disorders can decrease quality of life. UNITE examined the efficacy of fremanezumab in reducing depression in patients with migraine and major depressive disorder (MDD). Methods: In this 12-week, double-blind, parallel-group study (NCT04041284), adults with migraine and MDD with active moderate-to-severe depression were randomized (1:1) to monthly fremanezumab (225 mg) or placebo. Patients in the 12-week open label extension (OLE) received quarterly fremanezumab (675 mg). Exclusion criteria: bipolar disorder, psychotic features, catatonia, or suicidality. One concomitant medication for depression was permitted if the dose was stable ≥8 weeks prior to screening, with no changes anticipated. Key endpoints: mean change from baseline in symptoms of depression measured by the 17-item Hamilton Depression Rating Scale (HAMD-17) and Patient Health Questionnaire-9 (PHQ 9). Results: Among 353 patients randomized (mean age 42.9 years; 88% female), 330 completed the double-blind period. Mean change from baseline in HAMD-17 score was –6.0 versus –4.6 at Week 8 (P=0.0205), and –6.7 versus –5.4 at Week 12 (P=0.0228) for fremanezumab and placebo, respectively. Mean change from baseline in PHQ 9 score was –7.1 versus –5.8 at Week 8 (P=0.0283) and –7.8 versus –6.3 at Week 12 (P=0.0108) for fremanezumab and placebo, respectively. Reductions were maintained throughout the OLE. Conclusion: The statistically significant reduction in HAMD-17 scores, and clinically meaningful reductions in PHQ-9 scores, indicate that fremanezumab may reduce the symptoms and cumulative burden of migraine and depression. Introduction RBP-7000 is a once-monthly subcutaneous extended-release risperidone formulation approved for treatment of schizophrenia in adults. In this secondary analysis, we assessed RBP-7000 in acute and stable patients over one year. Methods Data are from two Phase III studies: an 8-week inpatient double-blind, randomized, placebo-controlled study of adult patients with acute exacerbation of schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score 80-120 inclusive, RCT Nf337; RBP-7000 90mg n=111, 120mg n=114, placebo n=112), NCT02109562; followed by a 52-week outpatient open-label study (OLS) of RBP-7000 120mg in stable patients who completed the RCT (rollover patients, Nf92) or de novo patients (PANSS total score ≤70, Nf408), NCT02203838. Relapse was defined by increases from baseline on scores from the Clinical Global Impression-Severity scale and the PANSS, hospitalization for psychosis and suicidality. One-year relapse rates were estimated using Kaplan-Meier method. Results Most patients were male (76.6% RCT; 67.4% de novo) and 41-50 years old (38.3% RCT, 31.4% de novo). The most commonly used (≥10%) prior antipsychotic treatments were aripiprazole, olanzapine, quetiapine, and risperidone. RCT patients showed continued improvement in PANSS and de novo patients remained stable throughout the OLS. Relapse occurred in 8 (8.7%, relapse rate 11.7%) of RCT patients and 22 (5.4%, relapse rate 7.3%) of de novo patients. Conclusion This secondary analysis showed both continued improvement for rollover patients and stability for de novo patients in PANSS total scores, and low relapse rates, illustrating the efficacy of RBP-7000 injections over one year.