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Psychiatric Inpatient Healthcare Resource Utilization and Treatment Patterns Among Patients With Predominant Negative Symptoms in Schizophrenia
- Rashmi Patel, Darshan Mehta, Aditi Kadakia, Yida Won, Carole Dembek, Gwilym Williams, Xueyan Huang, Courtney Zeni, Andrei Pikalov
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, pp. 222-223
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Introduction
Currently approved treatments for schizophrenia (antipsychotics) have demonstrated effectiveness for treating positive symptoms; however, these agents are largely ineffective in treating other domains. Negative symptoms, including avolition, alogia, blunted affect, and asociality, are difficult to treat, and often persist despite adequate control of positive symptoms. Additionally, some patients experience “predominant” (moderate-to-severe negative symptoms that have greater relative severity than co-occurring positive symptoms) or “prominent” (severity of negative symptoms [moderate-to-severe] without any reference to positive symptoms) negative symptoms. These symptoms are known to have great impact on patient social functioning and quality of life, and are associated with poorer clinical course and outcomes for patients. Here, we examined inpatient healthcare resource utilization in patients with schizophrenia experiencing predominantly negative symptoms (PNS).
MethodsDe-identified data were extracted from electronic health records in the NeuroBlu Database across 25 US mental healthcare providers. Positive and negative symptom data were derived from free-text records using natural language processing. PNS was defined as the presence of three or more negative symptoms and three or fewer positive symptoms at first clinical contact following schizophrenia diagnosis. Groups were balanced for baseline demographic and clinical characteristics by minimizing the generalized Mahalanobis distance and compared using chi-square and t-tests. Treatment patterns were visualized using Sankey diagrams.
ResultsA total of 4444 patients with schizophrenia were identified and 8% were classified as PNS. A balanced cohort of 720 patients (50% PNS) was generated. Patients with PNS were more likely to be hospitalized in the 12 months following diagnosis (PNS: 76%, non-PNS: 60%, χ2: 22.5, p < 0.001) and were switched to a second-line antipsychotic after a shorter first-line treatment duration. The most frequently prescribed antipsychotics differed between groups (PNS: risperidone, aripiprazole, haloperidol; non-PNS: risperidone, olanzapine, other atypical).
DiscussionThis study demonstrates that negative symptoms in schizophrenia may be associated with worse illness course and higher healthcare resource utilization. There remains a need for new treatment options for patients with persistent, prominent, or predominant negative symptoms which specifically improve this historically hard-to-treat and assess symptom domain.
FundingSunovion Pharmaceuticals, Inc.
Efficacy and Safety of Lurasidone in a Younger Population With Bipolar Depression: Pooled Post-hoc Analysis of Two Placebo-controlled Studies
- Chris Davey, Aswin Ratheesh, Michael Tocco, Yongcai Mao, David George;, Andrei Pikalov, Manpreet K Singh
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- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, p. 248
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Introduction
Early onset of bipolar disorder is associated with high rates of psychiatric comorbidity (e.g., anxiety disorders, ADHD, PTSD), high rates of recurrence, and marked impairment in functioning and quality of life. The aim of this analysis was to evaluate the efficacy and safety of lurasidone in bipolar depression in youth and young adult patients (10–30 years old).
MethodsData from two 6-week, double-blind, placebo-controlled studies of lurasidone monotherapy for bipolar I depression were pooled for this analysis. In the 1st study, patients 10–17 years old were evaluated using the Children’s Depression Rating Scale–Revised (CDRS-R) and the Clinical Global Impression-Bipolar Severity (CGI-BP-S) depression scale; in the 2nd study, a subgroup of adult patients (18–30 years old) were evaluated by CGI-BP-A, and the MADRS, with the latter being converted to a CDRS-R scores using a validated conversion algorithm.
ResultsThe safety population consisted of 465 patients (mean age, 17.1 years; mean age of onset, 14.1; mean CDRS-R total score, 60.8). 400 patients (85.7%) completed the study. For lurasidone vs. placebo, LS mean Week 6 change was -21.4 vs. -15.3 for the CDRS-R total score (P<0.0001; ES, 0.46); and -1.6 vs. -1.1 for the CGI-BP-S score (P<0.0001; ES, 0.50). Adverse events (≥5%) on lurasidone vs. placebo were nausea (15.9% vs. 5.2%), headache (15.1% vs. 13.1%), somnolence (7.9% vs. 3.8%), vomiting (5.2% vs. 3.3%), and weight increase (5.2% vs. 2.3%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.
ConclusionsIn this post-hoc analysis of two placebo-controlled trials, lurasidone demonstrated clinically meaningful improvement of depressive symptoms in youth and young adults with bipolar depression. Lurasidone was generally safe, well-tolerated, and associated with minimal effects on weight, metabolic parameters, and prolactin.
FundingServier Laboratories (Aust.) Pty. Ltd., and Sunovion Pharmaceuticals Inc.
Long-Term Safety and Effectiveness of Lurasidone in Adolescents and Young Adults With Schizophrenia: Pooled Post-hoc Analyses of Two 12-month Extension Studies
- Fabrizio Calisti, Michael Tocco, Yongcai Mao, Andrei Pikalov, Robert Goldman
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- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, pp. 248-249
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Introduction
Earlier onset of schizophrenia, which occurs more commonly in males, is characterized by greater illness severity, chronicity, and functional impairment with a less favorable prognosis than later-onset schizophrenia. The aim of this pooled analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents (13–17 years) and young adults (18–25 years).
MethodsThe 2 pooled studies used similar designs and outcome measures. Patients (13–25 years) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/d), and (80 and 160 mg/d) in the young adult trial. In the open-label long-term trials, adolescent patients were treated with 20-80 mg/d of lurasidone, and adults were treated with 40–160 mg/d of lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S).
ResultsThe safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% discontinued by 12 months due to an adverse event. Mean (SD) change in the PANSS total score from extension Baseline to Months 6 and 12 was -11.8 (13.9) and -15.3 (15.0), respectively (OC); and mean (SD) change in the CGI-S score was -0.8 (1.0) and -1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.
ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone was generally well-tolerated and effective. Long-term treatment was associated with continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin.
FundingAngelini Pharma S.p.A. and Sunovion Pharmaceuticals Inc.
Lurasidone and risk of metabolic syndrome: results from short and long-term studies in patients with bipolar depression
- Michael Tocco, John W. Newcomer, Yongcai Mao, Andrei Pikalov
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- Journal:
- CNS Spectrums / Volume 28 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 24 March 2023, pp. 680-687
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Objective
The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression.
MethodsData used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision).
ResultsThe proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group.
ConclusionsThis post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.
Short-term efficacy and safety of lurasidone versus placebo in antipsychotic-naïve versus previously treated adolescents with an acute exacerbation of schizophrenia
- Christoph U. Correll, Michael Tocco, Jay Hsu, Robert Goldman, Andrei Pikalov
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- Journal:
- European Psychiatry / Volume 65 / Issue 1 / 2022
- Published online by Cambridge University Press:
- 24 March 2022, e23
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Background
To evaluate the efficacy of short-term lurasidone in antipsychotic treatment-naïve (TN) adolescents with schizophrenia versus those treated previously (TP) with antipsychotics.
MethodsPatients aged 13–17 with schizophrenia, and a Positive and Negative Symptom Scale (PANSS) score ≥ 70 and < 120, were randomized to 6 weeks of double-blind treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc, pooled-dose analysis, efficacy was evaluated for TN (criteria: never received antipsychotic treatment) versus TP at the time of the study. Treatment response criteria: ≥20% reduction in PANSS total score.
ResultsAltogether, 57 TN and 269 TP patients enrolled in the 6-week DB study. Mean endpoint change in PANSS total score was significantly greater for lurasidone versus placebo in both the TN group (−25.0 vs. -14.4; p < 0.02; effect size = 0.75), and in the TP group (−17.3 vs. -10.0; p < 0.001; effect size = 0.45); and responder rates were higher for lurasidone versus placebo in both the TN group 84.6% versus 38.9%; number needed to treat [NNT] = 3 and in the TP group (60% vs. 42%; NNT = 6). Rates of treatment-emergent adverse events, and mean changes in body weight and metabolic parameters were similar for the TN and TP groups.
ConclusionsIn a 6-week, placebo-controlled trial, lurasidone demonstrated significant efficacy in adolescents with schizophrenia regardless of previous antipsychotic therapy status; however, the effect size was notably larger in the TN patient group. In both the TN and TP groups, minimal effects were noted on weight, metabolic parameters, or prolactin.
Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study -- CORRIGENDUM
- Christoph U. Correll, Robert L. Findling, Michael Tocco, Andrei Pikalov, Ling Deng, Robert Goldman
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- CNS Spectrums / Volume 27 / Issue 1 / February 2022
- Published online by Cambridge University Press:
- 17 May 2021, p. 129
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Assessing the Benefit-Risk Ratio of Approved Treatments for Bipolar Depression Using Likelihood to be Helped or Harmed (LHH) Analyses
- Leslie Citrome, Michael Tocco, Courtney Zeni, Andrei Pikalov, Robert Goldman
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 146
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Background
Four medications are FDA approved for bipolar depression: lurasidone (LUR), cariprazine (CAR), quetiapine IR & XR (QUE), and olanzapine-fluoxetine combination (OFC). Indirect comparisons for efficacy using Number Needed to Treat (NNT) and for tolerability using Number Needed to Harm (NNH) can be useful clinical benchmarks to aid treatment decisions. Benefit and risk may also be examined using the Likelihood to be Helped or Harmed (LHH). In this post-hoc analysis, we examined the benefit-risk ratio of the four treatments using LHH.
MethodIndividual and pooled monotherapy data from short-term clinical registration trials of patients with bipolar depression were assessed for LUR, CAR, pooled QUE (300 and 600 mg), and pooled OFC (considered as monotherapy for this study at fixed doses of 6/25, 6/50, 12/50 mg) data. NNT estimates were calculated using the proportions of MADRS responders (defined as ≥ 50% improvement at study endpoint) and MADRS remitters (defined as a score of ≤ 10 [for LUR and CAR] and ≤ 12 [for QUE and OFC]) at study endpoint. NNH data were calculated for the proportions of patients who discontinued due to an adverse event (AE) and for individual AEs commonly associated with each treatment. LHH was calculated as the ratio of NNH/NNT to determine the benefit-risk ratio.
ResultsThe NNT estimates for response vs. placebo were: 5 for both LUR 20–60 mg and 80–120 mg; 10 for both CAR 1.5 mg and 3.0 mg; 6 for QUE; and 4 for OFC. The NNTs for remission vs placebo were: 7 for LUR 20–60 mg and 9 for LUR 80–120 mg; 10 for CAR 1.5 mg and 13 for CAR 3.0 mg; 6 for QUE; and 5 for OFC. The NNH estimates for discontinuations due to AEs were: 642 for LUR 20–60 mg and −151 for LUR 80–120 mg; 298 for CAR 1.5 mg and 31 for CAR 3.0 mg; 10 for QUE; and −37 for OFC. NNH values that were negative were assigned a value of 1000 to permit LHH to be calculated. The LHHs for response vs discontinuation due to an AE were: 128.4 for LUR 20–60 mg and 200 for LUR 80–120 mg; 29.8 for CAR 1.5 mg and 3.1 for CAR 3.0 mg; 1.7 for QUE; and 250 for OFC. The LHHs for response vs akathisia were: 3.6 for LUR 20–60 mg and 2.4 for LUR 80–120 mg; 3.6 for CAR 1.5 mg and 1.3 for CAR 3.0 mg; 34 for QUE; and not available (NA) for OFC. The LHHs for response vs EPS were: 8 for LUR 20–60 mg and 3.2 for LUR 80–120 mg; 5 for CAR 1.5 mg and 2.5 for CAR 3.0 mg; NA for QUE; and NA for OFC. The LHH for response vs weight gain was 5.8 for LUR 20–60 mg and 1110 for LUR 80–120 mg; 5 for both doses of CAR; 2.7 for QUE; and 1.5 for OFC.
ConclusionsLHH can illustrate the trade-offs regarding potential benefits versus potential harms. Across a variety of measures, the lower-dose groups for both LUR and CAR generally evidenced a better benefit-risk profile than the higher-dose groups. While quetiapine and OFC demonstrated robust efficacy, their reduced tolerability resulted in a more marginal benefit-risk ratio for some of the outcomes.
FundingSunovion Pharmaceuticals Inc.
Long-Term Effectiveness of Lurasidone in Pediatric Bipolar Depression: Response, Remission and Recovery
- Manpreet Singh, Michael Tocco, Edward Schweizer, Andrei Pikalov
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 148
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Background
Bipolar disorder frequently has an early onset, with an estimated 1.8% prevalence of bipolar I disorder in children and adolescents. Childhood onset of bipolar disorder is typically associated with a chronic, severe, and disabling course of illness. Relatively few prospective studies are available that evaluate the long-term efficacy of atypical antipsychotics in achieving and sustaining response or remission in pediatric patients with bipolar depression. Lurasidone has been approved by the FDA as monotherapy for bipolar depression in pediatric patients ages 10–17 years. The aim of the current post-hoc analysis was to evaluate the long-term efficacy of lurasidone in achieving response or remission in children and adolescents with bipolar depression followed over a two-year period.
MethodPatients 10–17 years with bipolar I depression who completed a 6-week double-blind (DB) study of lurasidone vs. placebo were eligible to enroll in a two-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20–80 mg/d) or switched from placebo to lurasidone. Efficacy measures included the Children’s Depression Rating Scale, Revised (CDRS-R) and the Clinical Global Impression, Bipolar Depression Severity scale (CGI-BP-S). Functioning was evaluated utilizing the Clinician-rated Children’s Global Assessment Scale (CGAS) score, with a score >70 indicating no clinically meaningful functional impairment. Responder criteria were met if a patient achieved criteria = 50% reduction from DB baseline in the CDRS-R total score: remission criteria were met if a patient achieved a CDRS-R Total Score =28 and a YMRS total score =8 and CGI-BP-S depression score =3, and a patient was considered to have met recovery criteria if they achieved remission with a CGAS score >70. In addition, a more stringent outcome, sustained remission, was also analyzed, which required a patient to meet remission criteria for =24 consecutive weeks.
ResultsA total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) patients completed one year of treatment and 168 (54.9%) patients completed two years of treatment. Responder rates at OL baseline, one year, and two years were: 51.0%, 88.4% and 91.1%, respectively; remission rates were 24.3%, 61.3%, and 75.6%, respectively; and recovery rates were 17.7%, 53.8%, and 73.8%. On a Pearson correlation analysis, there was a strong inverse relationship (r = −0.71) between CDRS-R total score, and global functioning as measured by the CGAS. Sustained remission was achieved by 37.2% of patients at one year and 57% of patients after two years.
ConclusionsIn children and adolescents with bipolar depression, up to 2 years of treatment with lurasidone was associated with continued improvement in depressive symptoms, resulting in progressively higher rates of response, remission, recovery, and the more rigorously calculated outcome of sustained remission.
FundingSunovion Pharmaceuticals Inc.
Effect of Lurasidone on Manic Symptoms and Treatment-Emergent Mania in Adult and Pediatric Populations with Bipolar Depression
- Michael Tocco, Andrei Pikalov, Courtney Zeni, Robert Goldman
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, pp. 147-148
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Background
Lurasidone is approved for the treatment of bipolar depression both as monotherapy and adjunctive therapy with lithium or valproate (Li/VPA). The aim of these analyses was to evaluate the prevalence of treatment-emergent mania (TEM) and worsening of mania symptom severity in clinical trials of both adult and pediatric patients with bipolar depression treated with lurasidone.
MethodIn these post-hoc analyses, TEM and change in manic symptom severity as measured by the Young Mania Rating Scale (YMRS) were evaluated in two double-blind (DB), 6-week studies in adults of lurasidone monotherapy, 20–60 mg/d (n=161) and 80–120 mg/d (n=162) vs. placebo (n=162), and adjunctive therapy of lurasidone 20–120 mg/d + Li/VPA (n=179) vs. placebo + Li/VPA (n=161). Prevalence of TEM was also evaluated in a 6-month, open-label (OL) extension study of adults treated with lurasidone monotherapy (n=316) or adjunctive therapy (n=497). In pediatric patients (ages 10–17) TEM and change in manic symptoms was evaluated in a DB 6-week study of lurasidone monotherapy (n=173) vs. placebo (n=170) and in a 24-month OL extension study. TEM was defined as an adverse event of mania or hypomania and/or having a YMRS score =16 at 2 consecutive post-baseline weekly visits (or the final assessment) in short-term studies or 1 post-baseline monthly visit in long-term studies.
ResultsAdult studies: In short-term studies, TEM rates were comparable in patients treated with lurasidone monotherapy 20–60 mg/d (3.7%) and 80–120 mg/d (1.9%) vs. placebo (1.9%). TEM rates were also comparable in patients treated with lurasidone 20–120 mg/d (1.1%) adjunctive to Li/VPA vs. placebo + Li/VPA (1.2%). In the monotherapy study, significant reduction in YMRS score was observed at study endpoint for the 20–60 mg/d group compared to placebo (−1.9 vs. −1.3; p<0.05) with similar improvement relative to placebo in the 80–120 mg/d group. Change for YMRS score was comparable for lurasidone and placebo in the adjunctive study. In long-term studies, 1.3% of adult patients treated with lurasidone monotherapy (n=316) met criteria for mania, and 3.8% of patients on adjunctive lurasidone therapy (n=497) met TEM criteria. Pediatric studies: TEM rates were comparable in patients treated with lurasidone vs. placebo (1.7% vs. 2.3%). LS mean reduction in symptoms of mania from baseline to week 6 was significantly greater for lurasidone vs. placebo on YMRS score (−2.0 vs. −1.1; p<0.05). Pediatric long-term studies: After two years of OL treatment with lurasidone, 5.2% of patients met TEM criteria. Mean change in YMRS total score from DB baseline to Month 24 continued to improve (−2.0).
ConclusionsShort-term and long-term treatment with lurasidone demonstrated significant improvement in manic symptoms and was not associated with an increased risk of TEM in either adult or pediatric patient populations compared to rates reported in clinical populations of patients.
FundingSunovion Pharmaceuticals Inc.
Efficacy of Lurasidone in Antipsychotic-Naive vs. Antipsychotic-Exposed Adolescents with Schizophrenia: Post-Hoc Analysis of a Two-Year, Open-Label Study
- Christoph Correll, Michael Tocco, Andrei Pikalov, Jay Hsu, Robert Goldman
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 147
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Background
Few studies have examined treatment response in adolescents with schizophrenia who are treatment-naive; and there is no placebo-controlled study that we are aware of in first episode treatment-naive patients with schizophrenia. The aim of this analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naive adolescents with schizophrenia.
MethodPatients aged 13–17 years with schizophrenia, and a PANSS total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB) treatment with lurasidone (40 or 80 mg/day) or placebo. Six-week completers were eligible to enroll in a 2-year open-label extension phase receiving lurasidone flexibly dosed from 20–80 mg/day. In a post-hoc analysis, efficacy was evaluated for 2 patient groups based on treatment status prior to entering the initial 6-week DB study (treatment naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment. Efficacy measures included the PANSS total score and the Clinical Global Impression, Severity (CGI-S) score. Level of functioning was assessed using the Children’s Global Assessment Scale (CGAS), with a score of 70 representing normative levels of functioning.
ResultsA total of 50 TN and 221 TP patients completed the 6-week DB study and entered the extension study; and 30 (60.0%) TN and 126 (57.0%) TP patients completed 104 weeks. During the initial 6 weeks of DB treatment, mean change in PANSS total score at endpoint was greater for lurasidone vs. placebo in both the TN group (−25.0 vs. −14.4; P<0.02; effect size, 0.75), and in the TP group (−17.3 vs. −10.0; P<0.001; effect size, 0.45). During OL extension phase treatment with lurasidone, mean change from DB baseline in the PANSS total score for TN and TP patients, at week 52 was −32.6 (n=38) and −28.1 (n=151), respectively; and at week 104 was −33.6 (n=30) and −29.2 (n=126), respectively. Mean change from DB baseline in CGI-S score at both weeks 52 and 104 was −1.8 for TN patients and −1.5 for TP patients. At DB baseline mean CGAS scores indicated significant functional impairment in both the TN and TP patients (CGAS=48 and 43, respectively). During OL treatment with lurasidone, mean change (from DB baseline) in the CGAS score at Weeks 52 and 104, respectively, was +22.0 and +22.9 in TN patients, and +21.1 and +22.9 in TP patients. During OL treatment with lurasidone, mean observed change from DB baseline in the weight (in kg,) at Weeks 52 and 104, respectively, was +4.2 and +4.8 in TN patients, and +4.0 and +5.0 in TP patients. These weight increases are consistent with expected weight gains in adolescents during a 2-year period (based on CDC growth charts).
ConclusionsIn this post-hoc analysis of a 2-year study, adolescents with schizophrenia who had received no previous antipsychotic therapy showed greater improvement compared to previously treated patients during both short- and long-term treatment with lurasidone.
FundingSunovion Pharmaceuticals Inc.
Efficacy and safety of lurasidone in adolescents and young adults with schizophrenia: A pooled post hoc analysis of double-blind, placebo-controlled 6-week studies
- Isabella Costamagna, Fabrizio Calisti, Agnese Cattaneo, Jay Hsu, Michael Tocco, Andrei Pikalov, Robert Goldman
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 10 May 2021, e35
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Background
The aim of this pooled analysis was to evaluate the efficacy and safety of lurasidone in the treatment of an acute exacerbation of schizophrenia in adolescents and young adults.
MethodsThe six pooled studies in this analysis used similar study designs and outcome measures. Patients (aged 13–25 years) were randomized to 6 weeks of double-blind, placebo-controlled treatment with lurasidone in fixed doses of 40, 80, 120, or 160 mg. The primary efficacy endpoint was Week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score; secondary efficacy endpoints included Week 6 change in the Clinical Global Impression–Severity scale.
ResultsThe safety population consisted of 537 patients (mean age: 18.1 years); 82.6% of patients completed the studies. Treatment with lurasidone was significantly better than placebo at all doses (p < 0.001) for change in the PANSS total score at Week 6. Placebo-adjusted PANSS scores ranged from −9.4 to −16.1 (effect sizes: 0.53–0.90), with effect sizes increasing at higher doses. For lurasidone (combined doses), three adverse events occurred with a frequency of ≥5% (nausea: 13.5%; somnolence: 12.1%; akathisia: 10.1%). At last observation carried forward (LOCF)-endpoint weight gain of ≥7% was similar for lurasidone versus placebo (3.6 vs. 4.7%). Minimal median changes were observed at endpoint in cholesterol, −2.0 mg/dL; triglycerides, 0.0 mg/dL; and glucose, 0.0 mg/dL.
ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone in doses of 40–160 mg/d was a safe, well-tolerated, and effective treatment. Short-term treatment with lurasidone was associated with minimal effects on weight and metabolic parameters.
Safety and effectiveness of lurasidone in adolescents with schizophrenia: results of a 2-year, open-label extension study
- Christoph U. Correll, Robert L. Findling, Michael Tocco, Andrei Pikalov, Ling Deng, Robert Goldman
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- Journal:
- CNS Spectrums / Volume 27 / Issue 1 / February 2022
- Published online by Cambridge University Press:
- 20 October 2020, pp. 118-128
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Background
Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia.
MethodsPatients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score.
ResultsAbout 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104.
ConclusionIn adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.
Lurasidone and risk for metabolic syndrome: results from short- and long-term clinical studies in patients with schizophrenia
- Michael Tocco, John W. Newcomer, Yongcai Mao, Andrei Pikalov, Antony Loebel
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- Journal:
- CNS Spectrums / Volume 26 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 14 September 2020, pp. 614-624
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Objective
To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia.
MethodsRates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone.
ResultsMetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 LOCF (adjusted for baseline metabolic syndrome status) was similar for the lurasidone and placebo groups (OR = 1.18; [95% CI, 0.81-1.71]; P = .39), but the odds (vs placebo) were significantly greater for olanzapine (OR = 2.81; [95% CI, 1.53-5.15]; P < .001) and quetiapine (OR = 3.49; [95% CI, 1.93-6.29]; P < .0001). No dose effect was observed for lurasidone across the dose range of 40-160 mg/d. In long-term studies, the odds of MetS after 12 months of treatment was significantly higher for risperidone compared with lurasidone (OR = 2.12; 95% CI, 1.15-3.90; P = .016) and for quetiapine XR compared with lurasidone (OR = 3.92; 95% CI, 1.15-13.40; P = .029). In open-label extension studies, the rate of MetS decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone.
ConclusionIn this analysis of lurasidone clinical trials, the odds of developing metabolic syndrome were minimal during short- and long-term treatment with lurasidone (40-160 mg/d).
168 Effect of Dasotraline on Body Weight in Patients with Binge-Eating Disorder
- Leslie Citrome, Robert Goldman, Joyce Tsai, Ling Deng, Todd Grinnell, Andrei Pikalov
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- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, p. 307
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Background:
Binge-eating disorder (BED) is associated with obesity (BMI ≥30) in approximately 40-45% of patients. Dasotraline is a long-acting dopamine/norepinephrine reuptake inhibitor with a PK profile characterized by slow absorption and an elimination half-life of 47-77 hours, permitting once-daily dosing. In a recent placebo-controlled, flexible-dose study, dasotraline demonstrated significant efficacy in patients with BED. We now report an analysis from this study of the effect of dasotraline on body weight.
Method:Patients with moderate-to-severe BED, based on DSM-5 criteria, were randomized to 12 weeks of double-blind flexible-dose treatment with dasotraline (4-8 mg/d) vs. placebo. The primary efficacy outcome was number of binge-eating days/week. Mean change in body weight at Week 12 (assessed as a safety outcome) was analyzed by baseline body mass index (BMI, kg/m2) category. Inferential statistics were not performed.
Results:The safety population consisted of 317 patients (female, 84%; mean age, 38.2 years; mean weight, 97.3 kg). At baseline, the proportions of patients in each BMI category were as follows: normal (<25 kg/m2: 5.7%), overweight (25 to <30 kg/m2: 18.3%), obesity class I (30 to <35 kg/m2: 24.9%), class II (35 to <40 kg/m2: 29.3%), and class III (≥40 kg/m2: 21.8%). For the overall patient sample, treatment with dasotraline significantly reduced the number of binge-eating days per week vs. placebo (-3.74 vs. -2.75; P<0.0001; effect size = 0.74). Mean changes at Week 12 in weight (kg) for completers treated with dasotraline vs. placebo, by baseline BMI category, were as follows: normal weight (-4.6 vs. -0.2), overweight (-5.8 vs. +1.3), and combined obesity classes I-III (-6.2 vs. +0.3). Among obese patients (Class I-III, combined) treated with dasotraline, weight reduction (≥5%) was observed in 45.3% of patients (vs. 4.1% on placebo); and weight reduction ≥10% in approximately 13.7% of patients (vs. none on placebo). Weight-related adverse events, for dasotraline vs. placebo, consisted of decreased appetite (19.7% vs. 6.9%), decreased weight (12.1% vs. 0%), and increased weight (0.6% vs. 1.3%).
Conclusion:Among patients completing 12 weeks of treatment with dasotraline, weight reduction ≥5% was observed in 45% of obese patients with a BMI ≥30. The most frequent weight-related adverse event was decreased appetite, reported in approximately one in five patients treated with dasotraline.
Clinicaltrials.gov number: NCT02564588
Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.
159 Safety and Efficacy of Lurasidone in Children and Adolescents with Bipolar Depression: Results from a 2-Year Open-label Extension Study
- Melissa P. DelBello, Robert Goldman, Michael Tocco, Ling Deng, Andrei Pikalov
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 301-302
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Background:
Bipolar I disorder frequently has an early onset, with an estimated prevalence rate of 1.8% in pediatric populations. Early onset is associated with a high degree of chronicity; however, limited data are available on the long-term efficacy of drug therapies in pediatric populations. The aim of the current study was to evaluate the long-term safety and efficacy of lurasidone in children and adolescents with bipolar depression.
Method:Patients 10-17 years with bipolar I depression were randomized to 6 weeks of double-blind (DB) treatment with lurasidone or placebo. Patients who completed the study were eligible to enroll in a 2-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20-80 mg/d; LUR-LUR) or switched from placebo to lurasidone (PBO-LUR). The primary efficacy measure was the Children’s Depression Rating Scale, Revised (CDRS-R); response was defined as ≥50% reduction from DB baseline in the CDRS-R total score.
Results:A total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) completed 52 weeks, and 168 (54.9%) completed 104 weeks of treatment. Mean CDRS-R total score at DB baseline was 59.4 in patients treated with lurasidone, and 58.7 in patients treated with placebo; and mean CDRS-R total score at OL baseline (after 6 weeks of DB treatment) was 36.6 in the LUR-LUR group and 41.9 in the PBO-LUR group. For the total sample of patients in the OL study, mean change (from OL baseline) in the CDRS-R score was -13.4 at week 52 and -16.4 at week 104; and responder rates were 51.0% at OL baseline (64.5% for LUR-LUR; 36.9% for PBO-LUR), 88.4% at week 52, and 91.1% at week 104. During OL treatment with lurasidone, 31 patients (10.1%) discontinued due to an adverse event. The most commonly reported events were headache (23.9%), nausea (16.4%), and somnolence (9.8%). OL treatment with lurasidone was associated with few effects on metabolic parameters or prolactin. Mean change from DB baseline in weight was +4.25 kg at week 52 (vs. an expected weight gain of 3.76 kg based on CDC normative data), and +6.75 kg at week 104 (vs. CDC expected weight gain of 6.67 kg).
Conclusion:Two years of treatment with lurasidone in children and adolescents with bipolar depression was generally well-tolerated, with relatively low rates of study discontinuation. Lurasidone treatment was associated with few effects on weight, metabolic parameters, and prolactin. Patients also continued to experience improvement in depressive symptoms during long-term treatment with lurasidone.
Clinicaltrials.gov identifier: NCT01914393
Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.
104 Long-term Efficacy of Lurasidone in Antipsychotic-naïve vs. Antipsychotic-exposed Adolescents with Schizophrenia: Analysis of a Two-Year Study
- Christoph U. Correll, Robert Goldman, Michael Tocco, Jay Hsu, Andrei Pikalov
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- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 267-268
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Background:
Early-onset schizophrenia is characterized by greater severity and more functional impairment than adult-onset schizophrenia. Few studies have prospectively evaluated short- or long-term antipsychotic efficacy in treatment-naïve (vs. previously treated) first-episode schizophrenia. The aim of this post-hoc analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naïve adolescents with schizophrenia.
Method:Patients aged 13-17 years with schizophrenia were randomized to 6 weeks of double-blind (DB), fixed-dose treatment with lurasidone (40 mg/day or 80 mg/day) or placebo. Six-week completers were eligible to enroll in an open-label (OL), flexible dose 2-year lurasidone treatment study. Efficacy over 104 weeks of OL treatment with lurasidone was evaluated for 2 patient groups based on treatment status prior to entering the initial DB study (treatment-naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment prior to randomization. Efficacy measures included the PANSS total score and the Clinical Global Impressions-Severity (CGI-S) score. Treatment response was defined as ≥20% reduction from baseline in PANSS total score.
Results:A total of 50 TN and 221 TP patients completed the 6-week DB study and entered the extension study; and 30 (60.0%) TN and 126 (57.0%) TP patients completed 104 weeks. In the ITT population of the initial DB study, treatment with lurasidone (vs. placebo) yielded larger effects at DB endpoint on the PANSS total score in the TN group (-25.0 vs. -14.4; P<0.02; effect size [ES]=0.75) compared to the TP group (-17.3 vs. -10.0; P<0.001; ES=0.45); and in the CGI-S score in the TN group (-1.07 vs. -0.28; P=0.002; ES=0.97) compared to the TP group (-0.91 vs. -0.55; P=0.005; ES=0.38). During OL treatment with lurasidone, the magnitude of improvement from DB baseline continued to be somewhat larger in the PANSS total score for TN patients (n=38) vs. TP patients (151) at week 52 (-32.6 vs. -28.1) and week 104 (-33.6 vs. -29.2); and in the CGI-S score for TN vs. TP patients at week 52 (-2.1 vs. -1.5) and week 104 (-2.1 vs. -1.6). Responder rates during treatment with lurasidone were 72.0% (TN group) and 61.1% (TP group) at OL baseline (number-needed-to-treat [NNT]=10), 100% and 90.1% at week 52 [NNT=11], and 100% and 88.9% at week 104 [NNT=11]. During OL treatment, the most common adverse events for TN vs. TP patients were headache (26.0% vs. 23.5%), nasopharyngitis (24.0% vs. 5.4%), nausea (16.0% vs. 11.8%), and dizziness (16.0% vs. 4.1%).
Conclusion:In this post-hoc analysis of a 2-year OL extension study, antipsychotic-naïve adolescents with schizophrenia responded well to treatment with lurasidone at doses of 40 mg/day or 80 mg/day. TN patients achieved greater improvement than TP patients during acute treatment; and these greater treatment effects were largely maintained during 2 years of continued treatment with lurasidone.
Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc
169 Dasotraline for Treatment of Adults with Binge-Eating Disorder: Effect on Binge-related Obsessions and Compulsions
- Leslie Citrome, Robert Goldman, Joyce Tsai, Ling Deng, Todd Grinnell, Andrei Pikalov
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- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 307-308
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Background:
Binge-eating disorder (BED), the most common eating disorder in the US, is frequently associated with impairment in quality of life and functioning. Dasotraline, a long-acting dopamine/norepinephrine reuptake inhibitor, has a PK profile characterized by slow absorption and an elimination half-life of 47-77 hours, and is dosed once-daily. In a recent placebo-controlled, flexible-dose study, dasotraline demonstrated significant efficacy in patients with BED. We now report an analysis from this study of the effect of dasotraline on binge-related obsessions and compulsions.
Method:Patients with moderate-to-severe BED, based on DSM-5 criteria, were randomized to 12 weeks of double-blind, placebo controlled, treatment with flexible doses of dasotraline (4, 6, and 8 mg/d). The primary efficacy measure was number of binge-eating days/week; secondary measures included the Binge Eating Clinical Global Impression of Severity (BE-CGI-S) score and the Yale-Brown Obsessive-Compulsive Scale Modified for Binge-Eating (Y-BOCS-BE), a validated, 10-item interviewer-administered measure designed to assess the severity of obsessional thoughts and compulsive behaviors related to binge eating. Change from baseline in efficacy measures in the Intent-to-treat (ITT) population were analyzed using a mixed model for repeated measures (MMRM) analysis.
Results:The ITT population consisted of 317 patients (female, 84%; mean age, 38.2 years). LS mean reduction from baseline in number of Binge Eating (BE) days per week was significantly greater for dasotraline vs. placebo at week 12 (-3.74 vs. -2.75; P<0.0001; effect size [ES] = 0.74; primary endpoint); week 12 change was significantly greater for dasotraline vs. placebo on the Y-BOCS-BE total score (-17.05 vs. -9.88; P<0.0001; ES, 0.96), the obsession subscale score (-8.32 vs. -4.58; P<0.0001; ES, 0.95), and the compulsion subscale score (-8.69 vs. -5.35; P<0.0001; ES, 0.87). All 10 YBOCS-BE items were significantly improved on dasotraline vs. placebo at week 12 (P<0.001 for all comparisons; with effect sizes ranging from 0.54 to 0.90). At Week 12 (LOCF), for dasotraline and placebo, 52.3% and 18.4% of patients, respectively, had a BE-CGI-S score of 1 (“normal; not at all ill”; NNT=3). At endpoint, for patients with a global illness severity score of 1, the corresponding mean Y-BOCS-BE total scores were 0.5 and 0.7 for dasotraline and placebo, respectively, indicating that when BED illness severity approaches “normal, not at all ill”, binge-related obsessions and compulsions demonstrate comparably low levels of severity.
Conclusion:In this placebo-controlled, 12-week study of patients with moderate-to-severe binge eating disorder, treatment with dasotraline (4-8 mg/d) was associated with significant and clinically meaningful reduction in binge-related obsessional thoughts and compulsive behaviors.
Clinicaltrials.gov number: NCT02564588
Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.
160 Lurasidone and Metabolic Syndrome: Results from Short- and Long-Term Clinical Studies in Patients with Bipolar Depression
- Michael Tocco, John W. Newcomer, Yongcai Mao, Andrei Pikalov
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- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 302-303
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Background:
Among patients with depressive disorders, the prevalence of metabolic syndrome (MetS) is estimated to range from 35-40% and has been associated with increased mortality rates. The aim of this post-hoc analysis was to assess the effect of treatment with lurasidone on the prevalence of MetS in patients with bipolar depression.
Method:Lurasidone data (dose range, 20-120 mg/d) used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (total N=1,192), consisting of 1 monotherapy, and 2 adjunctive therapy trials with lithium or valproate. Patients who completed the short-term trials continued into a 6-month open-label (OL) extension study, with 6-month (LOCF-endpoint) data available on 274 patients treated with lurasidone monotherapy, and 436 patients treated with lurasidone adjunctive therapy. Also analyzed was a recurrence prevention study in stabilized bipolar patients who completed up to 20 weeks of OL adjunctive treatment with lurasidone, and then were randomized to 28 weeks of DB adjunctive therapy with lurasidone or placebo (N=497). MetS was defined based on NCEP ATP III criteria (2005 revision).
Results:In the short-term monotherapy and adjunctive therapy studies, the proportion of patients at baseline meeting NCEP III criteria for MetS were 27.6% and 23.6%, respectively, for lurasidone, and 23.8% and 25.1%, respectively, for placebo; and at week 6 (LOCF) the proportion with MetS was 27.5% and 26.6%, respectively, for lurasidone and 29.9% and 20.2%, respectively, for placebo. The proportion of patients who did not meet MetS criteria at baseline but developed MetS at week 6 (LOCF) was similar for lurasidone vs. placebo in the monotherapy study (9.9% vs. 11.6%); and in the two adjunctive therapy studies (10.3% vs. 8.3%). During the 6-month OL extension study, the proportion of patients treated with lurasidone monotherapy and adjunctive therapy who did not meet MetS criteria at OL baseline but developed MetS at month 6 (LOCF) was 11.7% and 11.9%, respectively. Conversely, the proportion of patients who met MetS criteria at OL baseline, but no longer met criteria at month 6 (LOCF) was 9.5% and 7.7%, respectively. In the 20-week, OL phase of the recurrence prevention study, the proportion of patients treated with adjunctive lurasidone who did not meet MetS criteria at OL baseline but developed MetS at endpoint was 11.5% (LOCF). After up to 28 weeks of DB treatment, the proportion of patients who did not meet MetS criteria at DB baseline but developed MetS at endpoint was 9.0% in the adjunctive lurasidone group, and 10.5% in the adjunctive placebo group (LOCF).
Conclusion:This post-hoc analysis found that short- and long-term treatment with lurasidone was associated with a relatively low risk for the development of metabolic syndrome in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.
Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.
108 Lurasidone in Children and Adolescents With Bipolar Depression Presenting With Mixed Features
- Cynthia Siu, Andrei Pikalov, Michael Tocco, Antony Loebel
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- Journal:
- CNS Spectrums / Volume 23 / Issue 1 / February 2018
- Published online by Cambridge University Press:
- 15 June 2018, p. 70
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Objective
To evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed features.
MethodsPatients 10 to 17 years of age, inclusive, with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with once-daily, flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed features (subthreshold hypomanic symptoms) was defined as a YMRS score > 5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome), and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures (MMRM) analysis.
ResultsAt baseline, mixed features were present in 54.2% of patients (lurasidone, n=97/173; placebo, n=89/170). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in CDRS-R scores at week 6 in the mixed features group (-21.5 vs -15.9; P<0.01; effect size, 0.45), and in the group without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Likewise, lurasidone was associated with greater effect size (vs placebo) for reductions inCGI-BP-S scores at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features(lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%).
ConclusionsIn this post-hoc analysis, lurasidone was found to be efficacious for treating child and adolescent patients with bipolar depression presenting with mixed features(assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.
Funding AcknowledgementsSunovion Pharmaceuticals Inc.
Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study
- Joyce Tsai, Michael E. Thase, Yongcai Mao, Daisy Ng-Mak, Andrei Pikalov, Antony Loebel
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- CNS Spectrums / Volume 22 / Issue 2 / April 2017
- Published online by Cambridge University Press:
- 30 March 2017, pp. 236-245
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Objective
The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.
MethodsThe data in this analysis were derived from a study of patients meeting the DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM–A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM–A≤14) and moderate-to-severe anxiety (HAM–A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.
ResultsTreatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (–18.4 vs. –12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (–22.0 vs. –13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM–A total score for patients with both mild anxiety (–7.6 vs. –4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (–11.4 vs. –6.1, p<0.0001, ES=0.91).
ConclusionsIn this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.