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Efficacy and Safety of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Results of a 6 Month Open-label Study
2015 AAGP Annual Meeting (2) which aspects of our CSI are most generative of academic progress. We created record keeping for scholars’ progress and faculty’s interventions to track measurable outcomes (e.g. grants, awards, papers, presentations). We will review academic life post-residency for these trainees to elucidate effectiveness of the CSI long-term, and will also compare the current group of trainee participants with past trainees who did not engage with such an Institute. Results: Program evaluation data are being collected and will be reported. Conclusions: Dissemination of the concept of such an Institute is vital to the academic life of psychiatrists, and has implications for patient care. Academic psychiatry has evolved into a field increasingly divided between research-driven concepts and their clinical applications. However, a majority of researched findings have arisen from astute clinical observations, and research products emerging from one area of expertise often have unintended broad utility. The shift in function of the Montreal Cognitive Assessment from early Alzheimer’s assessment to a screening tool for cognitive deficits in multiple conditions offers a classic example from geriatrics. A CSI creates an infrastructure for these developments and a community generative of academic progress. It offers a model for an innovative educational program with demonstrated efficacy in fostering scholarship in the Weill Cornell Department of Psychiatry. Clinical scholarship maintains the health of the field and its academic institutions, particularly as the current cost-driven climate threatens to undermine academic identity, idea sharing and career-oriented self-examination.
Poster Number: NR 25
Efficacy and Safety of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Results of a 6 Month Open-label Study
Brent Forester, MD, MSc1,2; Martha Sajatovic, MD3; Joyce Tsai, PhD4; Hans Kroger, MPH, MS4; Andrei Pikalov, MD, PhD4; Josephine Cucchiaro, PhD4; Antony Loebel, MD4 1
Harvard Medical School, Boston, MA McLean Hospital, Belmont, MA 3 Case Western Reserve University School of Medicine, Cleveland, OH 4 Sunovion Pharmaceuticals, Inc, Marlborough, MA and Fort Lee, NJ, MA 2
Introduction: Long-term treatment of bipolar disorder in the elderly has not been well-studied. This secondary analysis evaluated the safety and efficacy of 6 months of treatment with lurasidone in patients over 55 years with bipolar depression. Methods: Older adult patients (age 55 years) who completed one of three 6 week, double-blind, placebo-controlled trials of lurasidone were enrolled in a 6 month, open-label, extension study. One acute study evaluated monotherapy with lurasidone; two acute studies evaluated treatment with lurasidone adjunctive to lithium or valproate. Patients who met DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score 20 entered the acute double-blind studies. All patients who completed 6 weeks of double-blind treatment, and who consented to participate in the extension study, started open-label treatment with lurasidone on a dose of 60 mg for one week, regardless of double-blind treatment assignment. After one week, dosing was flexible at 20-120 mg/day. Long-term effects of lurasidone on weight and metabolic parameters were evaluated from double-blind acute study baseline to 6 month endpoint, based on a last observation carried forward (LOCF) analysis. Treatment-emergent adverse events were analyzed from double-blind acute study baseline in patients who were randomized to acute treatment with lurasidone, and who continued to receive lurasidone in the extension study. Change in MADRS and the Clinical Global Impressions Bipolar Version, Severity of Illness scale (CGI-BP-S) were analyzed descriptively, from double-blind baseline to 6 month endpoint (LOCF). Results: The proportion of older adults who entered the extension study (safety sample) was 55/316 (17.4%) on lurasidone monotherapy (mean age, 60.2; mean double-blind baseline MADRS, 29.7; CGI-BP-S, 4.6), and 86/497 (17.3%) on lurasidone adjunctive therapy (mean age, 59.9; mean double-blind baseline MADRS, 30.0; CGI-BP-S, 4.6). At the end of 6 months of openlabel treatment with lurasidone, monotherapy and adjunctive therapy, respectively, minimal changes were observed in mean weight (-1.0 kg; -0.4 kg); and median total cholesterol (-2.0 mg/dL; +6.0 md/dL), triglycerides (+2.5 mg/dL; +6.0 mg/dL), and HbA1c (0.0%; -0.1%). Treatment-emergent adverse events (10%) reported among patients receiving continued monotherapy with lurasidone were: fatigue (18.4%), insomnia (18.4%), headache (15.8%), somnolence (15.8%), dizziness (13.2%), nasopharyngitis (13.2%), nausea (13.2%), depression (10.5%), and dry mouth (10.5%); and among patients receiving continued adjunctive therapy with lurasidone were: akathisia (31.7%), insomnia (22.0%), tremor (19.5%), nausea (12.2%), somnolence (12.2%). Mean change in the MADRS was -15.7 for the monotherapy group, and -17.8 for the adjunctive therapy group. Mean change in the CGI-BP-S was -2.0 for the monotherapy group, and -2.2 for the adjunctive therapy group.
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Am J Geriatr Psychiatry 23:3, Supplement 1
2015 AAGP Annual Meeting Conclusions: Results of these secondary analyses suggest that 6 months of treatment with lurasidone, as monotherapy, or adjunctive to lithium or valproate, was safe and efficacious in older adults with bipolar depression. Minimal changes were observed in weight and metabolic parameters. The antidepressant efficacy of lurasidone was maintained over the 6 month treatment period. NCT00868959. This research was funded by: Sponsored by Sunovion Pharmaceuticals Inc.
Poster Number: NR 26
Efficacy and Safety of Lurasidone in Older Adults with Bipolar Depression: Analysis of Two Double-blind, Placebo-controlled Studies
Martha Sajatovic, MD1; Brent Forester, MD, MSc2,3; Joyce Tsai, PhD4; Hans Kroger, MPH, MS4; Andrei Pikalov, MD, PhD4; Josephine Cucchiaro, PhD, PhD4; Antony Loebel, MD4 1
Case Western Reserve University School of Medicine, Cleveland, OH Harvard Medical School, Boston, MA 3 McLean Hospital, Belmont, MA 4 Sunovion Pharmaceuticals, Inc, Marlborough, MA and Fort Lee, NJ, NJ 2
Introduction: The treatment of bipolar disorder in the elderly has not been well-studied. This secondary analysis evaluated the efficacy of lurasidone in two randomized trials of patients aged 55 years and older with bipolar depression. Methods: Patients meeting DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score 20 were randomized to 6 weeks of once-daily, double-blind treatment with lurasidone 20-60 mg/day or 80-120 mg/day, or placebo in a monotherapy study; or lurasidone 20-120 mg/day or placebo in a adjunctive therapy study with either lithium or valproate. The primary endpoint was LS mean change from baseline to Week 6 in the MADRS total score for both studies based on a mixed model for repeated measures (MMRM) analysis. The criterion for response was 50% reduction in MADRS score at last observation carried forward (LOCF) endpoint analyzed by logistic regression. Results: The proportion of older adults was 83/485 (17.1%) in the monotherapy study, and 53/340 (15.6%) in the adjunctive therapy study. At Week 6 in the monotherapy study, mean change among older adults in the MADRS was significantly greater for the lurasidone 20-60 mg (-15.4; P<0.01; effect size¼0.86) and 80-120 mg groups (-14.1; P<0.02; effect size¼0.74) vs placebo (-7.1); and mean Week 6 change in the CGI-BP-S was significantly greater among older adults for the lurasidone 2060 mg (-1.7; P<0.05; effect size¼0.73) and 80-120 mg groups (-1.6; P<0.05; effect size¼0.65) vs placebo (-0.8). Responder rates among older adults were significantly higher for lurasidone 20-60 mg (53.8%; P<0.01; NNT¼3) compared with placebo (14.8%), and trended higher in the 80-120 mg group (40.0%; P¼0.054; NNT¼4). At Week 6 in the adjunctive therapy study, mean change among older adults was numerically greater for lurasidone vs placebo on the MADRS (-13.9 vs -11.1; ns; effect size¼0.26), and the CGI-BP-S score (-1.4 vs -0.9; ns; effect size¼0.43); responder rates were numerically greater for lurasidone vs placebo (46.2% vs 37.0%; ns; NNT¼11). Among older adults in the monotherapy study, discontinuation due to adverse events occurred in 7.7% of patients on lurasidone 20-60 mg, 6.7% on lurasidone 80-120 mg, and 3.7% on placebo; and adverse events with an incidence 5% (and >2-times the rate on placebo) on lurasidone 20-60 mg, 80-120 mg, and placebo, respectively, were akathisia (0%, 9.7% vs. 3.6%), anxiety (7.4%, 0% vs. 0%), diarrhea (7.4%, 6.5% vs. 3.6%), insomnia (7.4%, 9.7% vs. 3.6%), nasopharyngitis (7.4%, 3.2% vs. 0%), pruritus (7.4%, 0% vs. 0%), restlessness (0%, 6.5% vs. 0%), somnolence (11.1%, 3.2% vs. 3.6%), and vomiting (7.4%, 3.2% vs. 3.6%). Among older adults in the adjunctive therapy study, discontinuation due to adverse events occurred in 3.8% of patients on lurasidone, and 7.4% on placebo; and adverse events with an incidence 5% (and >2-times the rate on placebo) were akathisia (19.2% vs. 0%), abnormal dreams (7.7% vs 3.7%), and insomnia (11.5% vs. 0%). Conclusions: These secondary analyses suggest lurasidone monotherapy has significantly greater efficacy than placebo in the treatment of older adults with bipolar depression. Compared with placebo, lurasidone adjunctive to lithium or valproate was associated with numerically better response that did not reach statistical significance. Lurasidone was well-tolerated in the shortterm treatment of older adults with bipolar depression. The most common adverse events in this older population were akathisia, insomnia, and somnolence. NCT00868699, NCT00868452. This research was funded by: Sponsored by Sunovion Pharmaceuticals Inc.
Am J Geriatr Psychiatry 23:3, Supplement 1
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Poster Number: NR 25
Efficacy and Safety of Long-term Treatment with Lurasidone in Older Adults with Bipolar Depression: Results of a 6 Month Open-label Study
Brent Forester, MD, MSc1,2; Martha Sajatovic, MD3; Joyce Tsai, PhD4; Hans Kroger, MPH, MS4; Andrei Pikalov, MD, PhD4; Josephine Cucchiaro, PhD4; Antony Loebel, MD4 1
Harvard Medical School, Boston, MA McLean Hospital, Belmont, MA 3 Case Western Reserve University School of Medicine, Cleveland, OH 4 Sunovion Pharmaceuticals, Inc, Marlborough, MA and Fort Lee, NJ, MA 2
Introduction: Long-term treatment of bipolar disorder in the elderly has not been well-studied. This secondary analysis evaluated the safety and efficacy of 6 months of treatment with lurasidone in patients over 55 years with bipolar depression. Methods: Older adult patients (age 55 years) who completed one of three 6 week, double-blind, placebo-controlled trials of lurasidone were enrolled in a 6 month, open-label, extension study. One acute study evaluated monotherapy with lurasidone; two acute studies evaluated treatment with lurasidone adjunctive to lithium or valproate. Patients who met DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score 20 entered the acute double-blind studies. All patients who completed 6 weeks of double-blind treatment, and who consented to participate in the extension study, started open-label treatment with lurasidone on a dose of 60 mg for one week, regardless of double-blind treatment assignment. After one week, dosing was flexible at 20-120 mg/day. Long-term effects of lurasidone on weight and metabolic parameters were evaluated from double-blind acute study baseline to 6 month endpoint, based on a last observation carried forward (LOCF) analysis. Treatment-emergent adverse events were analyzed from double-blind acute study baseline in patients who were randomized to acute treatment with lurasidone, and who continued to receive lurasidone in the extension study. Change in MADRS and the Clinical Global Impressions Bipolar Version, Severity of Illness scale (CGI-BP-S) were analyzed descriptively, from double-blind baseline to 6 month endpoint (LOCF). Results: The proportion of older adults who entered the extension study (safety sample) was 55/316 (17.4%) on lurasidone monotherapy (mean age, 60.2; mean double-blind baseline MADRS, 29.7; CGI-BP-S, 4.6), and 86/497 (17.3%) on lurasidone adjunctive therapy (mean age, 59.9; mean double-blind baseline MADRS, 30.0; CGI-BP-S, 4.6). At the end of 6 months of openlabel treatment with lurasidone, monotherapy and adjunctive therapy, respectively, minimal changes were observed in mean weight (-1.0 kg; -0.4 kg); and median total cholesterol (-2.0 mg/dL; +6.0 md/dL), triglycerides (+2.5 mg/dL; +6.0 mg/dL), and HbA1c (0.0%; -0.1%). Treatment-emergent adverse events (10%) reported among patients receiving continued monotherapy with lurasidone were: fatigue (18.4%), insomnia (18.4%), headache (15.8%), somnolence (15.8%), dizziness (13.2%), nasopharyngitis (13.2%), nausea (13.2%), depression (10.5%), and dry mouth (10.5%); and among patients receiving continued adjunctive therapy with lurasidone were: akathisia (31.7%), insomnia (22.0%), tremor (19.5%), nausea (12.2%), somnolence (12.2%). Mean change in the MADRS was -15.7 for the monotherapy group, and -17.8 for the adjunctive therapy group. Mean change in the CGI-BP-S was -2.0 for the monotherapy group, and -2.2 for the adjunctive therapy group.
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Am J Geriatr Psychiatry 23:3, Supplement 1
2015 AAGP Annual Meeting Conclusions: Results of these secondary analyses suggest that 6 months of treatment with lurasidone, as monotherapy, or adjunctive to lithium or valproate, was safe and efficacious in older adults with bipolar depression. Minimal changes were observed in weight and metabolic parameters. The antidepressant efficacy of lurasidone was maintained over the 6 month treatment period. NCT00868959. This research was funded by: Sponsored by Sunovion Pharmaceuticals Inc.
Poster Number: NR 26
Efficacy and Safety of Lurasidone in Older Adults with Bipolar Depression: Analysis of Two Double-blind, Placebo-controlled Studies
Martha Sajatovic, MD1; Brent Forester, MD, MSc2,3; Joyce Tsai, PhD4; Hans Kroger, MPH, MS4; Andrei Pikalov, MD, PhD4; Josephine Cucchiaro, PhD, PhD4; Antony Loebel, MD4 1
Case Western Reserve University School of Medicine, Cleveland, OH Harvard Medical School, Boston, MA 3 McLean Hospital, Belmont, MA 4 Sunovion Pharmaceuticals, Inc, Marlborough, MA and Fort Lee, NJ, NJ 2
Introduction: The treatment of bipolar disorder in the elderly has not been well-studied. This secondary analysis evaluated the efficacy of lurasidone in two randomized trials of patients aged 55 years and older with bipolar depression. Methods: Patients meeting DSM-IV-TR criteria for bipolar I depression, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score 20 were randomized to 6 weeks of once-daily, double-blind treatment with lurasidone 20-60 mg/day or 80-120 mg/day, or placebo in a monotherapy study; or lurasidone 20-120 mg/day or placebo in a adjunctive therapy study with either lithium or valproate. The primary endpoint was LS mean change from baseline to Week 6 in the MADRS total score for both studies based on a mixed model for repeated measures (MMRM) analysis. The criterion for response was 50% reduction in MADRS score at last observation carried forward (LOCF) endpoint analyzed by logistic regression. Results: The proportion of older adults was 83/485 (17.1%) in the monotherapy study, and 53/340 (15.6%) in the adjunctive therapy study. At Week 6 in the monotherapy study, mean change among older adults in the MADRS was significantly greater for the lurasidone 20-60 mg (-15.4; P<0.01; effect size¼0.86) and 80-120 mg groups (-14.1; P<0.02; effect size¼0.74) vs placebo (-7.1); and mean Week 6 change in the CGI-BP-S was significantly greater among older adults for the lurasidone 2060 mg (-1.7; P<0.05; effect size¼0.73) and 80-120 mg groups (-1.6; P<0.05; effect size¼0.65) vs placebo (-0.8). Responder rates among older adults were significantly higher for lurasidone 20-60 mg (53.8%; P<0.01; NNT¼3) compared with placebo (14.8%), and trended higher in the 80-120 mg group (40.0%; P¼0.054; NNT¼4). At Week 6 in the adjunctive therapy study, mean change among older adults was numerically greater for lurasidone vs placebo on the MADRS (-13.9 vs -11.1; ns; effect size¼0.26), and the CGI-BP-S score (-1.4 vs -0.9; ns; effect size¼0.43); responder rates were numerically greater for lurasidone vs placebo (46.2% vs 37.0%; ns; NNT¼11). Among older adults in the monotherapy study, discontinuation due to adverse events occurred in 7.7% of patients on lurasidone 20-60 mg, 6.7% on lurasidone 80-120 mg, and 3.7% on placebo; and adverse events with an incidence 5% (and >2-times the rate on placebo) on lurasidone 20-60 mg, 80-120 mg, and placebo, respectively, were akathisia (0%, 9.7% vs. 3.6%), anxiety (7.4%, 0% vs. 0%), diarrhea (7.4%, 6.5% vs. 3.6%), insomnia (7.4%, 9.7% vs. 3.6%), nasopharyngitis (7.4%, 3.2% vs. 0%), pruritus (7.4%, 0% vs. 0%), restlessness (0%, 6.5% vs. 0%), somnolence (11.1%, 3.2% vs. 3.6%), and vomiting (7.4%, 3.2% vs. 3.6%). Among older adults in the adjunctive therapy study, discontinuation due to adverse events occurred in 3.8% of patients on lurasidone, and 7.4% on placebo; and adverse events with an incidence 5% (and >2-times the rate on placebo) were akathisia (19.2% vs. 0%), abnormal dreams (7.7% vs 3.7%), and insomnia (11.5% vs. 0%). Conclusions: These secondary analyses suggest lurasidone monotherapy has significantly greater efficacy than placebo in the treatment of older adults with bipolar depression. Compared with placebo, lurasidone adjunctive to lithium or valproate was associated with numerically better response that did not reach statistical significance. Lurasidone was well-tolerated in the shortterm treatment of older adults with bipolar depression. The most common adverse events in this older population were akathisia, insomnia, and somnolence. NCT00868699, NCT00868452. This research was funded by: Sponsored by Sunovion Pharmaceuticals Inc.
Am J Geriatr Psychiatry 23:3, Supplement 1
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