TY - JOUR
T1 - Randomized, placebo-controlled, adjunctive study of armodafinil for bipolar I depression
T2 - implications of novel drug design and heterogeneity of concurrent bipolar maintenance treatments
AU - Frye, Mark A.
AU - Amchin, Jess
AU - Bauer, Michael
AU - Adler, Caleb
AU - Yang, Ronghua
AU - Ketter, Terence A.
N1 - Funding Information:
This study was sponsored by the Teva Pharmaceutical Industries, Ltd. (Petah Tikva, Israel).
Funding Information:
TAK has received research funding from the Agency for Healthcare Research and Quality, AstraZeneca, Eli Lilly, Pfizer, Sepracor, Sunovion, and Teva Pharmaceuticals (formerly Cephalon), served as an advisor/consultant to Allergan, Avanir, Forest, Janssen, Merck, Sepracor, Sunovion, Quintiles, and Teva Pharmaceuticals (formerly Cephalon), and served as a speaker and received honoraria from Abbott, AstraZeneca, GlaxoSmithKline, Janssen, Johnson & Johnson, and Otsuka. TAK’s spouse, Nzeera Ketter, MD, is employed by Janssen, Johnson & Johnson and has stock ownership/options with Janssen, Johnson & Johnson.
Funding Information:
Medical writing assistance was provided by John H. Simmons, MD, of Peloton Advantage and was funded by the Teva Branded Pharmaceutical Products R & D, Inc. (Frazer, PA). Teva provided a full review of the article.
Funding Information:
CA has received research funding from Merck and Forest and served as a speaker and received honoraria from Sunovion. He has received grant support from the National Institute of Mental Health and non-profit foundations.
Funding Information:
MAF has received grant support from Assurex, Janssen Research & Development, Mayo Foundation, Myriad, the National Institute of Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), and Pfizer, served as a Consultant for (Mayo)-Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad, Sunovion, Supernus Pharmaceuticals, and Teva Pharmaceuticals. Mayo Clinic has a financial interest in Assurex Health; this technology is not referenced in this publication/presentation.
Funding Information:
MB has received grants from the American Foundation for Suicide Prevention, Bundesministeriums für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), the European Commission, the National Alliance for Research on Schizophrenia and Depression (NARSAD), and Stanley Medical Research Institute and received honoraria as a board member, speakers bureau member, or consultant for AstraZeneca, Ferrer International, Janssen, Lilly, Lundbeck, Otsuka, Pfizer, GSK, Servier, and Takeda.
Publisher Copyright:
© 2015, Frye et al.
PY - 2015/12/7
Y1 - 2015/12/7
N2 - Background: Some, but not all, prior investigations suggest armodafinil may have utility as an adjunctive treatment in bipolar I depression. Methods: Multicenter, randomized, double-blind study in patients aged 18 to 65 years experiencing a depressive episode despite maintenance therapy for bipolar I disorder. Patients were randomized to receive adjunctive armodafinil 150 mg/day or adjunctive placebo for 8 weeks. Primary efficacy outcome was change from baseline in 30-Item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) total score at week 8. Safety and tolerability were monitored. Results: Of 656 patients screened, 399 were randomized, of whom 308 (77 %) were taking a protocol-allowed mood stabilizer as monotherapy. The primary efficacy outcome did not reach statistical significance; however, several secondary efficacy outcomes demonstrated statistically significant advantages for adjunctive armodafinil (n = 197) over adjunctive placebo (n = 196), including Clinical Global Impression of Severity of Illness for depression (weeks 6, 8, and endpoint; all P < 0.05), Global Assessment of Functioning (weeks 4, 8, and endpoint; all P < 0.02), IDS-C30 remitter rates (week 8 and endpoint; both P < 0.02), and mean change from baseline in IDS-C30 total score at week 7 (P < 0.05). Adjunctive armodafinil and adjunctive placebo were generally well tolerated. Although adjunctive armodafinil compared with adjunctive placebo yielded a higher headache rate (15 vs 8 %), it yielded similar (generally favorably low) rates of all-cause discontinuation (16 vs 16 %), adverse event discontinuation (4 vs 5 %), nausea (6 vs 4 %), ≥7 % weight gain (2 vs 5 %), anxiety (4 vs 3 %), insomnia (3 vs 2 %), sedation/somnolence (1 vs 1 %), and hypomania (0 vs <1 %). Conclusions: In this study, adjunctive armodafinil compared with adjunctive placebo in bipolar I depression did not separate in the primary efficacy outcome but demonstrated advantages for several secondary efficacy outcomes and was generally well tolerated. Additional research is warranted and necessary to better identify clinical predictors (e.g., atypical depressive symptoms, specific anti-manic/mood-stabilizing agents used) that would provide optimized, individualized therapeutics for bipolar depression. Trial registration: ClinicalTrials.gov: NCT01305408
AB - Background: Some, but not all, prior investigations suggest armodafinil may have utility as an adjunctive treatment in bipolar I depression. Methods: Multicenter, randomized, double-blind study in patients aged 18 to 65 years experiencing a depressive episode despite maintenance therapy for bipolar I disorder. Patients were randomized to receive adjunctive armodafinil 150 mg/day or adjunctive placebo for 8 weeks. Primary efficacy outcome was change from baseline in 30-Item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) total score at week 8. Safety and tolerability were monitored. Results: Of 656 patients screened, 399 were randomized, of whom 308 (77 %) were taking a protocol-allowed mood stabilizer as monotherapy. The primary efficacy outcome did not reach statistical significance; however, several secondary efficacy outcomes demonstrated statistically significant advantages for adjunctive armodafinil (n = 197) over adjunctive placebo (n = 196), including Clinical Global Impression of Severity of Illness for depression (weeks 6, 8, and endpoint; all P < 0.05), Global Assessment of Functioning (weeks 4, 8, and endpoint; all P < 0.02), IDS-C30 remitter rates (week 8 and endpoint; both P < 0.02), and mean change from baseline in IDS-C30 total score at week 7 (P < 0.05). Adjunctive armodafinil and adjunctive placebo were generally well tolerated. Although adjunctive armodafinil compared with adjunctive placebo yielded a higher headache rate (15 vs 8 %), it yielded similar (generally favorably low) rates of all-cause discontinuation (16 vs 16 %), adverse event discontinuation (4 vs 5 %), nausea (6 vs 4 %), ≥7 % weight gain (2 vs 5 %), anxiety (4 vs 3 %), insomnia (3 vs 2 %), sedation/somnolence (1 vs 1 %), and hypomania (0 vs <1 %). Conclusions: In this study, adjunctive armodafinil compared with adjunctive placebo in bipolar I depression did not separate in the primary efficacy outcome but demonstrated advantages for several secondary efficacy outcomes and was generally well tolerated. Additional research is warranted and necessary to better identify clinical predictors (e.g., atypical depressive symptoms, specific anti-manic/mood-stabilizing agents used) that would provide optimized, individualized therapeutics for bipolar depression. Trial registration: ClinicalTrials.gov: NCT01305408
KW - Armodafinil
KW - Bipolar I disorder
KW - Major depressive episode
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U2 - 10.1186/s40345-015-0034-0
DO - 10.1186/s40345-015-0034-0
M3 - Article
AN - SCOPUS:85041672973
VL - 3
JO - International Journal of Bipolar Disorders
JF - International Journal of Bipolar Disorders
SN - 2194-7511
IS - 1
M1 - 18
ER -