TY - JOUR
T1 - Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression
T2 - A meta-analysis of randomized controlled trials
AU - Nunez, Nicolas A.
AU - Singh, Balwinder
AU - Romo-Nava, Francisco
AU - Joseph, Boney
AU - Veldic, Marin
AU - Cuellar-Barboza, Alfredo
AU - Cabello Arreola, Alejandra
AU - Vande Voort, Jennifer L.
AU - Croarkin, Paul
AU - Moore, Katherine M.
AU - Biernacka, Joanna
AU - McElroy, Susan L.
AU - Frye, Mark A.
N1 - Funding Information:
We are grateful to MrLarry Prokop, MLS from Mayo Clinic Library, Mayo Clinic Rochester, MN, USA for helping with the literature search.
Funding Information:
Dr Frye reports Grant Support from Assurex Health, Mayo Foundation, Medibio. Consultant (Mayo)—Actify Neurotherapies, Allergan, Intra‐Cellular Therapies, Inc, Janssen, Myriad, Neuralstem Inc,Takeda, Teva Pharmaceuticals. He reports CME/Travel/Honoraria from the American Physician Institute, CME Outfitters, Global Academy for Medical Education. Dr McElroy has been a consultant to or member of the scientific advisory boards of Allergan, Avanir, Bracket, F. Hoffmann‐La Roche Ltd., Mitsubishi Tanabe Pharma America, Myriad, Opiant, Shire, and Sunovion. She has been a principal or co‐investigator on studies sponsored by Allergan, Avanir, Azevan, Brainsway, Marriott Foundation, Medibio, Myriad, Neurocrine, Novo Nordisk, Shire, and Sunovion. She is also an inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent's assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr Romo‐Nava reports support from the Brain & Behavior Research Foundation NARSAD Young Investigator Award; receiving nonfinancial support from Soterix Medical outside the submitted work; and having patent 62 581 968 pending. Dr Singh had received research time support from Medibio. It is unrelated to the current study. Other authors have none to declare. All the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Objective: The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods: A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP-I) or bipolar II (BP-II) depression. Data for response/remission and all-cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results: Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP-I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I2 = 34%, P =.19; I2 = 18%, P =.30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01-1.37; P =.03) and remission (RR, 1.38; 95% CI, 1.10-1.73; P =.005). All-cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89-1.30; P =.45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39-2.5; P =.98; RR, 1.02; 95% CI, 0.37-2.85; P =.97). Conclusion: This narrower scope meta-analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic-enhancing agents are encouraged.
AB - Objective: The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods: A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP-I) or bipolar II (BP-II) depression. Data for response/remission and all-cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results: Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP-I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I2 = 34%, P =.19; I2 = 18%, P =.30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01-1.37; P =.03) and remission (RR, 1.38; 95% CI, 1.10-1.73; P =.005). All-cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89-1.30; P =.45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39-2.5; P =.98; RR, 1.02; 95% CI, 0.37-2.85; P =.97). Conclusion: This narrower scope meta-analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic-enhancing agents are encouraged.
KW - armodafinil
KW - augmentation strategy
KW - bipolar depression
KW - meta-analysis
KW - modafinil
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U2 - 10.1111/bdi.12859
DO - 10.1111/bdi.12859
M3 - Review article
C2 - 31643130
AN - SCOPUS:85077885090
SN - 1398-5647
VL - 22
SP - 109
EP - 120
JO - Bipolar disorders
JF - Bipolar disorders
IS - 2
ER -