Many patients with obstructive sleep apnea (OSA) experience residual excessive sleepiness (ES), even with continuous positive airway pressure (CPAP) treatment. Depression is commonly comorbid with OSA. How depression affects the treatment and measurement of patients’ ES is unknown. This study evaluated armodafinil, a non-amphetamine, wakefulness-promoting medication, in patients with ES associated with OSA who have a comorbid depressive disorder.
This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled patients with residual ES associated with CPAP-treated OSA, as well as a Major Depressive Disorder (MDD) or Dysthymic Disorder requiring antidepressant monotherapy. Inclusion criteria included a Clinical Global Impressions of Severity (CGI-S) score of moderately ill or worse (for ES), Epworth Sleepiness Scale (ESS) score of ≥ 10, and 17-Item Hamilton Rating Scale for Depression (HAM-D-17) score of < 17. Efficacy outcomes included the mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT), Clinical Global Impressions of Change (CGI-C), ESS, Functional Outcomes of Sleep Questionnaire (FOSQ) score, and Brief Fatigue Inventory (BFI) score. A blinded, baseline summary was conducted, per protocol, when 50% of the planned sample completed the study. Enrollment is complete, and final efficacy and tolerability data will be presented.
Of 134 patients, 92% were diagnosed with MDD and 8% with Dysthymic Disorder; 53% were moderately ill and 34% markedly ill (CGI-S). At baseline, mean(SD) ESS score was 14.7(3.2); MSL was 20.5(8.4) minutes and HAM-D-17 score was 6.7(4.3), indicating remitted depression. Mean FOSQ score was 14.4(2.9), and mean worst fatigue score BFI was 6.7(2.0), indicating functional impairment and moderate fatigue, respectively. The effects of armodafinil on wakefulness and overall clinical condition compared with placebo will be reported, along with secondary and tolerability outcomes.
Patients with residual ES associated with CPAP-treated OSA who have a comorbid depressive disorder report fatigue and functional impairment.
This is the first large-scale study of armodafinil in patients with residual ES associated with OSA who have a comorbid depressive disorder.
Andrew Krystal, Grant monies (from industry related sources) Dr. Andrew Krystal: Astellas Pharma Inc., Cephalon, Inc., Evotec Inc., GlaxoSmithKline, Merck & Co., Inc., National Institute of Health, Neurocrine Biosciences, Inc., Neurogen Corporation, Neuronetics Inc., Pfizer Inc., Respironics Inc., sanofi-aventis, Sepracor Inc., Somaxon Pharmaceuticals, Inc., Takeda Pharmaceuticals North America, Inc., and Transcept Pharmaceuticals, Inc. Dr. Alan Lankford: Actelion, Arena, Cephalon, Evotec, GlaxoSmithKline; Lilly, Merck, Neurim, Neurocrine, Neurogen, Organon, Pfizer, Respironics, Sanofi-Aventis, Somaxon, Takeda, Transcept, and Vanda.; Employee Dr. Ronhua Yang received personal compensation from Cephalon, Inc. as an employee. Dr. Yang holds stock options in Cephalon, Inc. Dr. Gregory Rippon received personal compensation from Cephalon, Inc. as an employee. Dr. Rippon holds stock options in Cephalon, Inc.; Consultant fee, speaker bureau, advisory committee, etc. Dr. Andrew Krystal: Actelion Pharmaceuticals Ltd, Arena Pharmaceuticals, Inc., Astellas Pharma Inc., Axiom Pharmaceuticals, Inc., AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Company, Cephalon, Inc., Eli Lilly and Company, GlaxoSmithKline, Jazz Pharmaceuticals, Inc., Johnson & Johnson Pharmaceutical Research & Development, L.L.C., King Pharmaceuticals, Inc., Merck & Co., Inc., Neurocrine Biosciences, Inc., Neurogen Corporation, Novartis Pharmaceuticals Corporation, Organon Pharmaceuticals USA, Inc., Pfizer Inc., Research Triangle Institute, Respironics Inc., Roche Labs, sanofi-aventis, Sepracor Inc., Sleep Medicine Education Institute, Somaxon Pharmaceuticals, Inc., Takeda Pharmaceuticals North America, Inc., and Transcept Pharmaceuticals, Inc.Dr. Alan Lankford: Actelion, Cephalon, Concert, GlaxoSmithKline; Jazz, Neurocrine, Neurogen, Ovation, Pfizer, Somaxon, and Transcept.; No Product/Research Disclosure Information