Armodafinil in the treatment of sleep/wake disorders

Figures & data

Table 1 Identification and initial assessment of ES in the clinic

Recognizing ES in the clinic
Presenting profiles alerting a high degree of suspicion for ES Diagnosed sleep/wake disorder Cardiovascular disease, particularly obese patients, with or without an underlying sleep/wake disorder Generalized somatic symptoms with or without an underlying sleep/wake disorder Employer referral for ES High-risk professions, eg, shift workers or professional drivers Polypharmacy (prescription and/or OTC), particularly with drugs that affect the central nervous system such as antidepressants, neuroleptics, beta-blockers, analgesics
Clinical goals
Exclude or establish comorbidity with an underlying medical disorder, eg anemia, diabetes, neurodegenerative condition Exclude or establish comorbidity with a psychiatric disorder, particularly mood and anxiety disorders Identify any underlying sleep/wake disorder if undiagnosed Identify ES component
Screening and assessment of ES
Screening Direct questioning	Assessment Epworth sleepiness scale Multiple sleep latency test Maintenance of wakefulness test
Initial treatment of ES
Address any underlying medical disorder Address underlying sleep/wake disorder	Improve sleep hygiene Prescribe wakefulness-promoting agent

Abbreviations: ES, excessive sleepiness; OTC, over the counter

Table 2 The Epworth Sleepiness Scale¹⁶

Responses:

0 = would never doze

1 = slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Situation	Chance of dozing (complete using responses above)
Sitting and reading	_______________
Watching TV	_______________
Sitting inactive in a public place such as a meeting	_______________
As a passenger in a car for an hour without a break	_______________
Lying down to rest in the afternoon when circumstances permit	_______________
Sitting and talking with someone	_______________
Sitting quietly after a lunch without alcohol	_______________
In a car, while stopped for a few minutes in traffic	_______________
Total score

©1991 by the American Academy of Sleep Medicine. Reproduced with permission of the American Academy of Sleep Medicine.

Figure 1 Chemical structure of armodafinil.

Figure 2 Improvements in maintenance of wakefulness with armodafinil versus placebo among adults with residual ES during effective management of OSA.³⁹ Panel A: early assessments (09:00 to 15:00). Panel B: late assessments (15:00 to 19:00).

Notes: *P < 0.001 vs placebo; **P < 0.05 vs placebo.
Abbreviations: ES, excessive sleepiness; MWT, maintenance of wakefulness test; OSA, obstructive sleep apnea; SEM, standard error of the mean.

Table 3 Efficacy of armodafinil in the treatment of ES associated with OSA, SWD, and narcolepsy

Study	Treatment	Wakefulness	Fatigue (Brief Fatigue Inventory)	Cognition (Cognitive Drug Research Computerized Assessment Battery)	Patient-reported wakefulness
OSA
Roth et al^Citation36 (n = 395)	Armodafinil (150/250 mg) Placebo	MWT:  +1.9 mins  −1.7 mins (P < 0.001)	Pooled analysis:^Citation38  Armodafinil 150 mg: −1.2  Armodafinil 250 mg: −1.3  Placebo: −0.6 (P < 0.01 vs armodafinil combined)	Pooled analysis:^Citation39 Episodic secondary memory, final visit change from baseline:  Armodafinil combined: 10.2 U  Placebo: −0.7 U (P < 0.01 vs armodafinil combined) No significant differences for speed of memory, power of attention, or continuity of attention	ESS Pooled analysis:^Citation39 Significant improvement with armodafinil combined vs placebo from week 4 (P < 0.0001)
Hirshkowitz et al^Citation37 (n = 259)	Armodafinil (150/250 mg) Placebo	MWT:  +2.3 mins  −1.3 mins (P = 0.0003)			Response rate (ESS < 10 points):  Armodafinil: 49%  Placebo: 26%
SWD
Roth et al^Citation40 Czeisler et al^Citation41 (n = 216)	Armodafinil 150 mg Placebo (Given 30–60 minutes before the shift)	MSLT:  +3.1 mins  +0.4 mins (P < 0.0001)	Not reported	Significant improvement in the quality of episodic secondary memory and power and continuity of attention	Karolinska Sleepiness Scale: significant improvement with armodafinil vs placebo from week 4 (P < 0.005)
Narcolepsy
Harsh et al^Citation42 (n = 194)	Armodafinil (150/250 mg) Placebo	MWT:  0900–1500: +1.9 mins  1500–1900: +1.6 mins  0900–1500: −1.9 mins (P < 0.01 vs armodafinil combined)  1500–1900: −1.2 mins (P < 0.05 vs armodafinil combined)	Mean change from baseline:  Armodafinil 150 mg: −1.5  Armodafinil 250 mg: −1.3  Placebo: −0.3 (P < 0.0002 vs armodafinil combined)	Significant improvement for armodafinil vs placebo from baseline in:  Power of attention (P < 0.005)  Quality of episodic secondary memory (P < 0.05)  Speed of memory (P < 0.05)	ESS Mean change from baseline:  Armodafinil 150 mg: −4.1 (P = 0.0044 vs placebo)  Armodafinil 250 mg: −3.8 (P = 0.0015 vs placebo)
	Placebo				Response rate (ESS < 10 points):  Armodafinil 150 mg: 21% (P = 0.0312 vs placebo)  Armodafinil 250 mg: 28% (P = 0.0023 vs placebo)  Placebo: 7%

Abbreviations: ES, excessive sleepiness; ESS, Epworth Sleepiness Scale; MSLT, Multiple Sleep Latency Test; MWT, Maintenance of Wakefulness Test; OSA, obstructive sleep apnea; SWD, shift-work disorder.

Figure 3 Improvements in MWT with armodafinil versus placebo among adults with narcolepsy. Reproduced with permission from Harsh JR, Haydak R, Rosenberg R, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006;22(4):761–774.⁴² Copyright © 2006 Informa Healthcare.

Abbreviations: MWT, maintenance of wakefulness test; SEM, standard error of the mean.

Table 4 The most commonly reported adverse events (>5% of patients) among adults with narcolepsy or OSA treated with armodafinil (150 mg or 250 mg daily)^39,42

Patient population	Adverse event	Incidence (%)
		Armodafinil (150/250 mg)	Placebo
OSA	Headache	17	8
Armodafinil (n = 391)	Nausea	6	4
Placebo (n = 260)	Insomnia	6	3
	Dizziness	5	2
	Anxiety	5	<1
Narcolepsy	Headache	22	11
Armodafinil (n = 131)	Nausea	10	0
Placebo (n = 63)	Dizziness	5	0

Abbreviations: OSA, obstructive sleep apnea; SWD, shift-work disorder.

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