Modafinil in the treatment of excessive sleepiness

Figures & data

Table 1 Demographic characteristics and illness severity ratings at baseline for patients in large-scale, double-blind, placebo-controlled studies of modafinil

	Obstructive sleep apnea studies n = 446a	Shift work disorder studies n = 455a	Narcolepsy studies n = 530a
Mean (SD) age, yr	49.7 (9.4)	39.5 (9.2)	41.8 (13.3)
Gender, n (%)
Male	340 (76)	243 (53)	239 (45)
Female	106 (24)	212 (47)	291 (55)
Race, n (%)
White	396 (89)	321 (71)	434 (82)
Black	29 (7)	99 (22)	77 (15)
Other	21 (4)	34 (7)	19 (4)
CGI-S rating
Not recorded	43 (10)	0 (0)	0 (0)
Normal, mildly, or slightly ill	121 (27)	0 (0)	91 (17)
Moderately ill	199 (45)	280 (62)	237 (45)
Markedly, severely, or extremely ill	83 (19)	175 (38)	202 (38)

a Patients receiving one dose of study medication (modafinil or placebo) who had at least one post-baseline follow-up. Adapted from Schwartz 2005.

Abbreviations: SD, standard deviation; CGI-S, clinical global impression of severity.

Table 2 Summary outcomes for patients receiving modafinil or placebo in the OSA studies

Study/Reference	Measure	Treatment	Mean at baseline	Mean at final visit	Mean (SD) change from baseline to final visit	P-valuea
4-week study/Pack et al 2001	MSLT sleep latency (min)	Modafinil 400 mg	7.4	8.6		<0.05
		Placebo	7.5	7.2
	ESS score	Modafinil 400 mg	14.2	9.6		<0.001
		Placebo	14.4	12.4
4-week study/Dinges and Weaver 2003	PVT number of lapses (msec)	Modafinil 400 mg			−0.814 (0.426)	0.112
		Placebo			0.346 (.550)
	PVT number of lapses transformed (msec)	Modafinil 400 mg			−0.532 (0.177b)	0.01
		Placebo			0.118 (0.171b)
	PVT median reaction time (msec)	Modafinil 400 mg			−10.343 (4.424b)	0.01
		Placebo			4.936 (4.777b)
12-week study/Black and Hirshkowitz 2005	MWT sleep latency (min)	Modafinil 200 mg			1.6	<0.0001c
		Modafinil 400 mg			1.5
		Placebo			−1.1
	ESS score	Modafinil 200 mg			−4.5	<0.0001c
		Modafinil 400 mg			−4.5
		Placebo			−1.8
	FOSQ total score	Modafinil 200 mg			1.92 (2.47)	0.001d
		Modafinil 400 mg			2.13 (2.61)
		Placebo			0.84 (1.89)
	FOSQ vigilance	Modafinil 200 mg			0.48 (0.67)	0.0007d
		Modafinil 400 mg			0.55 (0.59)
		Placebo			0.25 (0.54)
	FOSQ general productivity	Modafinil 200 mg			0.30 (0.45)	0.0006d
		Modafinil 400 mg			0.33 (0.49)
		Placebo			0.08 (0.40)
	FOSQ activity	Modafinil 200 mg			0.41 (0.59)	0.02d
		Modafinil 400 mg			0.45 (0.65)
		Placebo			0.20 (0.49)

a For the change from baseline for modafinil versus placebo.

b SEM.

c For overall and pairwise comparisons of modafinil with placebo.

d For overall comparisons of modafinil with placebo.

Abbreviations: SD, standard deviation; OSA, obstructive sleep apnea; MSLT, Multiple Sleep Latency Test; ESS, Epworth Sleepiness Scale; PVT, Psychomotor Vigilance Task; MWT, Maintenance of Wakefulness Test; FOSQ, Functional Outcomes of Sleep Questionnaire.

Table 3 Summary outcomes for patients receiving modafinil or placebo in the SWD studies

Study/Reference	Measure	Treatment	Mean (SD) at baseline	Mean (SD) at final visit	Mean (SD) change from baseline to final visit	P-valuea
12-week study #1/Czeisler et al 2005	MSLT sleep latency (min)	Modafinil 200 mg	2.07 (0.2)	3.77 (0.5)	1.7 (0.4)	0.002
		Placebo	2.04 (0.2)	2.37 (0.3)	0.3 (0.3)
	KSS score	Modafinil 200 mg	7.3 (0.1)	5.8 (0.2)	−1.5 (0.2)	<0.001
		Placebo	7.1 (0.1)	6.7 (0.2)	−0.4 (0.2)
	PVT number of lapses	Modafinil 200 mg	12.50b	10.25b	−2.6c	<0.001
		Placebo	16.13b	23.75b	3.8c
12-week study #2/Erman et al 2007	FOSQ total scored	Modafinil 300 mg			2.3	<0.05
		Placebo			1.6
	FOSQ vigilance	Modafinil 300 mg			0.6	<0.05
		Placebo			0.4
	FOSQ activity	Modafinil 200 mg			0.5	<0.05
		Placebo			0.3
		Modafinil 300 mg			0.5	<0.01
		Placebo			0.3
	FOSQ productivity	Modafinil 300 mg			0.4	<0.01
		Placebo			0.3
	SF-36 mental component scoree	Modafinil 200 mg			3.7	<0.05
		Modafinil 300 mg			3.2	<0.05
		Placebo			0.7
	SF-36 vitality	Modafinil 200 mg			15.0	<0.001
		Modafinil 300 mg			14.8	<0.0001
		Placebo			5.3
	SF-36 role emotional	Modafinil 300 mg			4.3	<0.05
		Placebo			−2.9

a For the change from baseline for modafinil versus placebo.

b Median number of lapses.

c Median change from baseline.

d FOSQ total scores at baseline were similar for modafinil 200 mg, modafinil 300 mg, and placebo (range: 14.3–14.7 points).

e SF-36 mental component scores at baseline were similar for the 3 groups (range: 45.3–47.4).

Abbreviations: SD, standard deviation; SWD, shift work disorder; MSLT, Multiple Sleep Latency Test; PVT, Psychomotor Vigilance Task; KSS, Karolinska Sleepiness Score; FOSQ, Functional Outcomes of Sleep Questionnaire; SF-36, 36-item Short Form Health Survey.

Table 4 Summary outcomes for patients receiving modafinil or placebo in the narcolepsy studies

Study/Reference	Measure	Treatment	Mean (SD) at baseline	Mean (SD) at final visit	Mean (SD) change from baseline to final visit	P-valuea
9-week study #1/US Modafinil in Narcolepsy Multicenter Study Group 1998	MSLT sleep latency (min)	Modafinil 200 mg	2.9 (2.5)	4.7 (4.4)		<0.001
		Modafinil 400 mg	3.3 (2.9)	5.2 (4.5)		<0.001
		Placebo	2.8 (2.2)	3.3 (3.2)
	MWT sleep latency (min)	Modafinil 200 mg	5.8 (5.0)	8.1 (6.1)		<0.001
		Modafinil 400 mg	6.6 (5.2)	8.9 (6.2)		<0.001
		Placebo	5.8 (4.7)	5.1 (4.7)
	ESS score	Modafinil 200 mg	17.9 (3.8)	14.4 (5.7)		<0.001
		Modafinil 400 mg	17.1 (4.2)	13.0 (5.7)		<0.001
		Placebo	18.3 (3.3)	17.1 (5.0)
9-week study #2/US Modafinil in Narcolepsy Multicenter Study Group 2000	MSLT sleep latency (min)	Modafinil 200 mg	3.0 (2.2)	4.9 (4.3)		<0.001
		Modafinil 400 mg	2.7 (2.0)	5.1 (4.0)
		Placebo	2.2 (1.8)	3.5 (3.4)
	MWT sleep latency (min)	Modafinil 200 mg	6.1 (4.9)	8.2 (5.9)		0.001
		Modafinil 400 mg	5.9 (4.4)	7.8 (5.3)		<0.001
		Placebo	6.0 (5.0)	5.5 (4.5)
	ESS score	Modafinil 200 mg	17.4 (3.8)	13.0 (5.1)		<0.001
		Modafinil 400 mg	18.0 (3.4)	12.3 (5.1)		<0.001
		Placebo	17.6 (4.0)	15.8 (4.8)
9-week studies combined/Beusterien et al 1999	SF-36 vitality	Modafinil 200 mg			11	<0.05
		Modafinil 400 mg			13	<0.05
		Placebo			3
	SF-36 role limitations-	Modafinil 200 mg			6
	emotional	Modafinil 400 mg			10	<0.05
		Placebo			–1
	SF-36 role limitations-	Modafinil 200 mg			14	<0.05
	physical	Modafinil 400 mg			20	<0.05
		Placebo			6
	SF-36 social function	Modafinil 200 mg			6
		Modafinil 400 mg			11	<0.05
		Placebo			2

a For the change from baseline for modafinil versus placebo.

Abbreviations: SD, standard deviation; MSLT, Multiple Sleep Latency Test; MWT, Maintenance of Wakefulness Test; ESS, Epworth Sleepiness Scale.

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