THERAPEUTICS

Brands

• Provigil
• Alertec
• Modiodal
• see index for additional brand names

Generic?

• No

Class

• Wake-promoting

Commonly Prescribed For

• (bold for FDA approved)
• Reducing excessive sleepiness in patients with narcolepsy and shift work sleep disorder
• Reducing excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) (adjunct to standard treatment for underlying airway obstruction)
• Attention deficit hyperactivity disorder (ADHD)
• Fatigue and sleepiness in depression
• Fatigue in multiple sclerosis

How The Drug Works

• Unknown, but clearly different from classical stimulants such as methylphenidate and amphetamine
• Binds to and requires the presence of the dopamine transporter; also requires the presence of alpha adrenergic receptors
• Hypothetically acts as an inhibitor of the dopamine transporter
• Increases neuronal activity selectively in the hypothalamus
• Presumably enhances activity in hypothalamic wakefulness center (TMN, tuberomammillary nucleus) within the hypothalamic sleep wake switch by an unknown mechanism
• Activates tuberomammillary nucleus neurons that release histamine
• Activates other hypothalamic neurons that release orexin/hypocretin

How Long Until It Works

• Can immediately reduce daytime sleepiness and improve cognitive task performance within 2 hours of first dosing
• Can take several days to optimize dosing and clinical improvement

If It Works

• Improves daytime sleepiness and may improve attention as well as fatigue
• Does not prevent one from falling asleep when needed
• May not completely normalize wakefulness
• Treat until improvement stabilizes and then continue treatment indefinitely as long as improvement persists

If It Doesn’t Work

• Change dose; some patients do better with an increased dose but some actually do better with a decreased dose
• Augment or consider an alternative treatment for daytime sleepiness, fatigue, or ADHD

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Modafinil is itself an adjunct to standard treatments for obstructive sleep apnea/hypopnea syndrome (OSAHS); if continuous positive airway pressure (CPAP) is the treatment of choice, a maximal effort to treat first with CPAP should be made prior to initiating modafinil and CPAP should be continued after initiation of modafinil
• Modafinil is itself an augmenting therapy to antidepressants for residual sleepiness and fatigue in major depressive disorder
• Best to attempt another monotherapy prior to augmenting with other drugs in the treatment of sleepiness associated with sleep disorders or problems concentrating in ADHD
• Combination of modafinil with stimulants such as methylphenidate or amphetamine or with atomoxetine for ADHD has not been systematically studied
• However, such combinations may be useful options for experts, with close monitoring, when numerous monotherapies for sleepiness or ADHD have failed

Tests

• None for healthy individuals