Modafinil is an oral prescription medication that improves wakefulness in people with narcolepsy and shift work sleep disorder. It also enhances alertness in patients with obstructive sleep apnea in addition to treating the underlying obstruction.
Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness, cataplexy (sudden loss of muscle tone), sleep paralysis, and hallucinations. Managing narcolepsy often requires a combination of lifestyle changes, behavioral strategies, and pharmacotherapy. Medications play a crucial role in managing symptoms and improving the quality of life for individuals with narcolepsy.
Medications for Narcolepsy
While no cure is available for narcolepsy, current medication, and non-pharmacologic therapy approaches can improve QOL and reduce symptoms such as excessive daytime sleepiness (EDS), cataplexy, disturbed nocturnal sleep, and hypnagogic/hypnopompic hallucinations. Non-pharmacologic treatment emphasizes regular, sufficient nocturnal sleep and strategic timing of daytime naps to promote wakefulness.
Medications that increase the release or inhibit the reuptake of norepinephrine and dopamine have wake-promoting effects, whereas drugs that affect adrenergic receptors have stimulant-like effects. Modalert 200mg also has a number of other mechanisms that contribute to its effects on central neurotransmitter systems.
Among these are its affinity for dopamine transporters in the brainstem and prefrontal cortex, its inhibition of serotonin reuptake at all brain levels, its influence on the release of histamine, and its modulation of g-aminobutyric acid B receptors in the hypothalamus. In addition, studies using dual-probe microdialysis have shown that Modafinil 200 amplifies the increase of extracellular cortical serotonin induced by the antidepressants fluoxetine and imipramine in the awake rat.
Medications for Shift Work Sleep Disorder
If lifestyle measures do not alleviate your symptoms, a doctor may prescribe medications to keep you awake during work shifts and help you fall asleep when you are ready to sleep. These medicines can include anti narcoleptics, such as methylphenidate (Ritalin), and sleep-promoting medications, such as melatonin, eszopiclone (Lunesta), or zolpidem (Ambien). Antidepressants or antianxiety medications might also be used to promote sleepiness, as these drugs often reduce anxiety and depression.
Modafinil causes a dose-dependent decrease in GABA in the cortex, medial preoptic area and posterior hypothalamus, striatum, and globus pallidus, and at higher doses in the hippocampus, substantia nigra, and nucleus accumbens. It has also been shown to reduce power in the a-2 and b-1-3 bands of the resting EEG, measured with low-resolution brain electromagnetic tomography, in the cingulate and dorsolateral prefrontal cortex.
A double-blind placebo-controlled fMRI study of modafinil 200 mg after overnight sleep deprivation found that it improved performance on a working memory task, the WCST. In addition, a 3-week regimen of 400 mg/day modafinil remedied the decline in a-2 and b-1-3 EEG power in the dorsolateral prefrontal cortex and anterior cingulate cortex in a narcolepsy population with a 4-day treatment compared to placebo (Schwartz et al, 2004).
Medications for Obstructive Sleep Apnea
Modafinil is the drug of choice for narcolepsy, with worldwide clinical experience indicating that it is more effective than other stimulants in controlling diurnal excessive sleepiness. It also has a better side-effect profile, especially compared to amphetamine, and is not associated with the abuse potential that is associated with methylphenidate.
A 7-day course of parenteral modafinil results in dose-dependent decreases of cortical a-2 and b-2 power in resting EEG, reversing the decrements that are seen with placebo treatment (Tanganelli et al 1994). In addition to its effects on arousal and activity through catecholamine systems, modafinil has been shown to cause a reduction in GABA in ascending dosages from the cortex to the medial preoptic area/posterior hypothalamus, globus pallidus, hippocampus, and substantia nigra (Ferraro et al 1998).
Modafinil has also been demonstrated to improve cognitive performance, including working memory, episodic memory, and processes that require cognitive control, in humans and animal models. This may be related to its reversal of the decline in frontal cortex activity associated with narcolepsy.
Medications for Fatigue
Modafinil (2-[(diphenylmethyl) sulfinyl] acetamide; brand name Provigil in the US and Nuvigil in the rest of the world) is a wake-promoting agent first developed and marketed in the early 1990s for the excessive sleepiness associated with narcolepsy. It is structurally unrelated to amphetamine but has demonstrated different effects on physiology and behavior in animal and human models, suggesting a distinct mechanism of action. The arousal and activity-promoting effects of modafinil are mediated by adrenergic (particularly a and b) receptors, with relatively little effect on the monoamine system or nerve membrane ion channels.
Modafinil is well tolerated and has been shown to improve cognitive performance in narcolepsy patients. It also has been studied in healthy subjects subjected to simulated night shifts and sleep deprivation and has been found to improve performance on the Wisconsin Card Sort Test and the Stroop test, compared to placebo or 600 mg caffeine. Long-term use of stimulants is not recommended, since they can worsen fatigue.
