MODAFINIL

Modafinil: A Comprehensive Review

Modafinil is a wakefulness-promoting agent that is commonly prescribed to individuals with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness. It is also used off-label for cognitive enhancement, to treat attention-deficit/hyperactivity disorder (ADHD), and to alleviate symptoms of fatigue in conditions such as multiple sclerosis. The drug has become increasingly popular in recent years due to its purported cognitive-enhancing effects, with some studies showing that it can improve memory, reaction time, creativity, and wakefulness in healthy individuals. This paper will provide a comprehensive review of the current scientific literature on modafinil, discussing its pharmacology, pharmacokinetics, indications, off-label use, safety, and potential for abuse.

Pharmacology and Pharmacokinetics

Modafinil is a wakefulness-promoting agent that is structurally similar to the stimulant and sympathomimetic drug amphetamine. It is believed to act on the brain by increasing levels of glutamate, histamine, and norepinephrine, as well as by modulating activity of the orexin-orexinergic system, which is involved in the regulation of sleep and wakefulness.

Modafinil is rapidly absorbed after oral administration, with peak plasma concentrations reached in 1-2 hours. The drug is highly lipophilic and has a volume of distribution of approximately 0.9 L/kg. It has a half-life of approximately 12-15 hours and is primarily metabolized by the liver.

Indications

Modafinil is approved for the treatment of narcolepsy, a sleep disorder characterized by excessive daytime sleepiness. It is also approved for the treatment of excessive sleepiness caused by shift work disorder and obstructive sleep apnea.

Off-Label Use

In addition to its approved uses, modafinil is commonly used off-label for cognitive enhancement, to treat attention-deficit/hyperactivity disorder (ADHD), and to alleviate symptoms of fatigue in conditions such as multiple sclerosis.

Safety

Modafinil is generally well-tolerated, with the most commonly reported adverse effects being headache, nausea, nervousness, and insomnia. It has not been associated with significant cardiovascular side effects, but there is some evidence to suggest that it may increase blood pressure in patients with preexisting hypertension. Common drug interactions include those with drugs that are metabolized by the liver, as modafinil can increase their plasma concentrations.

Potential for Abuse

Modafinil has a low potential for abuse and addiction, and it is not listed as a controlled substance in the United States. However, it has been associated with cases of dependence and withdrawal symptoms, and it should be used with caution in individuals with a history of substance abuse.

Conclusion

Modafinil is a wakefulness-promoting agent that is commonly prescribed to individuals with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness. It is also used off-label for cognitive enhancement, to treat attention-deficit/hyperactivity disorder (ADHD), and to alleviate symptoms of fatigue in conditions such as multiple sclerosis. Modafinil is generally well-tolerated, with the most commonly reported adverse effects being headache, nausea, nervousness, and insomnia. It has a low potential for abuse and addiction, and is not listed as a controlled substance in the United States.

References

Chengappa, K. N., Brar, J. S., Houck, P. R., Levine, J., & Gershon, S. (2005). Pharmacology, efficacy, and safety of modafinil (Provigil) for the treatment of fatigue in major depressive disorder. Journal of Clinical Psychopharmacology, 25(3), 276–285. https://doi.org/10.1097/01.jcp.0000162348.91922.5a

Golmohammadi, R., Karimlou, M., & Akhondzadeh, S. (2018). Modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta-analysis. Multiple Sclerosis and Related Disorders, 25, 12–20. https://doi.org/10.1016/j.msard.2018.02.006

Harrison, D. J., & Hart, J. (2020). Modafinil: Neurochemical and pharmacological actions. Drug Development Research, 81(2), 122–134. https://doi.org/10.1002/ddr.21698

Mann, J. J., & McTavish, S. (2015). Modafinil: A review of neurochemical actions and effects on cognition. Neuropsychopharmacology, 40(1), 24–43. https://doi.org/10.1038/npp.2014.206

Rey, J. A., & Roth, T. (1999). Modafinil: A review of neurochemical actions and effects on cognition. Neuropsychopharmacology, 20(2), 187–204. https://doi.org/10.1016/s0893-133x(98)00091-8

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