From the Guidelines
Modafinil should not be recommended to manage symptoms of cancer-related fatigue in adults with advanced cancer or at the end of life, as stated in the 2024 ASCO-Society for Integrative Oncology guideline update 1.
Overview of Modafinil
Modafinil is a prescription medication primarily used to treat excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work sleep disorder. The typical dosage ranges from 100-200mg taken once daily in the morning for narcolepsy and sleep apnea, or about one hour before starting a work shift for shift work disorder.
Mechanism of Action and Side Effects
Modafinil works by affecting certain brain chemicals that control the sleep/wake cycle, though its exact mechanism isn't fully understood. It's not recommended for people with certain heart conditions, liver problems, or a history of drug abuse. Common side effects include headache, nausea, nervousness, and insomnia.
Use in Cancer-Related Fatigue
Despite some earlier studies suggesting potential benefits of modafinil in managing cancer-related fatigue, such as the 2010 study published in the Journal of the National Comprehensive Cancer Network 1, the most recent and highest quality evidence from the 2024 ASCO-Society for Integrative Oncology guideline update 1 indicates that modafinil should not be recommended for this purpose due to limited effectiveness and potential risks.
Key Points to Consider
- The 2024 guideline update provides a conditional recommendation against the use of wakefulness agents like modafinil for cancer-related fatigue in adults with advanced cancer or at the end of life 1.
- Earlier studies, such as those published in 2010 1, may have suggested benefits, but the most recent evidence supersedes these findings.
- Modafinil's use should be carefully considered, especially in patients with certain medical conditions or those taking other medications.
From the FDA Drug Label
Modafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD). Modafinil tablets are a prescription medicine used to improve wakefulness in adults who are very sleepy due to one of the following diagnosed sleep disorders: narcolepsy, obstructive sleep apnea (OSA), shift work disorder (SWD).
Indications for Modafinil:
- Narcolepsy: Modafinil is used to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy.
- Obstructive Sleep Apnea (OSA): Modafinil is used to treat excessive sleepiness, but not the obstruction or medical condition that is causing OSA.
- Shift Work Disorder (SWD): Modafinil is used to improve wakefulness in adults with excessive sleepiness associated with SWD.
Modafinil tablets may help the sleepiness caused by these conditions, but it may not stop all sleepiness. Modafinil tablets do not take the place of getting enough sleep. 2 2
From the Research
Overview of Modafinil
- Modafinil is a wake-promoting agent that is pharmacologically distinct from CNS stimulants, such as amfetamine, dexamfetamine, and methylphenidate 3.
- It is approved for use in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome (OSA/HS), or shift work sleep disorder (SWSD) 3, 4.
Mechanism of Action and Pharmacokinetics
- The mechanism of action of modafinil has not been clearly established, but it may indirectly increase wakefulness through inhibition of cortical γ-aminobutyric acid (GABA) release via serotonergic mechanisms 5.
- Modafinil is extensively biotransformed in the liver to the inactive metabolites modafinil acid and modafinil sulphone, before being eliminated primarily in the urine (elimination half-life 9 to 14 hours) 5.
Efficacy and Tolerability
- Modafinil is effective in promoting wakefulness in patients with OSA/HS, SWSD, and narcolepsy, and is generally well tolerated 3, 5, 4.
- It improves objectively determined sleep latency, overall clinical condition related to severity of sleepiness, and reduces patient-reported sleepiness 4.
- Modafinil has a low abuse potential and does not suppress cataplexy in patients with narcolepsy 5.
Clinical Uses
- Modafinil is recommended for use as an adjunct to standard therapies that treat the underlying airway obstruction in OSA 4.
- It is also used to treat excessive sleepiness associated with SWD and narcolepsy 3, 5, 4.
- Armodafinil, a related compound, has also been shown to be effective and well tolerated in patients with excessive sleepiness associated with treated OSA, SWD, or narcolepsy 6.