Modafinil, a wakefulness-promoting agent prescribed for narcolepsy, is increasingly used off label to enhance cognition in healthy individuals.
As modafinil promotes wakefulness, it may seem surprising that some users experience excessive fatigue and drowsiness while taking the drug.
However, while modafinil is considered to be relatively safe and well-tolerated, this is not always the case. Some individuals have experienced extreme fatigue while taking modafinil, with some to the point where they are unable to work.
While some of these adverse effects usually are due to misuse of the medication, other cases appear to have been related to drug interactions.
Cases of severe fatigue with modafinil use
One case report documented a 30-year-old man with a history of attention deficit hyperactivity disorder (ADHD) who was prescribed modafinil. While he initially experienced increased alertness, he began experiencing significant sleepiness, to the point where he was unable to work.
The symptoms continued even when he took a reduced dose of the medication, and worsened when the medication was stopped. The patient was hospitalized and, along with his wife, was treated for severe fatigue.
The patient's physicians determined that the simultaneous use of modafinil along with a prescription for sleep medication and amphetamines had led to his severe fatigue basically caused by overstimulation.
The case report concluded that the use of modafinil to treat ADHD is not without risk, and that users should be aware of the risks associated with the medication when combined with other drugs.
Modafinil-induced mood changes and psychosis
A case report involving another individual who experienced extreme fatigue while taking modafinil involved a 28-year-old man who, after being diagnosed with bipolar disorder, was prescribed the drug.
Although he had no history of psychiatric disorders prior to his treatment with modafinil, he experienced abnormal mood, decreased functional ability and propensity to engage in impulsive behavior while taking the drug.
He was diagnosed with bipolar disorder and prescribed olanzapine, another medication used to treat psychosis.
However, his symptoms were not adequately controlled and he continued to experience mood changes and psychosis even while taking olanzapine. The use of modafinil was discontinued, and the patient's psychotic symptoms resolved.
The case report concludes that modafinil may be associated with somnolence and psychiatric side effects, such as fatigue, lethargy, mania or apathy.
Modafinil is metabolized primarily by the cytochrome P450 3A4 (CYP3A4) enzyme. The risk of adverse effects from modafinil can be increased by the use of medications such as selective serotonin and norepinephrine reuptake inhibitors (SSRIs/SNRIs), which are also metabolized via CYP3A4.
Modafinil may also increase the metabolism of antipsychotic medications. Drugs that inhibit the CYP3A4 enzyme may decrease the metabolization of modafinil, and therefore increase its potential for adverse effects.
According to one case report, decreased clearance of modafinil resulted in a greater chance for fatigue, dizziness and somnolence in one individual treated with another medication known to inhibit CYP3A4 metabolism.
However, since the case report was anecdotal, further studies are needed to better identify new drug interactions that may be specific to modafinil. Using modafinil with caution
That being said, Modafinil on its own is considered to be relatively safe and well-tolerated.
Modafinil vs. Caffeine
There are numerous studies that examine the pharmacological effects of modafinil and caffeine, but most have been performed on laboratory animals or humans with other psychiatric conditions.
One study examined the effects of caffeine in healthy volunteers, while another examined the effects of modafinil in healthy individuals.
The study found that caffeine, which increases alertness in healthy individuals, had little effect on individuals with ADHD.
Modafinil however, was found to improve cognition by increasing arousal. The study concluded that although both caffeine and modafinil have different effects on the brain, they both increase wakefulness.
How to combat fatigue while taking modafinil
If the onset of fatigue while taking modafinil seems to be related to drug interactions, discontinuing the use of any drugs that may be interacting with the medication or that may have been prescribed to treat symptoms associated with modafinil use should help alleviate feelings of fatigue.
Increased exercise and modification of diet are two other ways to potentially reduce fatigue during modafinil treatment.
If you have any pre-existing sleep disorders or medical conditions, speak with your physician before taking modafinil.
If you experience fatigue while taking modafinil, discontinue the use of the medication and speak to a healthcare provider about potential alternatives.