Modafinil Side Effects: What the Sources List, and Which the Trials Call Common
The FDA prescribing information for modafinil lists the modafinil side effects the placebo-controlled trials found most: headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.1 It warns of serious rash, psychiatric, and cardiovascular reactions, and the reviews report no preponderance of side effects in healthy users.45
Personal account, not medical advice. Modafinil is a prescription medicine, and a Schedule IV controlled substance in the United States. Nothing here is a recommendation to start, stop or change anything. Talk to a doctor.
What the trials called most common
The prescribing information states that in placebo-controlled clinical trials, the most common adverse reactions, at a rate of 5% or more, associated with the use of modafinil more frequently than placebo-treated patients were headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.1
Table 1 in the same label gives the pooled percentages across 934 modafinil-treated patients and 567 placebo-treated patients: headache 34% against 23%, nausea 11% against 3%, nervousness 7% against 3%, rhinitis 7% against 6%, back pain 6% against 5%, diarrhea 6% against 5%, anxiety 5% against 1%, dizziness 5% against 4%, dyspepsia 5% against 4%, and insomnia 5% against 1%.1 Headache is the effect the table reports most often, and the label names headache and anxiety as the two dose-related adverse reactions in the trials that compared three dose levels against placebo.1
The label adds that 74 of the 934 patients (8%) who received modafinil discontinued treatment because of an adverse reaction, compared with 3% of the placebo patients, and that headache, at 2%, was the most frequent single reason.1
It also carries the trial caveat that adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.1
What the consumer drug pages list as more and less common
Mayo Clinic's drug information page lists anxiety, headache, nausea, and nervousness as its more common set, and a longer less common set that includes back pain, belching, decrease in appetite, diarrhea, difficulty having a bowel movement, dryness of the mouth, dryness of the skin, flushing or redness of the skin, heartburn, indigestion, muscle stiffness, sour stomach, stomach discomfort, upset or pain, stuffy or runny nose, swelling, tingling, burning, or prickling sensations in the skin, and vomiting.3 The same page states that its drug information is provided by Merative, Micromedex.3
The page also carries a check-with-your-doctor list of effects it calls less common: black, tarry stools, blurred vision or other vision changes, chest pain, chills or fever, clumsiness or unsteadiness, confusion, dizziness or fainting, increased thirst and urination, mental depression, problems with memory, rapidly changing moods, shortness of breath, sore throat, trembling or shaking, trouble in urinating, uncontrolled movements of the face, mouth, or tongue, unusual bleeding or bruising, and unusual tiredness or weakness.3
Drugs.com's page for health professionals gives frequencies by body system. It lists headache, at up to 34%, and nausea, at up to 11%, as very common (10% or more); nervousness, anxiety, insomnia, and depression as common (1% to 10%); sleep disorder and aggression as uncommon (0.1% to 1%); and hallucinations, mania, and psychosis as rare (0.01% to 0.1%).2 Its dermatologic list marks rash, acne, and pruritus as uncommon, and its postmarketing reports name serious or life-threatening rash, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, along with urticaria and angioedema.2 Its hypersensitivity postmarketing reports name multi-organ system hypersensitivity reactions and anaphylaxis, and its cardiovascular list marks hypertension, palpitation, tachycardia, and vasodilation as common (1% to 10%).2
The serious reactions the label warns about
The prescribing information names seven serious reactions in its adverse reactions section: serious rash, including Stevens-Johnson syndrome; angioedema and anaphylaxis reactions; multi-organ hypersensitivity reactions; persistent sleepiness; psychiatric symptoms; effects on ability to drive and use machinery; and cardiovascular events.1
On rash, the label says serious rash requiring hospitalization and discontinuation of treatment has been reported in association with the use of modafinil.1 In the clinical trials, rash that led to discontinuation appeared in about 0.8% of pediatric patients (13 per 1,585), including one case of possible Stevens-Johnson syndrome and one case of apparent multi-organ hypersensitivity reaction, with no such cases among 380 pediatric patients who received placebo.1 Rare cases of serious or life-threatening rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, have been reported in adults and children in worldwide postmarketing experience.1 The label records that nearly all cases of serious rash appeared within 1 to 5 weeks after treatment began, with isolated cases reported after prolonged treatment of about three months.1 It adds that although benign rashes also occur with modafinil, it is not possible to reliably predict which rashes will prove to be serious.1
On allergic reactions, the label notes that angioedema and hypersensitivity, with rash, dysphagia, and bronchospasm, were observed in patients treated with armodafinil, the R enantiomer of modafinil, that no such cases were observed in the modafinil clinical trials, and that angioedema has been reported in postmarketing experience with modafinil.1 How the two compare is covered on the modafinil vs armodafinil page.
On multi-organ hypersensitivity, the label reports reactions that have included at least one fatality in postmarketing experience, occurring in close temporal association with starting modafinil (median time to detection 13 days, range 4 to 33), and says these may result in hospitalization or be life-threatening.1 Patients typically, although not exclusively, presented with fever and rash with other organ involvement, and associated manifestations included myocarditis, hepatitis, liver function test abnormalities, blood cell abnormalities, pruritus, and asthenia.1
On psychiatric symptoms, the label reports that in the adult controlled trials, psychiatric symptoms that led to treatment discontinuation, at a frequency of 0.3% or more and more often with modafinil than with placebo, were anxiety (1%), nervousness (1%), insomnia (under 1%), confusion (under 1%), agitation (under 1%), and depression (under 1%).1 Postmarketing adverse reactions have included mania, delusions, hallucinations, suicidal ideation, and aggression, some resulting in hospitalization, and many, but not all, of those patients had a prior psychiatric history.1
On cardiovascular events, the label reports that in the clinical studies, chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG occurred in three subjects in association with mitral valve prolapse or left ventricular hypertrophy, and that in a Canadian clinical trial, one participant with a prior history of syncopal episodes experienced a 9 second episode of asystole after 27 days of modafinil treatment (300 mg/day in divided doses).1 Blood pressure monitoring in the short-term controlled trials of three months or less showed no clinically significant changes in mean systolic and diastolic blood pressure with modafinil compared with placebo, while a retrospective analysis of antihypertensive use in these studies found that a greater proportion of patients on modafinil needed new or increased antihypertensive medication (2.4%) than patients on placebo (0.7%).1
What the two reviews say about healthy users
Battleday and Brem's 2015 systematic review searched MEDLINE for primary studies of the cognitive actions of modafinil in healthy non-sleep-deprived humans, from January 1990 through December 2014.4 On side effects, its abstract states: "Importantly, we did not observe any preponderances for side effects or mood changes."4 The same abstract reports that most of those studies using basic testing paradigms showed enhanced executive function, while only half showed improvements in attention and learning and memory, and a few reported impairments in divergent creative thinking.4 More of that review's ground is on the modafinil as a nootropic page.
Kim's 2012 review says modafinil "is known to have less or no adverse effects than those found in traditional psychostimulants such as amphetamine, methylphenidate or cocaine."5 It also records that modafinil increases resting heart rate and blood pressure, and that its use "could be restricted to patients with heart disease because it causes excessive peripheral autonomic activation."5 A few of the studies it cites reported that modafinil impairs recovery sleep under sleep deprivation, even though the alertness and cognitive effects were significant.5
What the sources cover on long-term use
One placebo-controlled trial in the prescribing information monitored the effects of modafinil withdrawal after 9 weeks of use: no reported withdrawal symptoms during 14 days of observation, although sleepiness returned in narcoleptic patients.1 The modafinil withdrawal symptoms page covers that topic.
The same label records a laboratory pattern from the placebo-controlled trials: mean plasma levels of gamma glutamyltransferase and alkaline phosphatase were higher after modafinil than after placebo, and shifts to higher, but not clinically significantly abnormal, values appeared to increase with time in the modafinil-treated population.1
Drugs.com's page addresses dependence for long-time or large-dose use: its precautions name a strong desire or need to continue taking the medicine, a need to increase the dose for the same effect, and withdrawal side effects when the medicine is stopped as the signs to bring to a doctor.2
Battleday and Brem's abstract reports no preponderances for side effects or mood changes across the studies of healthy non-sleep-deprived humans it reviewed.4 Kim's review calls the classification of modafinil as addictive still controversial, and reports possible setbacks of abuse and addiction in the papers it cites, with no cases reported to date.5
The short version
The prescribing information and the two drug pages each list headache, nausea, and nervousness among their common sets,123 the label's serious-reaction warnings cover rash, psychiatric, and cardiovascular events,1 and the reviews report no preponderance of side effects in healthy users.45
Related pages: modafinil withdrawal symptoms, modafinil vs armodafinil, and modafinil as a nootropic.
Written by The Night Owl, a long-term user of modafinil who is not a doctor, pharmacist or healthcare provider. This page describes one person's experience alongside published research. It is not medical advice.
Sources
1: DailyMed (prescribing information). Modafinil tablet prescribing information. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=013450dd-cd42-46c7-98d6-9a2925761978
2: Drugs.com. Modafinil Side Effects: Common, Severe, Long Term. Internet Archive snapshot, 1 May 2026. https://web.archive.org/web/20260501011343/https://www.drugs.com/sfx/modafinil-side-effects.html
3: Mayo Clinic. Modafinil (Oral Route). Internet Archive snapshot, 8 November 2025. https://web.archive.org/web/20251108060034/https://www.mayoclinic.org/drugs-supplements/modafinil-oral-route/description/drg-20064870
4: Battleday R.M., Brem A.K. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. European Neuropsychopharmacology. 2015. https://pubmed.ncbi.nlm.nih.gov/26381811/
5: Kim D. Practical use and risk of modafinil, a novel waking drug. Environmental Health and Toxicology. 2012. https://pmc.ncbi.nlm.nih.gov/articles/PMC3286657/