What are the side effects of modafinil (Provigil)?

Modafinil Side Effects

Modafinil commonly causes headache, insomnia, nausea, diarrhea, and dry mouth, with rare but serious risks including severe skin reactions (Stevens-Johnson Syndrome), psychiatric symptoms, and cardiovascular effects. 1, 2

Common Side Effects

The most frequently reported adverse effects with modafinil include:

• Headache occurs in approximately 50% of patients and is the most common side effect 2, 3
• Insomnia and sleep disturbances are frequently reported, particularly when taken too close to bedtime 1, 3, 4
• Gastrointestinal symptoms including nausea, diarrhea, dyspepsia, dry mouth, and upset stomach 1, 2, 3
• Decreased appetite and weight loss, particularly concerning in children and adolescents 2, 5
• Anxiety and nervousness, including feelings of unease or restlessness 2, 3, 4
• Dizziness and lightheadedness 2, 3
• Back pain and stuffy nose 3

Most adverse events are mild to moderate in severity and rarely lead to medication discontinuation 5, 6.

Serious Side Effects Requiring Immediate Medical Attention

Severe Dermatological Reactions

Stop modafinil immediately and seek emergency care if you develop any skin reactions. 3

• Stevens-Johnson Syndrome (SJS) and severe rashes have been reported, particularly in pediatric populations 2, 5, 4
• The FDA issued a black box warning for pediatric patients due to cases of SJS during pivotal studies 2, 5
• Symptoms include skin rash, hives, sores in mouth, skin blistering and peeling 3
• Stopping the medication may not prevent the rash from becoming life-threatening or causing permanent disability or disfigurement 3

Serious Allergic Reactions

Discontinue modafinil immediately if you experience: 3

• Swelling of face, eyes, lips, tongue, or throat
• Trouble swallowing or breathing
• Fever, shortness of breath, leg swelling
• Yellowing of skin or whites of eyes (jaundice)
• Dark urine

These reactions may affect the liver or blood cells and can be life-threatening, requiring hospitalization 3.

Psychiatric and Neurological Effects

Modafinil can cause or worsen mental health problems. 2, 3

• Depression and worsening of existing depressive symptoms 2, 3
• Anxiety and agitation 4, 6
• Psychosis, including hallucinations (hearing, seeing, feeling, or sensing things that are not real) 2, 3
• Mania (extreme increase in activity and talking) 2, 3
• Suicidal thoughts, particularly noted in pediatric populations 2
• Aggressive behavior and other mental problems 3
• Hypersexuality has been reported with high-dose use (rare) 7

Cardiovascular Effects

Monitor for symptoms of heart problems: 3, 4

• Chest pain or discomfort
• Abnormal heartbeat
• Trouble breathing
• Elevated blood pressure and heart rate

Blood pressure should be checked more frequently while taking modafinil, especially in patients with pre-existing hypertension 3, 4.

Special Population Considerations

Pregnancy and Contraception

Modafinil may cause fetal harm and reduces the effectiveness of hormonal contraception. 1, 2

• A 2018 pregnancy registry report showed higher rates of major congenital anomalies in children exposed to modafinil/armodafinil in utero 1
• Animal data suggest potential fetal harm, though human data remain insufficient 1, 2
• Hormonal birth control methods (pills, shots, implants, patches, vaginal rings, IUDs) may not work while taking modafinil 3
• Women using hormonal contraception have a higher chance of pregnancy while on modafinil and for one month after stopping 3
• Alternative or additional contraceptive methods should be discussed 3

Pediatric Populations

Modafinil is NOT approved for use in children for any medical condition, including ADHD. 2, 3

• Higher frequency of adverse events in children and adolescents, likely due to higher weight-based dosing 6
• Increased risk of serious dermatological reactions including SJS 2, 5
• Side effects in pediatric studies included: Tourette's syndrome, hostile behavior, increased cataplexy, hallucinations when falling asleep, suicidal thoughts, low white blood cell count, and painful menstrual periods 3

Hepatic and Renal Impairment

• Reduce dose in elderly patients and those with hepatic disease 6
• Use caution in severe renal insufficiency due to substantial increases in modafinil acid levels 6

Abuse and Dependence Potential

Modafinil is a Schedule IV federally controlled substance due to potential for abuse or dependency. 1, 2, 3

• While abuse potential is considered lower than traditional stimulants, cases of modafinil dependence have been reported 4, 7
• Effects on the brain are similar to other stimulants, which may lead to abuse or dependence 3
• Keep modafinil in a safe place to prevent misuse; selling or giving away is against the law 3

Drug Interactions

Modafinil induces and inhibits several cytochrome P450 enzymes, creating potential for numerous drug interactions. 6

• May interact with medications from all drug classes 6
• Discuss all medications with your physician before starting modafinil 3

Important Safety Warnings

• Do not drive or operate dangerous machinery until you know how modafinil affects you 3
• Avoid alcohol while taking modafinil, as the interaction effects are not fully known 3
• Modafinil treats excessive sleepiness but does not cure underlying sleep disorders and does not replace adequate sleep 3
• Continue all prescribed treatments for underlying conditions (such as CPAP for obstructive sleep apnea) 3, 6