Side Effects of modafinil: A Synthesis of Findings from 25 Studies

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Original Abstract of the Article

Main Research Findings

Modafinil is a wakefulness-promoting agent used to treat sleep disorders such as narcolepsy, shift work sleep disorder, and obstructive sleep apnea syndrome. 16 , 12 . Modafinil is also used off-label to enhance cognitive function. 3 . However, modafinil can cause side effects, some of which are serious. 24 , 1 , 2 , 25 , 15 , 8 . Modafinil is thought to promote wakefulness by inhibiting the reuptake of dopamine and norepinephrine. 22 . However, the mechanism of action of modafinil is not fully understood. 1 .

Reasons for Side Effects

The side effects of modafinil may be related to its action of inhibiting the reuptake of dopamine and norepinephrine. 22 . Dopamine and norepinephrine are involved in important brain functions such as mood, wakefulness, attention, and motor control. When modafinil inhibits the reuptake of these neurotransmitters, levels of these neurotransmitters in the brain may increase, leading to side effects.

Common Side Effects

Headache

Modafinil can cause headaches. 12 , 11 . Headaches may be caused by modafinil inhibiting the reuptake of dopamine and norepinephrine. 22 .

Gastrointestinal Symptoms

Modafinil can cause gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and diarrhea. 12 , 2 , 11 . These symptoms may be caused by modafinil directly affecting the gastrointestinal tract.

Psychoneurological Symptoms

Modafinil can cause psychoneurological symptoms, such as anxiety, insomnia, dizziness, hallucinations, and manic episodes. 2 , 11 , 15 . These symptoms may be caused by modafinil increasing levels of dopamine and norepinephrine in the brain. 22 .

Skin Symptoms

Modafinil can cause skin symptoms, such as rash, itching, erythema, and Stevens-Johnson syndrome (SJS). 24 , 25 . These symptoms may be caused by modafinil causing an allergic reaction.

Cardiovascular Symptoms

Modafinil can cause cardiovascular symptoms, such as increased heart rate, increased blood pressure, atrial fibrillation, and ventricular tachycardia. 24 , 15 , 8 . These symptoms may be caused by modafinil directly affecting the heart.

Other Side Effects

Modafinil can cause other side effects, such as decreased appetite, weight loss, dry mouth, and changes in libido. 2 , 9 , 18 . These symptoms may be caused by modafinil affecting various neurotransmitters in the brain.

Side Effect Countermeasures

Headache

If you experience a headache, consult your doctor. If your headache is severe, stop taking modafinil and follow your doctor's instructions.

Gastrointestinal Symptoms

If you experience gastrointestinal symptoms, consult your doctor. If your gastrointestinal symptoms are severe, stop taking modafinil and follow your doctor's instructions.

Psychoneurological Symptoms

If you experience psychoneurological symptoms, consult your doctor. If your psychoneurological symptoms are severe, stop taking modafinil and follow your doctor's instructions.

Skin Symptoms

If you experience skin symptoms, consult your doctor immediately. If your skin symptoms are severe, stop taking modafinil and follow your doctor's instructions.

Cardiovascular Symptoms

If you experience cardiovascular symptoms, consult your doctor immediately. If your cardiovascular symptoms are severe, stop taking modafinil and follow your doctor's instructions.

Comparison Between Studies

Commonalities of Studies

Many studies have shown that modafinil can cause side effects. 24 , 1 , 2 , 25 , 15 , 8 . These studies have reported a variety of side effects, including headache, gastrointestinal symptoms, psychoneurological symptoms, skin symptoms, and cardiovascular symptoms.

Differences Between Studies

The types and frequencies of side effects that modafinil can cause vary from study to study. Some studies have shown that modafinil side effects are more frequent in certain populations. For example, the study in 24 showed that modafinil is very effective in patients with myotonic dystrophy type 1. However, the study in 8 showed that modafinil can cause myocardial ischemia in rats when administered at high doses. These research results show that while modafinil is an effective drug, it carries a risk of side effects.

Precautions for Real-life Application

While modafinil is an effective drug for treating sleep disorders, it also carries the risk of side effects. 24 , 1 , 2 , 25 , 15 , 8 . When using modafinil, it is important to consult your doctor and understand the risks and benefits of side effects. In particular, modafinil can cause myocardial ischemia when administered at high doses. 8 . Also, modafinil can be addictive. 2 . Do not take modafinil on your own, follow your doctor's instructions.

Limitations of Current Research

Not enough research has been done on the side effects of modafinil. In particular, there is still much that is unknown about the long-term side effects of modafinil. Additionally, the side effects of modafinil can vary from person to person.

Future Research Directions

Further research is needed on the side effects of modafinil. In particular, research needs to be conducted on the long-term side effects of modafinil, the reasons why modafinil side effects are more frequent in certain populations, and ways to reduce the side effects of modafinil.

Conclusion

Modafinil is an effective drug for treating sleep disorders, but it also carries the risk of side effects. 24 , 1 , 2 , 25 , 15 , 8 . When using modafinil, it is important to consult your doctor and understand the risks and benefits of side effects. Do not take modafinil on your own, follow your doctor's instructions.

Literature analysis of 25 papers
Positive Content
16
Neutral Content
1
Negative Content
8
Article Type
4
0
1
3
21
1.

Modafinil disrupts prepulse inhibition in mice: strain differences and involvement of dopaminergic and serotonergic activation.

Author: KwekPerrin, van den BuuseMaarten

PPI disruption

This study investigated the effect of modafinil on prepulse inhibition (PPI) in mice, finding that modafinil disrupts PPI in a strain-dependent manner through dopamine D2 and 5-HT2A receptor activation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Modafinil Dependence and Hypersexuality: A Case Report and Review of the Evidence.

Author: SwapnajeetSahoo, BnSubodh, GouravGupta

Wakefulness promotion
Dependence
Hypersexuality

Modafinil is a medication used for narcolepsy and other conditions. This study presents a case report of a patient who developed modafinil dependence and hypersexuality after increasing his modafinil dosage.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

3.

A State-of-the-Art Review on the Use of Modafinil as A Performance-enhancing Drug in the Context of Military Operationality.

Author: Van PuyveldeMartine, Van CutsemJeroen, LacroixEmilie, PattynNathalie

Modafinil cognitive performance
Modafinil side effects

This review presents a current state-of-the-art and research agenda on modafinil as a smart drug. The review examines four research questions related to the effects of modafinil on cognitive performance in a non-military context.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial.

Author: NourbakhshBardia, RevirajanNisha, MorrisBridget, CordanoChristian, CreasmanJennifer, ManguinaoMichael, KryskoKristen, RutatangwaAlice, AuvrayCaroline, AljarallahSalman, JinChengshi, MowryEllen, McCullochCharles, WaubantEmmanuelle

MS fatigue treatment

This study compares the efficacy of methylphenidate, modafinil, and amantadine against placebo for alleviating fatigue in multiple sclerosis patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Pragmatic Clinical TrialA trial conducted in a real-world clinical setting. It evaluates the effectiveness of interventions in everyday healthcare environments.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Beliefs About Medicines Predict Side-Effects of Placebo Modafinil.

Author: HellerMonika K, ChapmanSarah C E, HorneRob

None
Nocebo Effect

This study investigated the nocebo effect, where patients taking a placebo report side effects. The study found that people who believe pharmaceuticals are harmful, are more sensitive to medication, have concerns about the drug, and experience negative emotions are more likely to experience nocebo effects. This suggests that beliefs about medication can influence the experience of side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Modafinil's effects on cognition and sleep quality in affectively-stable patients with bipolar disorder: a pilot study.

Author: LipschitzJessica M, Perez-RodriguezMercedes, MajdMarzieh, LarsenEmmett, LocascioJoseph, PikeChelsea K, ShanahanMegan, BurdickKatherine E

This study investigated the feasibility, safety, and preliminary efficacy of modafinil, a wake-promoting drug, for improving neurocognitive function, daytime sleepiness, and sleep quality in affectively-stable patients with bipolar disorder (BD).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

Reining in the pharmacological enhancement train: we should remain vigilant about regulatory standards for prescribing controlled substances.

Author: Drabiak-SyedKatherine

Addiction
Side effects

This article challenges the ethical and legal implications of prescribing psychopharmacological enhancement drugs to patients. Prescribing a controlled substance such as modafinil for performance enhancement and sleep avoidance runs contrary to a physician's ethical duty to the patient and the standard of practice set forth in legal requirements governing the prescription of controlled substances.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Efficacy of modafinil on excessive daytime sleepiness in Prader-Willi syndrome.

Author: De CockV Cochen, DieneG, MolinasC, MassonV Dauriac-Le, KiefferI, MimounE, TibergeM, TauberM

Treat sleepiness

This open-label pilot study evaluated the efficacy of modafinil in reducing excessive daytime sleepiness in children and adolescents with Prader-Willi Syndrome (PWS). Modafinil significantly improved sleepiness in all nine patients. No side effects were reported.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

11.

Cataplexy as a side effect of modafinil in a patient without narcolepsy.

Author: LopesEduardo, PereiraDanielle, da Silva BehrensNilce Sanny Costa, de Almeida FonsecaHassana, CalvancantiPaola Oliveira, de Araújo LimaTaís Figueiredo, Pradella-HallinanMarcia, CastroJuliana, TufikSergio, CoelhoFernando Morgadinho Santos

Sleepiness treatment
Side effects

Modafinil is a commonly used treatment for narcolepsy. This study describes an unexpected side effect of modafinil in a patient with an incorrect diagnosis of narcolepsy.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

12.

Experience with the use of modafinil in the treatment of narcolepsy in a outpatient facility specialized in diurnal excessive sleepiness in São Paulo.

Author: da Silva BehrensNilce Sanny Costa, LopesEduardo, PereiraDanielle, de Almeida FonsecaHassana, Oliveira CavalcantiPaola, de Araújo LimaTaís Figueiredo, Pradella-HallinanMarcia, CastroJuliana, TufikSergio, Santos CoelhoFernando Morgadinho

narcolepsy treatment
diarrhea
headache
paresthesias

Modafinil is a commonly used treatment for narcolepsy. This study evaluates the use of modafinil in a sample of narcoleptic patients in Brazil.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

14.

Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study.

Author: LohrJames B, LiuLianqi, CaligiuriMichael P, KashTaylor P, MayTodd A, MurphyJody Delapena, Ancoli-IsraelSonia

Improved parkinsonism

Modafinil improved parkinsonian symptoms in patients with schizophrenia or schizoaffective disorder, but did not significantly affect negative symptoms, cognitive function, or sleepiness.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Modafinil-induced ventricular arrhythmia: A case report.

Author: MutluDeniz, KültürsayBarkın, KaragözAli

Narcolepsy treatment
Wakefulness promotion
Arrhythmic events
Cardiovascular side effects
Drug abuse

A 23-year-old female experienced recurrent palpitations after taking modafinil to enhance her cognitive performance. This case report highlights the potential cardiovascular side effects of modafinil, even in healthy individuals, and emphasizes the importance of careful monitoring and assessment of patients taking this medication.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

16.

The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial.

Author: BoeleFlorien W, DouwLinda, de GrootMarjolein, van ThuijlHinke F, CleijneWilmy, HeimansJan J, TaphoornMartin J B, ReijneveldJaap C, KleinMartin

Cognitive function
Depression reduction
Fatigue reduction
Quality of life

Modafinil effectively improved fatigue, depression, and cognitive functioning in patients with primary brain tumors (PBTs).

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy.

Author: SarfrazNoeen, OkuampaDavid, HansenHannah, AlvarezMark, CornettElyse M, KakazuJuyeon, KayeAdam M, KayeAlan D

Cataplexy treatment
EDS treatment

Pitolisant, a novel histamine-3 receptor (H3R) antagonist, has shown promising results in treating excessive daytime sleepiness (EDS) and cataplexy in adults with narcolepsy. Studies have indicated that Pitolisant is non-inferior to Modafinil in treating EDS but superior in reducing cataplexy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

On-demand d-modafinil may be an effective treatment option for lifelong premature ejaculation: a case report.

Author: SerefogluE C

Increased IELT
Heartburn
Insomnia

On-demand d-modafinil seems to be an effective treatment for men with lifelong premature ejaculation. The side effects were transient and mild in the reported case.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

Comparison of the Efficacy, Side Effects, and Cost of Modafinil and Intranasal Mometasone Furoate in Obstructive Sleep Apnea-Hypopnea Syndrome: A Preliminary Clinical Study.

Author: ZhangShujia, FuJing, DuanZhongnin

OSAHS treatment

Intranasal mometasone furoate was found to be more effective than modafinil in treating obstructive sleep apnea-hypopnea syndrome (OSAHS), with fewer side effects and a lower cost.

Clinical StudyResearch involving human participants to assess the safety, efficacy, and effects of an intervention/treatment.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

21.

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity.

Author: ShanmugasundaramBharanidharan, AherYogesh D, AradskaJana, IlicMarija, Daba FeyissaDaniel, KalabaPredrag, AherNilima Y, DragacevicVladimir, Saber MaroufBabak, LangerThierry, SitteHarald H, HoegerHarald, LubecGert, KorzVolker

Cognitive enhancement
Memory improvement

This study explored the cognitive enhancing properties of R-Modafinil, an enantiomer of modafinil, in a spatial memory paradigm and its effects on dentate gyrus long-term potentiation (DG-LTP). R-Modafinil enhanced spatial reference memory and rescued DG-LTP from the impairing effects of DMSO. These findings suggest that R-Modafinil may improve cognitive function by enhancing synaptic plasticity, potentially involving dopamine receptor D1.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

23.

Open-label placebo treatment does not enhance cognitive abilities in healthy volunteers.

Author: HartmannHelena, ForkmannKatarina, SchmidtKatharina, Kleine-BorgmannJulian, AlbersJohanna, WiechKatja, BingelUlrike

OLP limitations

Modafinil is a medication that is sometimes used to improve cognitive performance. This study investigated the effects of open-label placebo (OLP) treatment, in which individuals are told they are receiving an inactive treatment, on cognitive performance in healthy volunteers. OLP treatment did not improve any measures of cognitive performance in this study.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

25.

Fixed drug eruptions with modafinil.

Author: GhoshalLoknath, SinhaMausumi

Narcolepsy treatment
Fixed drug eruption

Modafinil, a psychostimulant drug, has been reported to cause fixed drug eruption (FDE), a distinctive reaction pattern characterized by recurring eruptions at the same site. This report highlights two cases of modafinil-induced FDE and emphasizes the need for increased awareness of potential adverse effects, especially given the rising misuse of this drug.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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