Document Type

Article

Publication Title

Discover Neuroscience

Abstract

Context

Modafinil is a central-acting wakefulness-promoting agent approved for narcolepsy, obstructive sleep apnea, and shift-work sleep disorder and is increasingly prescribed off-label for several neuropsychiatric conditions. Due to its favorable safety profile and lower abuse potential compared with other psychostimulants, modafinil has been increasingly used in treatment for narcolepsy and similar sleep disorders. While its safety profile is generally applauded, there have been an increasing number of case reports detailing rare neuropsychiatric adverse effects associated with modafinil exposure.

Objective

This systematic review aims to evaluate published case reports of modafinil-associated psychosis in order to characterize patient demographics, clinical presentation, and outcomes.

Methods

A systematic search of the literature describing psychosis temporally associated with modafinil exposure was conducted using PubMed and Embase on January 24, 2026, identifying case reports published since database inception. Search terms included “modafinil” and “psychosis.” Articles were included if they reported confirmed modafinil exposure with the development of psychiatric symptoms. Non-English articles without translation and reports lacking a clear temporal association were excluded. The articles were screened to ensure the inclusion criteria were met, and the likelihood of a causal relationship between modafinil and the reported psychotic event was assessed using the Naranjo Adverse Drug Reaction Probability Scale. Any discrepancies regarding study eligibility were resolved by the researchers utilizing the Joanna Briggs Institute critical appraisal guidelines.

Results

A total of seven articles with nine cases met the inclusion criteria, with the average age being 47.1 years, and a predominance of male patients. Clinical presentation most often included agitation, hallucinations, and delusions, as seen in almost half of the patients. Less frequently, patients expressed manic symptoms, suicide attempts, and disorganized behavior. Psychotic symptoms occurred at doses ranging from 100 to 400 mg and with onset ranging from 48 h to approximately 21 days after initiation, with no clear dose-dependent pattern observed. Patients with a previous psychiatric history appeared to be more vulnerable to developing symptoms. Management universally involved discontinuation of modafinil, with supportive psychiatric treatment when necessary. Complete symptom resolution occurred in 77.8% of cases, while partial improvement was reported in 22.2%. No cases reported persistent psychosis during available follow-up.

Conclusion

The findings of this review highlight the importance of recognizing modafinil-associated psychosis as a rare but clinically significant adverse effect, necessitating clinician vigilance when prescribing the medication, particularly in patients with underlying psychiatric vulnerabilities. Early recognition of neuropsychiatric symptoms may allow for timely discontinuation of the medication and prevent escalation of psychiatric complications. Awareness of this rare but meaningful adverse effect may help clinicians more carefully weigh the benefits of modafinil against its potential neuropsychiatric risks and guide safer prescribing decisions.

DOI

10.1186/s13064-026-00325-x

Publication Date

8-29-2026

ISSN

3005-1827

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