Case summary
In this report, Niijima and colleagues describe a 24-year-old Japanese woman with autism spectrum disorder (ASD) and excessive daytime sleepiness ultimately diagnosed as narcolepsy type 2.
The patient had a longstanding history of ASD treated with aripiprazole and biperiden for more than 10 years. After discontinuation of both medications for sleep evaluation, polysomnography and multiple sleep latency testing confirmed narcolepsy type 2. Modafinil was initiated at 100 mg/day and later increased to 200 mg/day because of insufficient improvement in daytime sleepiness.
Approximately 2 weeks after dose escalation, the patient developed involuntary orofacial and right-sided limb movements characterized by mumbling and slow twisting motions resembling tardive dyskinesia. Extensive biochemical evaluation showed no metabolic, endocrine, or electrolyte abnormalities, and no psychiatric destabilization was identified.
Modafinil-associated dyskinesia was suspected, and the medication was discontinued. Symptoms persisted for several weeks despite drug withdrawal, prompting treatment with Yi-Gan San, after which gradual improvement occurred with complete resolution approximately 5 months after symptom onset.
The authors propose that dysregulated striatal dopamine signaling associated with ASD, combined with residual dopamine D2 receptor alterations from chronic aripiprazole exposure, may have increased susceptibility to modafinil-induced dyskinesia.
Why this case matters
- Expands recognition of rare neurological adverse effects of modafinil
- Suggests ASD-related dopaminergic vulnerability may increase dyskinesia risk
- Highlights possible interaction between prior antipsychotic exposure and stimulant therapy
- Reinforces careful monitoring during modafinil dose escalation
Clinical Take-Home Message
Patients with autism spectrum disorder and prior chronic dopamine receptor–blocking therapy may be particularly vulnerable to dyskinesia after modafinil initiation or dose escalation, warranting close neurological monitoring.
Question
What factor most likely increased susceptibility to dyskinesia in this patient?
A. Severe sleep deprivation
B. Structural brain lesion
C. Prior chronic aripiprazole exposure with dopaminergic dysregulation
D. Thyroid dysfunction
Correct answer: C. Prior chronic aripiprazole exposure with dopaminergic dysregulation
Explanation:
The authors hypothesized that long-term dopamine D2 receptor alterations from chronic aripiprazole exposure, combined with altered striatal dopamine signaling in ASD and modafinil-mediated dopaminergic activation, contributed to dyskinesia development.
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