Dear Editor:

We thank the author for their thoughtful and insightful comments on our case report.¹ We fully agree that fluoxetine has a known potential to trigger seizures, especially in overdose situations. In our patient, who ingested approximately 2,000mg of fluoxetine, well above therapeutic doses, the development of a generalized tonic-clonic seizure within hours aligns with what has been documented in the literature. Our case reinforces these findings and underscores the importance of careful prescribing and monitoring, especially in individuals who may be at risk for overdose or adverse effects.

We also appreciate the mention of fluoxetine’s anticonvulsant properties in certain rare genetic epilepsies, such as those involving KCNT1 mutations. However, our patient did not have a history of drug-resistant seizures or any indication of genetic epilepsy syndrome. Given the acute context of a large intentional overdose in someone without prior seizures, we believe fluoxetine intoxication remains the most plausible explanation for the seizure event. While fluoxetine may have beneficial effects in specific epilepsy subtypes, this does not negate its recognized proconvulsant effects in overdose.

Regarding the role of pharmacogenomics, we acknowledge that cytochrome P450 polymorphisms (particularly CYP2D6 and CYP2C19) can influence fluoxetine metabolism and toxicity risk. Unfortunately, pharmacogenetic testing was not performed in our patient’s case as it is not routinely recommended in the clinic care setting. We agree that genotyping may provide valuable information for individualized risk assessment and could guide closer monitoring or prophylactic measures in susceptible patients.

We would also like to clarify the clinical course concerning seizure activity. The patient experienced a single generalized tonic-clonic seizure lasting approximately 90 seconds. Lorazepam was administered as a precaution to reduce the risk of recurrent seizures, not to treat status epilepticus.

Finally, we acknowledge the suggestion to consider alternative causes of seizure. The patient underwent emergent noncontrast computed tomography (CT), which was normal. Given the acute overdose and prompt recovery without neurological deficits, brain magnetic resonance imaging (MRI) was not pursued during hospitalization. While MRI is more sensitive for detecting subtle structural abnormalities, the clinical picture strongly supported a toxic etiology. Infectious and autoimmune encephalitis was considered unlikely due to the absence of fever, meningeal signs, or persistent altered mental status, so lumbar puncture was not performed. Although ASD is associated with a higher seizure risk, our patient had no prior seizure history. We recognize that genetic factors can influence seizure susceptibility in ASD, but the clear temporal relationship with fluoxetine overdose makes alternative causes less probable.

In summary, we appreciate the comprehensive feedback and hope this response clarifies the clinical reasoning and limitations in our case report.

With regards,

Danya Ansari, MD; Mahnoor Waqar, MD; and Sadiq Naveed, MD, MPH

Drs. Ansari and Waqar are resident physicians at the Eastern Connecticut Health Network in Manchester, Connecticut. Dr. Naveed is the psychiatry program director at the Eastern Connecticut Health Network in Manchester, Connecticut.

Funding/financial disclosures. The authors have no conflicts of interest relevant to the content of this letter. No funding was received for the preparation of this letter.

Reference

1. Allen MA, Ansari D, Naveed S. Fluoxetine-induced seizure: a case report and review of literature. Innov Clin Neurosci. 2024;21
   (10–12):22–24.