Abstract
To The Editor:
F
Case Report
X was an 8-year-old African American male weighing 28.6 kg, with no past psychiatric history, who was initially brought in by his mother for the treatment of his oppositional behavior and crying spells. On further evaluation, it was determined that he had been hyperactive, impulsive, and inattentive and met criteria for attention-deficit/hyperactivity disorder (ADHD). In addition, he also reported multiple depressive symptoms, including depressed mood, loss of interest, decreased energy level, and poor concentration. He was started on methylphenidate 5 mg twice daily, given the fact that his brother, who had had similar symptoms, responded very well to methylphenidate. Methylphenidate dose was increased to 10 mg twice daily 1 week later. Because the patient's mother reported increased physical aggression on this higher dose, it was titrated down to 5 mg twice daily. The patient was started on fluoxetine 4 mg daily for depression, after having been on methylphenidate for 2 weeks. This regimen was continued for 3 more weeks, after which the methylphenidate dose was increased to 10 mg twice daily, after ascertaining that the increased physical aggression was not caused by methylphenidate. While on this dose of methylphenidate for another week, the patient reported a sensation that he described as “ants crawling over his skin,” while he was watching television. He denied any visual or auditory hallucinations. This sensation lasted a few minutes and resolved on its own. Two days later, the patient woke up early because of a similar sensation over his skin and face, looking for ants over his body. He walked with caution, thinking that there might be ants on the floor. The sensation lasted for ∼1 hour and then went away. Subsequently, the patient had this sensation off and on, approximately once a day, and it scared him. These tactile hallucinations were thought to be secondary to methylphenidate. Methylphenidate was discontinued after ∼7 weeks of treatment. The tactile hallucinations persisted even 1 week after methylphenidate was discontinued. Fluoxetine was discontinued as well, a week after stopping methylphenidate. The tactile hallucinations became less frequent, and they resolved completely 2 weeks after discontinuation of fluoxetine. Methylphenidate was resumed 1 month after the disappearance of the tactile hallucinations. Methylphenidate dose was titrated up gradually to 15 mg three times a day, with no recurrence of tactile hallucinations. Fluoxetine was not reintroduced, as it would have been unethical to restart it given the debilitating side effect and suffering it caused to the patient.
Discussion
Tactile, visual and auditory hallucinations are commonly reported side effects of methylphenidate and other stimulant medications. However, tactile hallucinations are rare with fluoxetine or the combination of fluoxetine with other medications. Here, we report tactile hallucinations that started while the patient was on a combination of fluoxetine and methylphenidate. These hallucinations did not subside after the discontinuation of methylphenidate, but resolved 2 weeks after discontinuation of fluoxetine. Methylphenidate has a half-life of 2–3 hours and most hallucinations subside a few days after its discontinuation. The fact that they persisted for weeks after its discontinuation hints toward fluoxetine being the primary causal agent. Fluoxetine has a longer half-life, hence it could be responsible for the persistent hallucinations. The combination of methylphenidate and fluoxetine can increase the blood fluoxetine level as well, thus increasing the propensity for side effects. Ungerleider and associates proposed that d-lysergic acid diethylamide (LSD) mediates hallucinations by an agonist effect at the postsynaptic 5-HT2 receptor. Using this model, it is possible to draw comparisons to the clinical picture associated with fluoxetine-induced tactile hallucinations (Glennon et al. 1984; Ungerleider et al 1992). Another cause for the tactile hallucinations in this child could have been methylphenidate. Methylphenidate can result in the reduction of brain dopamine transporter density in the striatal system, leading to dopamine flooding in the synapse, hence resulting in hallucinations (Vles et al. 2003). Another hypothesis could be the lack of serotonin in depression, leading to serotonin receptor hypersensitivity. Fluoxetine increases serotonin in the ventral striatum, stimulating these possibly hypersensitized 5-HT3 receptors. This may lead to an exaggerated ventral striatal dopamine release in response to methylphenidate itself, producing tactile hallucinations (Lauterbach 1991). Prescribing physicians should be aware of this side effect, especially when fluoxetine is combined with methylphenidate, as it can affect compliance.
Footnotes
Disclosures
The authors have no conflicts of interest or financial ties to report.