Innov Clin Neurosci. 2025;22(4–6):11–13.

Dear Editor:

We read with interest the article by Free et al¹ about a 32-year-old female patient with a history of migraine, gastroesophageal reflux disease (GERD) and gastroparesis, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder, depression, and anxiety, who was also diagnosed with nonspecific bipolar disorder due to a history of mood swings with predominant agitation, anger, and impulsive decisions. Lamotrigine led to stabilization of mood, but the addition of amphetamine mixed salts (MAS) caused compulsive chewing.¹ The causal relationship between compulsive chewing and MAS was demonstrated by the fact that reducing the dose of MAS led to an improvement in symptoms.¹ The study is convincing, but some points should be discussed.

The first point is that different causes for compulsive chewing were not sufficiently ruled out. It was only mentioned that the patient did not have bruxism or jaw tension.¹ Therefore, to rule out a cerebral disorder, it would have been imperative to perform cerebral imaging, preferably by magnetic resonance imaging (MRI). Has the patient ever undergone cerebral imaging since the onset of compulsive chewing? Patients might develop the urge to chew not only due to the use of MAS, but also due to structural lesions of the brain, such as a hypothalamic hamartoma.² In this context, the results of electroencephalography (EEG) recordings are also lacking. Since chewing can be the clinical correlate of a seizure,³ it would have been imperative to rule out epilepsy as the cause of compulsive chewing. 

The second point is that reducing the MAS dose to 2.5mg per day led to a reduction in compulsive chewing and increasing the dose to 5mg per day in turn led to a recurrence of the compulsive behavior, which then resolved spontaneously after a few days.¹ How can it be explained that reducing the dose initially had a positive effect and that increasing the dose after the initial recurrence of the behavior was accompanied by a spontaneous cessation? 

The third point is that the time course of the medication is not well presented. According to the case description, the patient was taking MAS extended-release (XR) 10mg per day.¹ When was this dose discontinued? How many days or weeks was the patient free of MAS before starting MAS immediate-release (IR) 2.5mg? How many days after starting MAS IR did orofacial automatism occur?

The fourth point is that a single case cannot provide reliable information about the effects and side effects of a drug. To confirm or exclude compulsive chewing as a side effect of MAS, more in-depth studies are required. Since the patient was not only taking MAS but also at least lamotrigine, a side effect caused by the combination of two drugs cannot be ruled out.

The fifth point is that the study by Dickson et al⁴ was not discussed. In this study, Sprague-Dawley rats were implanted with bilateral cannulas directed to one of eight striatal subareas and were injected with either saline or amphetamine in an opposing order.⁴ Amphetamine injections into the mid-ventrolateral striatum resulted in intense stereotypy consisting primarily of bar biting, noninjurious self-biting, and repetitive paw-to-mouth movements, while having no effect on locomotion or rearing.⁴ Amphetamine injections 2mm medial or 1mm dorsal produced no oral stereotypies, while injections 1mm rostral or caudal to the site of action produced only minor stereotypies.⁴ 

Overall, it can be said that this interesting study has limitations that put the results and their interpretation into perspective. Addressing these limitations could strengthen the conclusions and improve the study’s message. Before compulsive chewing is attributed to MAS, alternative causes must be thoroughly ruled out.

With regards,

Josef Finsterer, MD, PhD

Dr. Finsterer is with Neurology and Neurophysiology Center in Vienna, Austria.

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

References 

1. Free M, Choi H, Baweja R. Compulsive Biting and chewing with mixed amphetamine salts: a case report. Innov Clin Neurosci. 2024;21(4–6):11–13. 
2. Daigneault S, Braun CM, Montes JL. [Hypothalamic hamartoma: detailed presentation of a case]. Encephale. 1999;25(4):338–344. 
3. Espeche A, Galicchio S, Cersósimo R, et al. Self-limited epilepsy of childhood with affective seizures: a well-defined epileptic syndrome? Epilepsy Behav. 2021;117:107885. 
4. Dickson PR, Lang CG, Hinton SC, et al. Oral stereotypy induced by amphetamine microinjection into striatum: an anatomical mapping study. Neuroscience. 1994;61(1):81–91.