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

Dear Editor:

We greatly appreciate the letter to the editor regarding the article “Compulsive Biting and Chewing with Mixed Amphetamine Salts: A Case Report” by Free et al,¹ as it provides an excellent framework for further discussion on this interesting case study. 

This case involved a 32-year-old female patient with no prior neurological history. There was a temporal association between the onset of symptoms and the initiation of the medication, and the symptoms resolved completely upon initial discontinuation. There were no consistent or concerning neurological signs observed at the time, which is why an acute workup was not pursued. However, we fully agree with your point—if symptoms were to persist or recur, an organic workup would absolutely be warranted. Your recommendations for further analysis in such situations are well taken.

Reviewing the timeline in this study, we recognize that as a case study in a clinical setting, we relied on the patient to best report the timeline and onset of potential side effects and benefits when starting a new medication. The best clarification of timeline per the patient’s recollection and clinical documentation is as follows: MAS IR 2.5mg daily was started for approximately four days and then increased to 5mg daily. Once increased to 5mg daily, the urge to bite and chew occurred within 1 to 2 hours, and then the effect persisted for 1 to 2 hours. MAS IR was reduced to 2.5mg the following day, and symptoms improved. A “few” days later, as reported by the patient, she again increased MAS IR to 5mg daily. The urge to chew and bite recurred. She then continued the medication dose daily at the same time each morning, and the urge to chew and bite subsided after one week of consistent use. 

Notably, while we must consider other medication interactions, such as lamotrigine, we identified that no other changes to the medication regimen were made during this time, and the urge to chew and bite subsided after one week of consistent MAS use. This might suggest a potential medication interaction contributing to the compulsive chewing is less likely, but again, it is a valid point to consider. Regarding the animal study you shared, we sincerely appreciate your input. It provided valuable insight and added depth to the discussion.

Additionally, we agree that it was perplexing that the patient initially did not tolerate MAS IR 5mg, but previously tolerated MAS XR 10mg daily and eventually tolerated MAS IR 5mg daily after one week of consistent use. We proposed that the patient had side effects during periods with more fluctuations in plasma concentration and with more rapid increases in plasma concentration. The time to side effect onset and duration of side effect burden correlated with the time peak plasma concentration of the MAS IR, which is reached more rapidly with IR as compared to XR formulations.^1,2 MAS IR has a half-life of approximately 9.77 to 13.8 hours.³ After approximately five half-lives (2–3 days) of consistent dosing of MAS IR, the medication should reach a steady state. We proposed that once in steady state, there might be less fluctuation in plasma concentration, which could provide an explanation for fewer side effects over time.

Once again, thank you for engaging in this meaningful exchange of ideas. We believe this offers a well-rounded perspective on the neuropsychiatric complications potentially associated with such presentations, as well as the importance of continuing to evaluate for possible organic etiologies, as you thoughtfully outlined in your letter.

With regards,

Melissa Free, MD; Hena Choi, BA; and Ritika Baweja, MD

Dr. Free is with Penn State Health College of Medicine and Pennsylvania Psychiatric Institute in Hershey, Pennsylvania. Ms. Choi was most recently with Penn State College of Medicine in Hershey, Pennsylvania. Dr. Baweja is with Penn State Health College of Medicine in Hershey, PA.

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. Tulloch SJ, Zhang Y, McLean A, Wolf KN. SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration. Pharmacotherapy. 2002;22(11):1405–1415. 
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/011522s045lbl.pdf Teva Pharmaceuticals. Adderall [package insert]. US Food and Drug Administration. Revised Oct 2023. Accessed 5 Nov 2023.