Bowdoin Science Journal

Martina Tognato Guaqueta

POTS vs Atomoxetine: The Unseen Interaction

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Postural Orthostatic Tachycardia Syndrome (POTS) is a malfunction in the body’s autonomic nervous system. Rather than the blood vessels below their heart compensating by constricting, when a person with POTS goes from a lying to a standing position, a large amount of blood pools in the legs and abdomen. Normally, the blood vessels in the lower extremities constrict to maintain appropriate blood pressure throughout the whole body and help return the blood to the heart and head. The autonomic system (the part of the nervous system that is in charge of the involuntary aspects of the body) responds to low blood pressure by releasing norepinephrine and adrenaline, which cause vasoconstriction and a rise in heart rate. In POTS patients, vessels do not respond to the hormones and remain vasodilated. This combination of high heart rate and insufficient blood flow to the brain causes characteristic dizziness, fainting, and fatigue. POTS can be aggravated by a variety of things, including strenuous exercise, caffeine, hot environments, and certain medications (POTS, n.d.). 

One such class of medications is norepinephrine reuptake inhibitors (NOIs). Used to treat ADHD, major depressive disorder, and narcolepsy, NOIs block the uptake of norepinephrine in the synapses (De Crescenzo et al., 2018). This type of medication allows norepinephrine to stay in the blood longer, elevating mood and energy levels and enhancing focus. A common side effect is an elevated heart rate, which aggravates POTS. 

Green et al. conducted the first study examining the acute effects of atomoxetine on POTS patients. The study was composed of 27 patients and a variety of tests. A baseline was created to manage the patients’ diets. This entailed removing methylxanthines from their diet, which includes caffeine among other compounds, and moderating sodium and potassium intake. Additionally, all long-term medications were suspended for at least 5 half-life periods to ensure no hormonal effects would be present. All of these measures were taken to minimize the exacerbation of POTS symptoms (Green et al., 2013). 

All patients received the atomoxetine and the placebo (on different days). During this time, a posture study was done. Measurements of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and plasma catecholamines were taken during a lying position and a standing position. This targets the effects of POTS, highlighting the possible impact of the atomoxetine. 

The posture study was paired with the medication study. During the medication study, patients were asked to fill out a symptom feedback form before the experiment, and every hour up to 4 hours after drug administration. This is because peak atomoxetine concentration occurs 1-2 hrs after ingestion. The Vanderbilt Orthostatic Symptom Score (VOSS) was used on the symptom feedback form, where patients are asked to rank the following on a scale from 1-10: mental clouding, brain fog, shortness of breath, palpitations, tremors, headache, tightness in the chest, blurred vision, and nausea. The lowest (1) is no symptom burden, and 10 is the worst. 

Researchers found that when patients took atomoxetine, their symptom burden increased. This presented a statistically significant increase in heart rate and a general upward trend in blood pressure throughout the 4 hours. In the case of the placebo, there was a decrease in symptom burden as the 4-hour period progressed. 

Atomoxetine is a non-stimulant medication used to treat ADHD; unfortunately, the stimulant alternatives are found to have similar effects on POTS patients. Due to a susceptibility to heart rate changes, ADHD medication negatively interacts with the condition and must be administered with exceeding caution. This interaction is important for prescribing professionals to be aware of. As this is a relatively under-researched intersection, consideration of mechanisms and close patient-doctor communication is necessary when considering medication. 

Figure 1: Results of VOSS with and without atomoxetine (Green et al., 2013)

Graph describing the effects of the medication on POTS symptoms

References

De Crescenzo, F., Ziganshina, L. E., Yudina, E. V., Kaplan, Y. C., Ciabattini, M., Wei, Y., & Hoyle, C. H. (2018). Noradrenaline reuptake inhibitors (NRIs) for attention deficit hyperactivity disorder (ADHD) in adults. The Cochrane Database of Systematic Reviews, 2018(6), CD013044. https://doi.org/10.1002/14651858.CD013044

Green, E. A., Raj, V., Shibao, C. A., Biaggioni, I., Black, B. K., Dupont, W. D., Robertson, D., & Raj, S. R. (2013). Effects of norepinephrine reuptake inhibition on postural tachycardia syndrome. Journal of the American Heart Association, 2(5), e000395. https://doi.org/10.1161/JAHA.113.000395

POTS: Causes, Symptoms, Diagnosis & Treatment. (n.d.). Cleveland Clinic. Retrieved April 8, 2025, from https://my.clevelandclinic.org/health/diseases/16560-postural-orthostatic-tachycardia-syndrome-pots

 

TMJ Arthroscopy: How well does it work in Ehlers Danlos patients?

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The temporomandibular joint (TMJ) is responsible for the mandible’s chewing, talking, and all movement. As a condylar joint, this joint allows motion in two planes: side to side and up and down. A disc cushions the bone to facilitate this motion and serves as a lubricant. 

 

Figure 1: TMJ diagram (TMJ Disorders – Symptoms and Causes, n.d.).

 Temporomandibular disorders (TMD) often arise from damage or irritation relating to the disc. To determine the condition of the joint, physicians use the Wilkes scale, which allows for the assessment of internal derangement/damage of the TMJ. TMD is often a symptom of a larger condition, it can arise from connective tissue disorders, injury, teeth grinding, etc.

 

Figure 2: Wilkes Scale descriptive table (Table 1 . Wilkes Classification of TMJ Internal Derangement, n.d.)

 

 

A patient’s placement on this scale indicates the type of treatment they could be a candidate for.  This could range from over-the-counter medications to physical therapy, to Botox injections, and a variety of surgeries. A surgery often seen is a TMJ arthroscopy.  The arthroscopic element refers to the minimally invasive approach assisted by a camera called an arthroscope. Done under general anesthesia, a surgeon will enter the joint space through a small incision. The image of the joint is delivered to a screen through an arthroscope. During the procedure, the surgeon may reposition the disc, flush the joint, and remove scar tissue to alleviate pain (Arthroscopy for Temporomandibular Disorders (TMDs) | Kaiser Permanente, n.d.). This, however, is not the only option, and can only be decided upon looking at the full picture of a patient’s history—for example, a connective tissue disorder. 

Ehlers-Danlos (EDS) is a group of connective tissue disorders that can affect many systems, including the joints and, in turn, the TMJ.  Within the group, each particular variation has a different set of symptoms. For example, vascular EDS causes the blood vessels to rupture, whereas hypermobile EDS (hEDS) causes frequent joint dislocations. Some types of EDS have a clear genetic link, however, the origins of hEDS have yet to be understood. Due to the overly flexible nature of their joints, hEDS patients often encounter issues with their TMJ.  (Ehlers-Danlos Syndrome – Symptoms and Causes, n.d.).

Jerjes et al. conducted a retrospective case study that looked at the outcomes of 18 hEDS patients who underwent arthroscopic surgery to treat their TMDs. All patients were female and between the ages of 23-60 years old. Due to the EDS, TMJ dislocation was a common history within the sample. In turn, the dislocations were linked to the damage and pain, which were visualized during the arthroscopies. This demonstrated a link between the state on the TMJ and hEDS status. Moreover, 12 out of the 18 experienced TMD bilaterally, meaning there was pain on both sides (Jerjes et al., 2010). 

Furthermore, it seemed as though the intervention was most commonly done at/by the Wilkes Stage III (9 patients at Stage III and 5 at Stage II ). As seen in Figure 2, Stage III is characterized by moderate disc deformity and frequent pain/dislocations.  As the Wilkes Scale goes on, the condition becomes more painful and harder to treat. However, although minimally invasive, arthroscopy is considered a more extreme treatment for TMJ. Over the years, the procedure has developed and improved, reaching an 80-90% success rate (Insel et al., 2020). Despite this, the National Institute of Dental and Craniofacial Research brochure still has a negative outlook on the surgical route as a treatment for TMDs (Jerjes et al., 2010). 

Notwithstanding the controversy, Jerjes et al. demonstrate positive post-operative results. The pain subsided quickly (within 1 week post-operative) for 15 out of 18 patients and 5-6 weeks for the remaining 3. Delayed healing occurred in 4 out of 18 patients. Slow healing is a characteristic of hEDS and could be a potential reason in this case for the post-surgical complication. Most importantly, the mouth opening measured 6 months postoperatively increased from an average of approximately 23-28 mm,  with all final postoperative results being positive. 

Overall, the study aims to illustrate the success of TMJ arthroscopy in hEDS patients and suggests it as the first consideration for invasive procedures. Due to hEDS patients often having a difficult time with wound healing, a minimally invasive procedure is favored. Additionally, these patients have previously sought out other forms of treatment before surgery. This study does not suggest that surgery should be an initial consideration, but it should not be forgotten as an option. 

 

Figure 3: Outside view of an TMJ arthroscopy 

Figure 4: Internal photo is TMJ arthroscopy

 

The hEDS population is small; therefore, studies that center on them and how treatments interact with their condition are few and far between. Moreover, providers for TMJ-related surgeries are scarce. In turn, this middle ground (as noted by Jerjes et al. ) is a neglected area of research. Further development would focus on EDS patients more and seek to understand the interconnectedness of EDS and joint pain and how it can impact the choice of treatments. 

 

References

Arthroscopy for Temporomandibular Disorders (TMDs) | Kaiser Permanente. (n.d.). Retrieved April 8, 2025, from https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.arthroscopy-for-temporomandibular-disorders-tmds.hw209368

Ehlers-Danlos syndrome—Symptoms and causes. (n.d.). Mayo Clinic. Retrieved April 8, 2025, from https://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/symptoms-causes/syc-20362125

Insel, O., Glickman, A., Reeve, G., Kahan, B., Tran, T., & Israel, H. (2020). New criteria demonstrate successful outcomes following temporomandibular joint (TMJ) arthroscopy. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 130(1), e20–e21. https://doi.org/10.1016/j.oooo.2019.12.022

Jerjes, W., Upile, T., Shah, P., Abbas, S., Vincent, A., & Hopper, C. (2010). TMJ arthroscopy in patients with Ehlers Danlos syndrome: Case series. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 110(2), e12–e20. https://doi.org/10.1016/j.tripleo.2010.03.024

Table 1. Wilkes classification of TMJ internal derangement. (n.d.). ResearchGate. Retrieved April 8, 2025, from https://www.researchgate.net/figure/Wilkes-classification-of-TMJ-internal-derangement_tbl1_7691660

TMJ disorders—Symptoms and causes. (n.d.). Mayo Clinic. Retrieved April 8, 2025, from https://www.mayoclinic.org/diseases-conditions/tmj/symptoms-causes/syc-20350941

Top Five Fun Facts About The TMJ. (2022, July 14). Ladner Village Physiotherapy | Delta BC. https://ladnervillagephysio.com/blog/top-five-fun-facts-about-the-tmj

 

Asthma and ADHD: How do Pediatricians Approach This Intersection?

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According to the CDC, 11.4% of children aged 3-17 in the USA are diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) (Data and Statistics on ADHD | Attention-Deficit / Hyperactivity Disorder (ADHD), 2024). ADHD is a developmental disorder characterized by symptoms of hyperactivity, impulsivity, and inattention, as the name suggests. Treating this disorder often requires a variety of approaches including medication, psychotherapy, and workplace or school-based accommodations (Attention-Deficit/Hyperactivity Disorder – National Institute of Mental Health (NIMH), n.d.).  Comorbidities are very common in people with ADHD, this makes it so that it is rarely the only concern during a primary care visit (Silver, 2024). Sleath et al. discuss the communication primary physicians held with families with children that have both ADHD and asthma. There has been found to be a correlation between the severity of ADHD and asthma symptoms (Blackman & Gurka, 2007). In turn, balancing treatment for both primary care visits was a driver for the paper. Asthma is a chronic lung condition that results in the narrowing of the lung pathways. Medication to alleviate symptoms of both ADHD and asthma is often prescribed at primary care visits hence the study of their intersection. 

Figure 1. Happy little girl and pediatrician doing high five after medical checkup. AAP Schedule of Well-Child Care Visits. (2023). Healthy Children.org. https://www.healthychildren.org/English/family-life/health-management/Pages/Well-Child-Care-A-Check-Up-for-Success.aspx

Sleath et al. approach this balance by studying the communication between patients with ADHD and asthma and pediatricians. The study focuses on the communication breakdown when the patient has ADHD during an asthma visit. All of these were pediatric visits. To measure the effectiveness of communication, the American Association of Pediatrics (AAP) guidelines for discussing ADHD were used. The percentage of adherence was measured through the visits using recordings. 

Before data collection eligibility tests were conducted. This made sure that all participants in the study were 8-16 years of age, could speak English, was capable of filling out an assent form, had had at least one prior visit to the clinic, had persistent asthma, and had a guardian present who is over the age of 18 and is competent in English. After the visits concluded, guardians were provided with questionnaires, and children were interviewed. These were used to supplement the recordings. 

The audio taping and coding are the backbone of the data. The audio tapes were transcribed by a coding tool that was flagged for AAP guidelines. To ensure accuracy two research assistants met twice a month to review and refine criteria. The other important aspect of the collection was a thorough socio-demographic data set: gender, age, race, insurance, and tears of asthma. All demographic data but asthma status was also recorded from guardians. 

The results yielded from this were extreme. Throughout the visits 23% of the 296 children had ADHD noted in their medical chart. It was found that boys were more likely to have ADHD diagnoses. It is important to note that it is not because ADHD affects males more, but women are less likely to get diagnosed or are diagnosed later in life due to inattentive presentations (Attoe & Climie, 2023). When understanding the extent of utilization of AAP guidelines, categories were formed; functioning, outcomes, treatment plan, ADHD asthma relationship, chronic and follow-up visits. In all of these categories, the percentage of providers that used AAP guidelines never rose above 40%. In the adherence to medication, only one provider out of the 35 discusses the topic (41 providers participated, but recording forms only 35 were usable). Overall, it was shown that AAP guidelines were more likely to be followed if the visit was unrelated to asthma, highlighting providers’ tendency to neglect proper ADHD management in patients with comorbidities. 

The aim was to highlight the need for better communication practices in the pediatric setting. Particularly in cases where comorbid conditions are present. Future development in this field would be understanding the reason behind the present communication pattern. Approaching the issue from the physician and patient perspective. On the other hand, research on how to remedy the disparity in guideline adherence. 

 

Article based on ‘Communication about ADHD and its treatment during pediatric asthma visits’

Sleath, B., Sulzer, S. H., Carpenter, D. M., Slota, C., Gillette, C., Sayner, R., Davis, S., & Sandler, A. (2014, Feb). Communication about ADHD and its treatment during pediatric asthma visits. Community Ment Health J ., 50(2), 185-192. 10.1007/s10597-013-9678-3

References

AAP Schedule of Well-Child Care Visits. (2023). Healthy Children.org. https://www.healthychildren.org/English/family-life/health-management/Pages/Well-Child-Care-A-Check-Up-for-Success.aspx

Attention-Deficit/Hyperactivity Disorder – National Institute of Mental Health (NIMH). (n.d.). National Institute of Mental Health. Retrieved November 1, 2024, from https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd

Attoe, D. E., & Climie, E. A. (2023, March 30). Miss. Diagnosis: A Systematic Review of ADHD in Adult Women. J Atten Disord, 27(7), 645–657. 10.1177/10870547231161533

Blackman, J. A., & Gurka, M. J. (2007). Developmental and Behavioral Comorbidities of Asthma in Children. Journal of Developmental & Behavioral Pediatrics, 28(2), 92-99. 10.1097/01.DBP.0000267557.80834.e

Data and Statistics on ADHD | Attention-Deficit / Hyperactivity Disorder (ADHD). (2024, May 22). CDC. Retrieved November 1, 2024, from https://www.cdc.gov/adhd/data/index.html

Silver, L. (2024, April 3). ADHD Symptoms Or ADHD Comorbidity? Diagnosing Related Conditions. ADDitude. Retrieved November 1, 2024, from https://www.additudemag.com/when-its-not-just-adhd/

Sleath, B., Sulzer, S. H., Carpenter, D. M., Slota, C., Gillette, C., Sayner, R., Davis, S., & Sandler, A. (2014, Feb). Communication about ADHD and its treatment during pediatric asthma visits. Community Ment Health J ., 50(2), 185-192. 10.1007/s10597-013-9678-3