K. Ashley Garling, PharmD

 or toxicity in drug utilization reviews; however, it is often difficult to determine when to counsel a patient versus the need to intervene by contacting the physician. The good news is that serotonin syndrome is thought to be fairly rare. Most reported cases are mild and treatable resolving within a few days, but depending on the offending medications, serotonin syndrome can still occur.

Serotonin syndrome is caused by elevated serotonin in the central and peripheral nervous system that causes a triad of symptoms. The symptoms of serotonin syndrome, which present within hours of ingesting the offending medications, often include autonomic dysfunction, neuromuscular excitation, and altered mental status.

It is important to note that not all symptoms of the triad present simultaneously; however, approximately half of patients present with the autonomic symptoms of diaphoresis and tachycardia.

 Additionally, the most common neuromuscular symptoms include myoclonus and hyperreflexia, whereas the altered mental status typically precipitates as confusion and agitation.

When do we call a physician or refer a patient experiencing symptoms?

The highest risk combinations are often when 2 or more medications, that work by different mechanisms to increase serotonin, are present in the body. This can occur when prescribing a new serotonergic medication, increasing a dose of a medication, or switching medications without an adequate washout period (

). Monoamine oxidase inhibitors (MAOI) and those with similar properties, such as metaxalone, linezolid, and methylene blue, should be avoided with other serotonergic medications due to more associated severe toxicity and fatalities.

If a patient notifies you of spontaneous clonus (involuntary muscle contractions) or new tremor and hyperreflexia (feeling twitchy), this is often a strong indication of serotonin syndrome and immediate referral to emergency services is recommended.

Combinations such as inducible or ocular myoclonus (uncontrollable eye movements) plus agitation or diaphoresis (unusual sweating), hypertonia (stiff muscles) with ocular or inducible clonus plus a temperature over 100 degrees Fahrenheit are also highly selective diagnosis criteria for serotonin syndrome and require immediate referral to emergency services.

After appropriate introductions and identification of the patient, start by reporting to the physician what the patient is currently taking in relation to the interaction concern. This will ensure that the doctor has a complete medication history and cover any unknowns in the medication list; especially if there are multiple providers involved.

Next, explain that the combination of the offending medications may put the patient at risk for serotonin syndrome. Explain the risk of the interaction to the physician (

) and how the symptoms may manifest. Lastly, the most important component of any call to a physician is having an alternative medication choice or a plan for therapy.

Plans for therapy can be as simple as titrating the dose(s) more slowly, using the lowest doses possible, and monitoring for symptoms every 24 to 48 hours.

It's recommended to counsel all patients that are starting or increasing an SSRI, SNRI, MAOI, migraine medication (triptan), pain medication, or anyone who may concurrently take more than 1 serotonergic medication. It is also recommended to ensure patient counseling on certain medication combinations.

Counsel all patients using paroxetine or fluoxetine in combination with tramadol due to long medication half-life, additive serotonergic properties, and inhibition of CYP2D6.

 Additionally, counseling anytime a patient is combining 1 or more opiates; or combining serotonergic medications with those containing tricyclic properties (tricyclic antidepressants, clomipramine, imipramine, cyclobenzaprine, etc.) is supported by literature.

The first step in counseling on serotonin syndrome is to avoid scaring the patient, therefore wording is important (

). It is important to emphasize that cases are rare and symptoms do occur very quickly typically within the first 24 hours to the first few days of use.

Describing the symptoms of serotonin syndrome in simple and plain language is highly recommended. Descriptions such as unusual sweating, fast heart rate, feeling twitchy or experiencing involuntary muscle contractions, having stiff or jerky muscles, changes in vision or uncontrollable eye movements, getting unusually agitated, or feeling confused are all good substitutions for the technical jargon.

During the counseling sessions, inquire about the use of herbal or dietary products, other prescription medications, and any OTC medications. Update all allergies and health conditions in the patient’s profile to ensure that future prescriptions will flag precautions in your software.

Ultimately, the better you know your patients, the more you can prevent medication-related problems. Trust your mental red flags and if you feel uncomfortable with a prescription follow-through, gather more information, and always document your counseling and interventions.

Figure 1. Patient-Centric Counseling Guide

1. Robert ZW, Vishal V, Sukhdeep K,Nathan WH. Serotonin syndrome: Preventing, recognizing, and treating it. 

2. Simon LV, Keenaghan M. Serotonin Syndrome. [Updated 2022 Feb 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK482377/

3. Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. 

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4. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. 

5. Foong AL, Patel T, Kellar J, Grindrod KA. The scoop on serotonin syndrome. 

6. Ables AZ. Prevention, Diagnosis, and Management of Serotonin Syndrome. 

7. Zieve D. Serotonin syndrome: Medlineplus medical encyclopedia. MedlinePlus. https://medlineplus.gov/ency/article/007272.htm. Accessed April 3, 2022.

8. Garling KA. Revitalization of a communication pharmacy course: The journey of reframing student perceptions. 

. 14(2):138-144. https://doi.org/10.1016/j.cptl.2021.12.002.

Articles

The symptoms of serotonin syndrome often include autonomic dysfunction, neuromuscular excitation, and altered mental status.

When to Call, When to Counsel: Serotonin Syndrome

As more medications penetrate the market, pharmacists will need to interpret more drug utilization reviews (DUR). Very commonly seen, high severity drug interaction, include those that result in QT prolongation and torsades de pointes (TdP).

However, you may be asking what is the clinical significance and occurrence of drug-induced QT interval prolongation?

QT prolongation is an extended or abnormal repolarization of the cardiac ventricle that can lead to life-threatening arrhythmias, including torsades de pointes (TdP).

 A QTc greater than 500 ms has been associated with a 2-fold to 3-fold increase in risk for TdP.

Medications are the primary cause of acquired QT-prolongation, although the exact mechanism of why some people evoke TdP but others do not is still unknown. In the United States, 300,000 sudden cardiac deaths occur per year, and although the incidence is largely unknown, TdP probably accounts for fewer than 5%.

Although the incidence of TdP is rare, the severity of the reaction makes QT prolongation a serious concern when prescribing and administering medications.

Contacting the prescribing physician is warranted when patients have moderate to high risk of QT prolongation. Individual risk factors contribute to decision making; however, practitioners should consider compounding factors to actively determine risk (

Patients with low risk include those of older age (>65 years old), female gender, and on a loop diuretic. The risk increases for those that have a history of hemodynamic instability, diagnosis of heart disease, heart failure, myocardial infarction, bradycardia, or a history of arrhythmia.

Be cognizant of patients with recent hospitalization, including surgery, sepsis, and trauma, which can also put them at risk for electrolyte abnormalities. If a patient presents to the pharmacy with potentially cardiac-related symptoms, this is always a situation in which urgent referral is most appropriate.

Patient profile red flags can also be medications indicating gastrointestinal (GI) conditions, diabetes, a history of diarrhea or vomiting, and electrolyte supplementation, such as magnesium and potassium.

 Additional considerations should be noted when patients have conditions that predispose them for electrolyte abnormalities, such as chronic alcohol and substance use, malnutrition, kidney disease, hepatic impairment, lung disease, and cancer, which also may have additional risk factors for QT prolongation.

) should always occur and be thoroughly documented if a physician has approved continuation of dispensing after being called or if a patient is of a low risk for QT prolongation (

Additionally, anyone starting or increasing the dose of a contributing medication (

), having newly diagnosed contributing health conditions (

), or that has a drug-interaction putting them at risk for QT prolongation (

Table 2. QTc prolonging CYP450 Drug Interactions

Medications associated with QT prolongation are antiarrhythmics, antidepressants, antiemetics, antihistamines, antipsychotics, fluoroquinolones, and macrolide antibiotics.

 Keep a watchful eye on drug interactions that may reduce the elimination of QT prolonging agents; mainly CYP 3A4 and 2D6 inhibitors.

Counseling on QT prolongation is a delicate matter to avoid frightening the patient, therefore, using plain language and a sensitive communication approach is necessary. It is recommended to use a counseling technique based on open-ended questions (

) to ensure patient information retention during the counseling session.

A key component to prioritize in this counseling is inquiring into the patient’s medical history, current conditions, and use of additional medications, including herbals, dietary supplements, and OTC medications. When discussing the precautions for the medication(s), inform patients about the more common clinical presentation, including dizziness, palpitations (rapid, irregular, pounding heart beat), and syncope (fainting).

Explain that if the patient experiences any of these signs or symptoms, they should contact their physician and seek immediate medical attention. Lastly explain that this condition is uncommon; however, if additional risk factors for TdP occur (

) to discuss these changes with all health care providers.

K. Ashley Garling, PharmD, clinical assistant professor, The University of Texas at Austin College of Pharmacy.

Raquel T. Khanoyan, PharmD candidate 2022, The University of Texas at Austin College of Pharmacy.

Li M, Ramos LG. Drug-Induced QT Prolongation And Torsades de Pointes. 

Cohagan B. Torsade de Pointes. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK459388/. Published August 11, 2021. Accessed March 7, 2022.

Jatin Dave MD. Torsade de Pointes. Overview, Pathophysiology, Etiology of Torsade. https://emedicine.medscape.com/article/1950863-overview#a3. Published January 12, 2022. Accessed March 7, 2022.

Balcı AK, Koksal O, Kose A, et al. General characteristics of patients with electrolyte imbalance admitted to emergency department. 

. 2013;4(2):113. doi:10.5847/wjem.j.issn.1920-8642.2013.02.005

Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention, and management. 

Viera AJ. Potassium Disorders: Hypokalemia and Hyperkalemia. 

Treatment of a heart attack. www.heart.org. https://www.heart.org/en/health-topics/heart-attack/treatment-of-a-heart-attack. Published June 10, 2021. Accessed March 21, 2022.

Medications used to treat heart failure. www.heart.org. https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/medications-used-to-treat-heart-failure. Published May 31, 2017. Accessed March 7, 2022.

Garling KA. Revitalization of a communication pharmacy course: The journey of reframing student perceptions. 

Medications are the primary cause of acquired QT-prolongation, although the exact mechanism of why some people evoke torsades de pointes but others do not is still unknown.

When to Call, When to Counsel:  QT Interval Prolongation Drug Interactions

Pharmacists and pharmacies are on the frontline of vaccinating citizens of the United States with the COVID-19 vaccines.

 With this unique opportunity, pharmacists are in a position to change public perception of the pharmacy profession as a whole, in addition to increasing their own pharmacy’s reputation in the community by optimizing patient’s immunization experience.

Studies have shown that one of the best ways to improve a patient’s experience is by engaging with good communication skills.

 The Center for Advancement of Pharmacy Education Educational Outcomes 2013

 and the Accreditation Council for Pharmacy Education

 have also identified the public health need for improved communication for pharmacists.

Communication skills such as self-awareness, building rapport, impression management, audience-focused messaging, reflective listening, and using inclusive stigma-free language are a top priority for patients.

The initial steps to optimizing a patient’s immunization experiences are immersed in the patient’s perception of your overall pharmacy. For a positive perception, ensure you have a good workflow with your staff, place employees in tasks that are based on their strengths and knowledge base, and know your eligibility to administer vaccines.

Being efficient with a dedicated and reliable pharmacy team safeguards you and your pharmacy’s reputation. Also, be prepared with an emergency plan or back-up staff positions to accommodate for breaks, illness, and absence of members of the pharmacy team to keep operations running smoothly.

The next step is ensuring you and your staff are using good communication skills. In good communication, self-awareness is a key component in the construct of resilience among health care providers.

In health care’s busy multitasking atmosphere, it is easy to forget that verbal and nonverbal communication is crucial impression management (Millie A. Harrison, 2018). Nonverbal communication includes body language, which encompasses everything from posture to use of personal space.

Utilizing S.U.R.E.T.Y (T., 2011) can help keep a positive and open body language by: 

our Intuition. The use of face masks also increases the need for maximizing body language and verbal communication.

When speaking, always remember the voice carries a lot of emotion and can change the interpretation based on tone or pitch, cadence or rate, and volume. Tone or pitch can convey meaning or intensity of the message while cadence or rate, and volume can lead to a variety of emotional implications (Brommel, 1972).

Immunizing patients is an excellent way to build rapport, engage patients, learn more about their medical history, and to ultimately educate patients on their health and what pharmacists can do to make a difference. While you are preparing for administration, try using the vaccination prime questions (

), augmented from the original 3 prime questions of the Indian Health Services counseling technique to elicit a counseling session about the vaccine.

These questions serve as a framework or lead to further discuss other required and recommended counseling points.

 While using these questions and counseling points, try to focus on giving an audience-centered message while using reflective listening to tailor the conversation to the patient and display empathy.

Audience-centered messaging evaluates the patient to determine the content and language usage needed to have the most effective communication (Lombardo, 2014). Reflective listening re-states or reflects what the patient expressed so they can hear it in a new way and know the immunizer is actively engaged in the conversation (Katz & McNult, 1994).

Language Etiquettes To Utilize While Immunizing

Language etiquette in health care is when a provider shows consideration for a patient by using preferred terms to reduce stigma and improve the patient’s perceptions.

 When thinking of preferred terms, use simple terms and practice plain language in lieu of clinical or medical terminology to ensure clarity and understanding of the patient. 

Plain language removes jargon, acronyms, abbreviations, and any other technical terms that may be less known outside of a health care field (The Plain Language Action and Information Network, 2011).

Whenever potentially sensitive topics arise in a patient discussion, the use of language etiquette will help keep the conversation comfortable and open. Language etiquette is available for discussing mental health, suicide, substance use, HIV, age, weight, sexual orientation, grief, and many other topics.

An integral part of any language etiquette in sensitive subjects centers around utilizing person-first language. During an immunization person-first language, such as “Susan, are you living with HIV?” or “Jackson, have you experienced any conditions that could involve your immune system like cancer?” This approach can help reduce stigma by not defining the patient by their condition.

Choosing sensitive terminology, such as “John, since you experience allergies, have you ever had a reaction to a vaccine?” or sensitive question framing, such as “For the purpose of the vaccine, are you looking to become pregnant, are pregnant, or breastfeeding at this time?”

Framing questions in a sensitive and inclusive manner while using person-first language can lead to not only an optimal experience for a patient but a rewarding experience for the practitioner.

Along with preferred etiquette, phrasing, and terminology, further tailor your language and use other inclusive questions to improve the patient’s experience. Adding questions such as “How would you like to be addressed?” and “Do you have any lifestyle, work-related, or religious observances coming up that we need to keep in mind?’” (

Allow patients to express their individual needs and inclinations.

Asking a patient how they would like to be addressed is great for eliciting preferred names, titles, and pronouns from your patients. The second question can cover any topics such as exercise, social events, job-related tasks, and personal beliefs that are always beneficial to know when practicing patient-centered care.

Communication is the key when trying to optimize a patient’s immunization experience and shape the public’s opinion of the profession of pharmacy. Using the vaccination opportunity to get to know more about your patients by discussing their lifestyles, allergies, and conditions can aid not only in upcoming discussions, but also assist in health care situations with that patient in the future.

Utilizing inclusive questions, preferred terms, and language etiquette can turn the simple task of immunizing into a fulfilling patient-centered opportunity for both pharmacists and patients. The COVID-19 pandemic is not only giving pharmacists the opportunity to help protect our patients, but it is giving us the opportunity to communicate what a large impact pharmacists can make in the world.

Ryan Hoffart, Doctor of Pharmacy Candidate 2023, contributed to this article.

Op-Ed Project National Public Voices Fellow

The University of Texas at Austin College of Pharmacy

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Using inclusive questions, preferred terms, and language etiquette can turn the simple task of immunizing into a fulfilling patient-centered opportunity for both pharmacists and patients. 