Introduction
Selective serotonin reuptake inhibitors (SSRIs) are the recommended first-line treatment for depression. However, other classes of medications such as monoamine oxidase inhibitors are also used. These drugs alter the levels of the neurotransmitter serotonin and are associated with the occurrence of an adverse effect known as serotonin syndrome or serotonin toxicity (Wang et al., 2016). This paper reviews the article “serotonin syndrome” by Buckley et al. (2014) and describes the occurrence of serotonin syndrome, its symptoms, how a provider can diagnose the disorder in patients, treatment options, and the prevention of serotonin toxicity.
Serotonin Syndrome
Serotonin syndrome is a drug-generated condition associated with elevated concentrations of serotonin in the central nervous system. The occurrence of serotonin syndrome is linked to the use of serotonergic drugs, which are medications that affect the production and working of serotonin. Nonetheless, severe toxicity happens only when two or more serotonergic drugs, one being a monoamine oxidase inhibitor, are used simultaneously (Buckley et al., 2014). Moderate toxicity is documented in the overdose of one drug that exceeds the therapeutic measure and is common in 15% of treatments with SSRIs (Buckley et al., 2014; Scotton et al., 2019).
Signs of Serotonin Syndrome
The archetypal triad of the clinical signs of serotonin toxicity includes neuromuscular excitation, dysfunction of the autonomic nervous system, and changes in mental state. Signs of neuromuscular excitation include rigidity of muscles, overactive reflexes, and clonus, which refers to rhythmic involuntary contractions of muscles (Wang et al., 2016). The most common form of clonus is ocular, which comprises changes in eye gaze. Conversely, indications of autonomic nervous system excitation include a fast heart rate and elevated body temperatures. Agitation and confusion are the hallmarks of a distorted mental state. Serotonin toxicity begins within hours of taking medications that raise the levels of serotonin. Other symptoms that may be present in mild toxicity include nervousness, insomnia, diarrhea, enlarged pupils, and tremors (Foong et al., 2018). Severe toxicity may result in rhabdomyolysis and death. The onset of symptoms is critical to the differentiation of serotonin syndrome and neuroleptic malignant syndrome, which has a slow onset of several days. Furthermore, neuroleptic malignant syndrome presents with rigidity and extrapyramidal symptoms but does not feature clonus.
Diagnosing Serotonin Toxicity
A provider can diagnose serotonin toxicity by observing the presence of symptoms such as neuromuscular excitation, dysfunction of the autonomic nervous system, and changes in mental state. During the assessment, the first step is evaluating all medications being taken by the patient, including prescription medications, over-the-counter drugs, natural supplements, and illicit drugs. The clinician should also determine whether the patient suffers from other conditions such as encephalitis and convulsive seizures. The provider needs to find out whether the patient is using stimulants such as cocaine, ecstasy, cathinone, and amphetamines as well as herbal regimens such as ginseng and St John’s wort (Foong et al., 2018). Certain medications such as fentanyl, tramadol, methylene blue, antiemetics, antiepileptics, and linezolid can result in the above symptoms (Wang et al., 2016). The presence of a potentially serotonergic drug in the patient’s medication list is indicative of serotonin syndrome.
After ascertaining the current medications, a clinician should then eliminate the probability of other conditions such as alcohol or drug withdrawal, antidepressant withdrawal, anticholinergic toxicity, meningitis, malignant hyperthermia, and neuroleptic malignant disorder. Before diagnosing serotonin syndrome, the clinician should ensure that the patient presents with the classical symptoms of the disorder, which make up the Hunter serotonin toxicity criteria (Werneke et al., 2019), a certified benchmark for the diagnosis of serotonin toxicity.
Treatment of Serotonin Syndrome
Most cases of serotonin syndrome do not need medications because they resolve by cutting down the drug dosage or stopping the medication. The symptoms of mild to moderate serotonin syndrome often end within one to three days after discontinuing the serotonergic medication. However, severe toxicity is considered a medical emergency because it can be aggravated by serious hyperthermia, intravascular coagulation, rhabdomyolysis, and respiratory distress syndrome. Therefore, it is treated by providing serious supportive care (Wang et al., 2016; Scotton et al., 2019). Supportive care mainly involves sedation, providing adequate hydration, and monitoring of urine output and vital signs such as pulse, temperature, and blood pressure. Sedation helps to minimize muscle hyperactivity and may involve the administration of oral diazepam or midazolam infusion (Buckley et al., 2014). Active cooling using ice packs, water sprays, or cooing blankets may be needed in severe cases to preclude hyperthermia and consequent organ failure.
Preventing Serotonin Syndrome
Serious serotonin syndrome can be prevented by avoiding lethal drug interactions, for example, between SSRIs and monoamine oxidase inhibitors. Washout periods, which are durations of no medical treatment, should be followed when substituting antidepressants (Buckley et al., 2014). Clinicians should avoid prescribing serotonergic medications for non-psychiatric disorders, for example, tramadol for pain relief. Patients should be informed about possible drug interactions, particularly those involving over-the-counter medications and herbal remedies with serotonergic activity. The lowest effective dose of antidepressants should also be used to avoid overdoses. Clinicians should also make follow-ups within one to two days of initiating a new medication or increasing the dosage.
Conclusion
Serotonin syndrome is an avoidable adverse effect of interactions between serotonergic medications, which is attributed to disruptions in the levels of the neurotransmitter serotonin. This condition presents three unique features of changes in mental status, neuromuscular excitation, and dysfunction of the autonomic nervous system. Its treatment involves discontinuing causative mediation and managing severe effects through supportive care. Knowledge of drugs with strong serotonergic effects is necessary to avoid drug interactions.
References
Buckley, N. A., Dawson, A. H., & Isbister, G. K. (2014). Serotonin syndrome.BMJ, 348, 1-4. Web.
Foong, A. L., Grindrod, K. A., Patel, T., & Kellar, J. (2018). Demystifying serotonin syndrome (or serotonin toxicity). Canadian Family Physician, 64(10), 720-727.
Scotton, W. J., Hill, L. J., Williams, A. C., & Barnes, N. M. (2019). Serotonin syndrome: Pathophysiology, clinical features, management, and potential future directions. International Journal of Tryptophan Research, 12, 1-14. Web.
Wang, R. Z., Vashistha, V., Kaur, S., & Houchens, N. W. (2016). Serotonin syndrome: Preventing, recognizing, and treating it.Cleveland Clinic Journal of Medicine, 83(11), 810-817. Web.
Werneke, U., Jamshidi, F., Taylor, D. M., & Ott, M. (2016). Conundrums in neurology: Diagnosing serotonin syndrome–A meta-analysis of cases.BMC Neurology, 16(1), 1-9. Web.