Beware of serotonin syndrome during the COVID-19 pandemic

To the Editor

During the COVID-19 pandemic, patients with unknown fever require a careful differential diagnosis, and serotonin syndrome is one of the differential diseases in febrile patients taking antidepressants.

A 74-year-old man developed depression last year and was in remission with fluvoxamine 150 mg/day. However, anorexia with tremor of the lower limbs appeared, which was diagnosed as an exacerbation of depression, and mirtazapine 30 mg/day was additionally administered. Two days later, high fever, anosmia and convulsions in the lower limbs appeared, and the patient was brought to our emergency room on suspicion of COVID-19. On arrival, his temperature was 38.9°C, blood pressure 170/90 mm Hg, and he had tachycardia and sweating. Hyperreflexia in the lower extremities was noted, but head computed tomography (CT) showed no obvious lesions, and repeated polymerase chain reaction (PCR) tests for COVID-19 were performed, all of which were negative. The patient was diagnosed as having serotonin syndrome according to the Hunter criteria (Dunkley et al., 2003), and all medications were discontinued and intravenous infusions were administered. A few days after discontinuation of antidepressants, tremor disappeared and body temperature became normal. Appetite and sense of smell recovered within a month after discontinuation of antidepressants, and a score of 5 on the Naranjo scale suggested the possibility of a relationship between serotonergic drugs and this adverse reaction. The patient’s family gave permission for the presentation.

During the COVID-19 pandemic, fever, general malaise and olfactory disturbances should be considered COVID-19 infection. However, when increasing serotonergic agents, the possibility of serotonin syndrome should be considered (Silins et al., 2007). The diagnosis of serotonin syndrome is difficult, but one of the key diagnostic features is tremor with hyperreflexia. Serotonin regulates a variety of physiological functions, including food intake, reward, reproduction, sleep–wake cycle, memory, cognition, emotion and mood. Therefore, there is a danger that an excess of serotonin will alter all of these functions. The anorexia and decreased odor in the present case may be due to excess serotonergic neurotransmission rather than depression or COVID-19 symptoms. The serotonin controls the appetite center, so excess serotonin decreases appetite. Although there are no reports of transient olfactory loss in serotonin syndrome, the olfactory bulb is regulated by serotonergic neurotransmission with adult neurogenesis throughout life (Fomin-Thunemann and Garaschuk, 2022). Excess serotonin affects the neurogenesis of the olfactory bulb and may cause transient olfactory abnormalities.

In conclusion, serotonin syndrome is also similar to the symptoms of COVID-19 and requires careful differential diagnosis in this pandemic situation.