Serotonin Syndrome Due to an Overdose of Moclobemide and Venlafaxine

Serotonin is a neurotransmitter produced in presynaptic neurons by hydroxylation and decarboxylation of the dietary amino acid L-tryptophan. After neuronal stimulation, serotonin is released into the intrasynaptic space where serotonin binds to postsynaptic receptors to effect neurotransmission. Presynaptic serotonin receptors function as a feedback loop to inhibit additional release. A reuptake mechanism returns serotonin to the cytoplasm of the presynaptic neuron where it is inactivated by monoamine oxidase.

Serotonin Syndrome

Serotonin syndrome (SS) is the result of an excess of serotonin linked to taking substances which increase the quantity of serotonin in the central nervous system (CNS). It was demonstrated in animals that, in the SS, the level of extracellular serotonin was at least 10-fold greater than the basal level. This excess of serotonin leads to an overstimulation of postsynaptic receptors in the CNS, mainly of the 5-HT1A receptors, associated with hyperactivity, hyperreflexia  and anxiety, and the 5-HT2A type, associated with hyperthermia, incoordination and neuromuscular excitement .

The SS can be caused by taking an excessive quantity of just one medicine, or more often, following the simultaneous ingestion of several drugs which synergistically increase the synaptic serotonin quantity. SS can also arise when successively taking two serotonergic drugs with an insufficiently long treatment-free interval. The majority of products concerned are antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), non-selective inhibitors, such as serotonin–norepinephrin reuptake inhibitors (SNRI), monoamine oxidase inhibitors (MAOIs), but there are also opiates and substances classed as narcotics such as cocaine and LSD. The diagnosis of SS depends on clinical signs which combine consciousness disturbances, neuromuscular tone abnormalities and autonomic hyperactivity (tremor, agitation, hypertension, cardiac rhythm disorders). The presentation of SS ranges from mild symptoms to life-threatening cases where patients need to be admitted to hospital and receive appropriate care. Diagnosis criteria were proposed by several authors. The Sternbach’s criteria were modified by Radomski et al. In 2003, Dunkley et al proposed more simple criteria to evaluate serotonin toxicity. A guideline intended for health professionals, for appropriate out-of-hospital triage and initial management in patients with a suspected ingestion of SSRIs was published in 2007 by Nelson et al.

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