5-HT syndrome is a potentially life-threatening complication resulting from the use of two or more 5HTergic drugs. It is mostly seen clinically when tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAIO) are combined, but with the widespread clinical use of SSRI antidepressants, there has been increasing interest in the relationship between them and SSRIs. Wang Biao, Department of Psychiatry, Shanghai Mental Health Center The incidence of 5-HT syndrome: There are no reports about it, mostly reported in various cases, which may be due to the fact that 5-HT syndrome is not yet recognized by everyone, in which it may also be confused with malignant syndrome. Pathogenesis: It is believed that the occurrence of 5-HT syndrome may be caused by two or more 5HTergic drugs, for which the following table is given as a hint. Pathogenesis: Under normal conditions, 5HT is released from presynaptic neurons, stimulates postsynaptic receptors, and is then transported from the synaptic gap back to the presynaptic neuron by active operation (or reuptake), where it is “repackaged” or destroyed by monoamine oxidase (MAO). When SSRIs and MAOIs are combined, the SSRI blocks the reabsorption of 5HT and the MAOI inhibits the degradation of 5HT, leaving no escape route for 5HT from the synaptic gap, leading to the development of 5HT syndrome. Preclinical studies suggest that 5-HT syndrome is mainly caused by the activation of postsynaptic 5HT1 receptors. However, it is also thought to be related to 5HT2 receptors. Gramam et al. and Marley and Wozniak suggested that the balance between 5HT blocking and dopamine reuptake potency of antidepressants determines the risk of 5HT syndrome, and that antidepressants with significant effects on 5HT reuptake and minimal effects on dopamine (e.g., paroxetine, clomipramine) may have a higher risk when combined with MAOI The above conclusions are not yet confirmed by strong evidence. Clinical manifestations: The 5HT syndrome is generally considered to be clinically manifested in the following three areas; cognitive and behavioral disturbances: manifested as impaired consciousness, agitation, and behavioral disturbances. However, these conditions are easily overlooked in the early stages and are easily confused with the patient’s psychiatric symptoms, which are often clinically considered to be an aggravation and worsening of the patient’s psychiatric symptoms, which include anxiety, agitation, mild mania, headache, and sleep disturbance. Further development may lead to grand mal seizures and coma. Disturbances of the vegetative nerves: fever, chills, sweating, diarrhea, differential response to blood pressure, vomiting, and nausea are more common clinically, but occasionally dilated pupils and loss of pupillary response to light, skin flushing, and abdominal cramps are seen. Neuromuscular abnormalities: myoclonus, hyperreflexia, ataxia, tremor. They are the most common symptoms, but tremors at rest, teeth chatter, and difficulty walking are often falsely attributed to other causes. In most severe cases, generalized muscle tonus occurs, with sustained muscle contraction leading to increased body temperature, metabolic acidosis, rhabdomyolysis, and impaired respiratory function. Muscle tonus may also be relatively limited to the lower extremities, with hyperreflexia of the lower extremities and bilateral Babinski positivity. Diagnosis: Sternbach’s criteria for the diagnosis of 5HT syndrome: A. The presence of at least three of the following clinical features is required to increase the dose of a known 5HTergic drug in addition to the definitive dosing regimen: myoclonus, hyperreflexia, chills, sweating, diarrhea, fever, ataxia, and tremor. ataxia, and tremor. B. Other etiologic causes (e.g., infection, metabolism, substance abuse, withdrawal) have been ruled out C. No antipsychotic use prior to the onset of symptoms But Sternbach’s diagnostic criteria are broad, and many of them can occur with a single 5HT reuptake inhibitor. Lejoyeux et al. found in a group of 38 patients on clomipramine (75 mg/d over three days to 150 mg/d) that 26% of patients were considered to meet Sternbach’s diagnostic criteria. Therefore, caution should be exercised when using the above criteria, depending on the clinical symptoms of the patient. The differential diagnosis: malignant syndrome: is an idiosyncratic response of the patient to various psychotropic agents, most commonly antagonistic D2 psychotropic agents with high potency, also thought to occur after withdrawal of dopamine agonists, its onset is often associated with increasing doses of psychotropic agents, but nowadays it has also been reported to start after concomitant use of lithium, fluoxetine, and 5HTergic drugs such as MAOI. Malignant syndrome is rare when antidepressants are used alone. The development of malignant syndrome symptoms is slower compared to 5HT syndrome, often taking days to weeks, and the symptoms are generally slow to subside. Disorders of consciousness, sweating, disturbances of the vegetative nervous system, increased body temperature, extrapyramidal symptoms, and elevated creatinine kinase can be found in both syndromes. However, muscle tonicity and elevated creatinine kinase are often the main manifestations in the malignant syndrome, whereas tremor, myoclonus and diarrhea are more prominent in the 5HT syndrome. In addition, the increase in body temperature in 5HT syndrome is often less severe than in malignant syndrome, and the magnitude of creatinine kinase elevation is lower than in malignant syndrome. Treatment: 1. Discontinue the medication in question: 5HT syndrome is a self-limiting disease that often disappears quickly after 24 hours of drug withdrawal. Therefore discontinuation of the drug in question is a clinically necessary option. 2. Use of anti-5HTergic drugs: Generally used when symptoms persist or are severe. Methicillin: 2-6mg, the highest dose 6mg/d Cycloheximide: starting dose 4-8mg, after that 4mg every 2-4 hours, total 0.5mg/kg/d In addition some antipsychotic drugs have blocking effect on 5HT2 receptor: such as clozapine, chlorpromazine, and Vestone can also be considered under certain circumstances. However, because these drugs may lower the seizure threshold in patients with 5HT syndrome, clinical application should be noted. 3, supportive treatment: cooling: body temperature is not high is given physical cooling, if necessary, the use of drugs. The use of benzodiazepines: effective for muscle tonicity and seizures caused by 5HT. They can be given intramuscularly or intravenously. Usually depends on the condition. Prevention: Try to avoid using more than 2 5HTergic drugs at the same time, and observe closely if they must be used, especially in elderly patients. If the above symptoms occur, especially if the patient has problems with consciousness, the possibility of this disorder should be considered and the drug should be reduced or stopped immediately to avoid unnecessary consequences.