(1) Increasing salt and fluid intake therapy: Increasing salt intake and increasing fluid intake in the diet is the basis for the treatment of VVS. Younoszai et al. also found that oral fluid therapy in 28 children with VVS significantly reduced the number of seizures or alleviated the symptoms in the children. We also found that health education for children with VVS, including increased salt and water intake, resulted in relief of symptoms in 20% of children. Because salt supplementation and increased fluid intake are relatively safe and easily accepted by children and their parents, they are highly recommended as initial treatment for children with VVS. (2) β-blockers: These drugs are the most commonly used in the treatment of children with VVS. They work by reducing the stimulation of cardiac pressure receptors or by blocking the effects of high levels of circulating catecholamines. Several studies have previously found that β-blockers (mainly atenolol or metoprolol) are effective in the treatment of children with VVS, and their efficacy has been investigated by our group [17]. Recently, however, a randomized double-blind placebo-controlled study in adults with VVS found that beta-blockers may be ineffective in treating patients with VVS. Sheldon et al. explored the Prevention of Syncope Attacks Trial (POST) study of metoprolol in adults with VVS. The study population consisted of 208 VVS (mean age 42±18 years). A double-blind and randomized placebo-controlled design was used. Treatment group (n=108) and control group (n=100). The results showed that there was no significant difference between the two groups in preventing recurrence of syncope. This inconsistency in the results of the study was also explored, and it was found that the application of beta-blockers may be more effective for those who have a significant increase in heart rate (heart rate >30 beats/min compared to the basal value) before a positive response during HUT. (3) α-agonists: This drug exerts its therapeutic effect by increasing peripheral vasoconstriction and reducing venous blood volume. Strieper et al. studied the therapeutic effect of phenylephrine in children with VVS. They administered phenylephrine (60 mg/d, 2 times/d) to 16 children with VVS, and the HUT was reviewed after a mean follow-up of 11.7 months. 15 children were asymptomatic and reappeared. In addition, midodrine is a selective a1 agonist and has been shown to be effective in the treatment of refractory VVS in several studies to date. Our group also investigated the effect of midodrine in children with VVS. Twenty-six children (mean age 12.2±2.9 years) with VVS (recurrent syncope, HUT positive) were divided into a midodrine group and a basic treatment group (including education, recommendation to increase salt and water intake) and followed up for 6 months. The results showed that the HUT conversion rate was 75% and 20% in the two groups, respectively, and the HUT conversion rate was significantly higher in the midodrine group than in the basic treatment group (p<0.05). The recurrence rates of syncope were 22.22% and 80.00% during the follow-up, and the recurrence rates of syncope were significantly lower in both groups (p<0.05). This suggests that midodrine (2.5 mg, 2 times/d) is effective in treating children with VVS. The results of our recent Meta-analysis of a-agonists in the treatment of VVS also support the effectiveness of this drug in treating VVS patients. (4) Fludrocortisone: This drug is effective in treating VVS patients by increasing renal reabsorption of sodium to expand blood volume, and also by affecting pressure receptor sensitivity, increasing vasoconstrictor response and decreasing parasympathetic activity. Some studies have found significant improvement in symptoms and reduction in recurrence of syncope in children with VVS. However, Salim et al. used a randomized, double-blind, placebo-controlled study to investigate fludrocortisone and increased salt intake to prevent recurrence of syncope in children with VVS, and found that fludrocortisone did not reduce recurrence of syncope in children taking fludrocortisone. (5) 5-HT preuptake inhibitors: These drugs prevent syncope by inhibiting synaptic gap 5-HT reuptake, increasing synaptic gap 5-HT concentration, compensatory downregulation of postsynaptic membrane 5-HT receptors, and diminishing the response to rapid central 5-HT changes, thereby attenuating the rapid sympathetic inhibitory response. The reports of application in pediatric VVS patients are empirical application reports, and no randomized controlled studies have been performed. For example, Grubb et al. treated 17 children with unexplained syncope and positive HUT with the 5-HT preuptake inhibitor sertraline (50 mg/d), and 9 of them had disappearance of symptoms and negative repeat HUT at 12±5 months of follow-up. After 7±3 months of follow-up, 1/2 of the children were syncope free and had a negative repeat HUT, and 3 of them discontinued the drug because they could not tolerate it. The effectiveness of this drug in the treatment of children with VVS needs to be further confirmed in more scientific randomized controlled studies. Moreover, these drugs are antipsychotics, which are not easily accepted by children and their parents.