Paroxetine Vasovagal Syncope
abstract & commentary
Source: Calkins H. Pharmacologic approaches to therapy for vasovagal syncope. Am J Cardiol 1999;84:20Q-25Q.
Vasovagal syncope (vvs) is a relatively common disorder involving autonomic cardiovascular dysregulation. VVS typically is not a dangerous disorder, but it can be somewhat disabling in severe cases. Although nonpharmacologic modalities such as salt and fluid loading may be used to treat VVS, many pharmacologic agents have been proposed as effective in the management of this condition. Most of the available data are based on nonrandomized clinical trials. In fact, only atenolol, midodrine, and paroxetine have demonstrated efficacy in the treatment of vasovagal syncope in at least one randomized, placebo-controlled clinical trial. Other therapies commonly used in treating syncope include increased salt and fluid intake and fludrocortisone. In the current review, Calkins provides a summary of currently available data that support or question the use of various pharmacologic agents for treatment of vasovagal syncope.
VVS is thought to be the result of a paradoxic reflex that occurs when reduced venous pooling results in an increase in catecholamines. This increase is followed by mechanoreceptor stimulation throughout the heart and the pulmonary artery. This stimulation results in an abrupt increase in vagal tone. As a result of increased vagal tone, bradycardia and vasodilation occur, which, along with the existing condition of venous pooling, lead to dizziness and syncope. Pharmacotherapy may be targeted at either the efferent limb of the reflex (increased vagal tone or vasodilation) or the afferent limb (increased venous pooling).
Beta blockers are used to treat VVS because they block the increase in catecholamines that result from the increased venous pooling. Despite the fact that there are several reports on the efficacy of beta blockers in the literature, there is only one randomized, placebo-controlled trial (RCT) that supports their use. The study (n = 42) reported that atenolol improved orthostatic hypotension in 62% compared to only 5% of those taking placebo (P = 0.0004). Although other studies were not RCTs, similar results have been exhibited for the other beta blockers. Alpha-1 receptor agonists also may be used to treat VVS by inducing vasoconstriction. The only RCT using midodrine showed efficacy in 16 patients who experienced 7.3 more symptom-free days than those receiving placebo (P < 0.0001). Selective serotonin reuptake inhibitors (SSRIs) may help relieve VVS by down-regulating certain post-synaptic serotonin receptors that are believed to be involved in mediating vasodilation. Paroxetine is the only SSRI that has shown efficacy in an RCT. After one month of therapy with 20 mg/d, 62% of paroxetine-treated patients became symptom-free upon tilt-table testing vs. 38% of placebo-treated patients (P < 0.0001). Surprisingly, one of the agents quite commonly used, fludrocortisone, has not been evaluated by an RCT.
Comment by Michael F. Barber, pharmD
The current review supports the use of paroxetine for use in patients with VVS. Ideal candidates would be those who may not be able to tolerate beta blockers (such as asthmatics) or those patients with depression or other disorders for which SSRIs are indicated (obsessive-compulsive disorder, panic disorder, etc.). Notably, there seemed to be a lag in time to onset of therapeutic benefit for SSRI-treated patients compared to other agents (although head-to-head studies have not been performed). This is consistent with the time to onset of relief from depressive symptoms and may be related to the amount of time needed to down-regulate post-synaptic serotonin receptors. In published studies of SSRIs for use in VVS, there were several patients who dropped out due to intolerable adverse effects, suggesting that some patients may need to be titrated more slowly.
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