Using Clonidine for neuromodulation in patients with postural orthostatic tachycardia syndrome

Microneurography studies showed that the alpha-2 agonist clonidine suppresses sympathetic nerve activity. However, clonidine's neuromodulation effects in ambulatory patients are unknown. To test the hypothesis that clonidine suppresses skin sympathetic nerve activity (SKNA) and decreases heart rate (HR) in patients with hyperadrenergic postural orthostatic tachycardia syndrome (POTS). This prospective observational study included 33 patients with POTS treated with clonidine. We recorded ambulatory neuECG for 24 hours before clonidine and 3 days afterward. A follow-up recording was done 6 months later. Symptomatic episodes were documented by diary and button press. Overall, 26 participants (24 women) completed the first recording. Ten participants (38%) completed the follow-up recordings and experienced fewer symptomatic episodes (P = .030) and lower 24-hour average HR (P = .020) at follow-up than at baseline. The ratio of low frequency and high frequency SKNA significantly decreased on days 1-3 (P = .001, P <.001, and P <.001, respectively). SKNA burst frequency was significantly reduced on days 1 (P = .010) and 2 (P = .012). The 24-hour average HR decreased significantly on days 1-3 (P = .005, P <.001, and P <.001, respectively). The maximum HR during the day also significantly decreased on day 2 (P = .043) and day 3 (P <.001). Eleven had sympathetic toggled sinus rate acceleration episodes. Sinus rate acceleration burden and duration decreased in 7 of 11 patients (64%). In 3 participants, clonidine induced episodic bradycardia and sinus arrhythmia. In hyperadrenergic POTS, clonidine reduced SKNA and the low frequency/high frequency ratio. Ten participants (38%) used clonidine for > 6 months, and most (8/10, or 80%) had fewer symptoms than at baseline.