Efficacy of Propranolol, Bisoprolol, and Pyridostigmine for Postural Tachycardia Syndrome: a Randomized Clinical Trial

Abstract

Postural tachycardia syndrome (POTS) is a form of dysautonomia which presents with complex symptoms including orthostatic intolerance. Several medications are prescribed for POTS; however, the efficacy of sustained medical treatment has not been well-investigated. Here, we conducted a 2 × 2 factorial design, randomized, clinical trial of a 3-month medical treatment regimen in POTS patients. Patients were randomly allocated to 4 treatment groups (Group 1: propranolol; Group 2: bisoprolol; Group 3: propranolol + pyridostigmine; Group 4: bisoprolol + pyridostigmine). The orthostatic intolerance questionnaire (OIQ), Beck depression inventory-II (BDI-II), and short-form health survey (SF-36) were conducted at baseline, 1 and 3 months after treatment. Seventy-seven patients who completed the 3-month follow-up were analyzed. In total, every clinical score improved significantly after medical treatment. The OIQ score was significantly lower than that at baseline (18.5 ± 6.7) after 1 month (12.5 ± 4.5, P < 0.01), which decreased further after 3 months (7.8 ± 5.7, P < 0.01). The OIQ score improvements were consistent across every treatment group. In the subgroup analysis of 59 patients who did not receive antidepressants, the BDI-II score significantly decreased after treatment, regardless of the regimen. Physical components of the SF-36 improved after 3 months in every group, while mental components improved only in Group 3. The amount of changes in each score was similar among groups throughout the comparisons. Sustained medical treatment is beneficial to POTS patients, not only for orthostatic intolerance symptoms but also for depression and diminished quality of life, even without prescriptions for antidepressants. The efficacy of each regimen in POTS patients was comparable.

Trial registration: NCT02171988.

Keywords: Bisoprolol; Postural tachycardia syndrome; Propranolol; Pyridostigmine; Randomized trial.

Fig. 1

Screening, randomization, treatment, and follow-up of the patients. Among the 154 patients with excessive orthostatic tachycardia, 50 patients with mild orthostatic intolerance symptoms were excluded. The remaining 103 patients were randomly assigned to 4 treatment groups. Patients who completed the 3-month medical treatment regimen were included in the analysis

Fig. 2

Subgroup analysis of the patients who did not receive antidepressants during the follow-up period. Regardless of the treatment group, all the patients demonstrated noticeable improvement of their orthostatic intolerance symptoms (measured by the OIQ) and depression (measured by the BDI-II) after 1 month, with further improvement after 3 months of medical treatment. Patients in every treatment group experienced improvement of the physical component of quality of life (measured by PCS) after 3 months, except ambiguous improvement in Group 2. Patients in Group 3 (who received propranolol and pyridostigmine) showed an improvement of the mental component of quality of life (measured by the MCS) after 3 months. P and B indicate propranolol and bisoprolol, respectively; PS, pyridostigmine; OIQ, orthostatic intolerance questionnaire; BDI-II, Beck Depression Inventory-II; PCS, physical component summary scale of the Short-Form 36; MCS, mental component summary scale of the Short-Form 36. *P values < 0.01 on repeated measures ANOVA performed among baseline, 1 month, and 3 months. **P values < 0.05 on repeated measures ANOVA performed among baseline, 1 month, and 3 month. ^†P values < 0.01 on pairwise comparison with Bonferroni correction compared to the baseline. ^‡P values < 0.05 on pairwise comparison with Bonferroni correction compared to the baseline. ^¶P values < 0.01 on pairwise comparison with Bonferroni correction between 1 and 3 months. ^#P values < 0.05 on pairwise comparison with Bonferroni correction between 1 and 3 months

Fig. 3

Subgroup analysis of the patients combined according to the type of β-blockers or the presence of pyridostigmine. Among the patients who did not receive antidepressants throughout the follow-up period, patients were combined according to the choice of β-blocker or the presence of pyridostigmine. The delta changes of each clinical scale after 1- and 3-month medical treatment regimens are displayed (mean ± SD). The propranolol group designates the combined cohort (Groups 1 and 3) of patients who received propranolol, and the bisoprolol group designates the merged cohort (Groups 2 and 4) of patients who received bisoprolol as the choice of β-blocker (A). There was no significant difference in efficacy between the two β-blockers. Pyridostigmine (+) group refers to the combined cohort (Groups 3 and 4) of patients who received pyridostigmine with a β-blocker, while the pyridostigmine (−) group refers to the combined cohort (Groups 1 and 2) of patients who were treated with β-blockers only (B). There was no significant difference in efficacy according to the presence of pyridostigmine (all P > 0.05)