Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension.

OBJECTIVE To evaluate the long-term (for up to 3 months) efficacy and safety of single or combined therapy with midodrine and pyridostigmine for neurogenic orthostatic hypotension (OH). METHODS This was a randomized, open-label clinical trial. In total, 87 patients with symptomatic neurogenic OH were enrolled and randomized to receive 1 of 3 treatments: midodrine only, pyridostigmine only, or midodrine + pyridostigmine. The patients were followed up at 1 and 3 months after treatment. The primary outcome measures were improvement in orthostatic blood pressure (BP) drop at 3 months. Secondary endpoints were improvement of the orthostatic BP drop at 1 month and amelioration of the questionnaire score evaluating OH-associated symptoms. RESULTS Orthostatic systolic and diastolic BP drops improved significantly at 3 months after treatment in all treatment groups. Orthostatic symptoms were significantly ameliorated during the 3-month treatment, and the symptom severity was as follows: midodrine only < midodrine + pyridostigmine < pyridostigmine only group. Mild to moderate adverse events were reported by 11.5% of the patients. CONCLUSIONS Single or combination treatment with midodrine and pyridostigmine was effective and safe in patients with OH for up to 3 months. Midodrine was better than pyridostigmine at improving OH-related symptoms. CLINICALTRIALSGOV IDENTIFIER NCT02308124. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that for patients with neurogenic OH, long-term treatment with midodrine alone, pyridostigmine alone, or both midodrine and pyridostigmine is safe and has similar effects in improving orthostatic BP drop up to 3 months.