Efficacy and Safety of Midodrine and Atomoxetine for Neurogenic OH

Efficacy and Safety of Midodrine and Atomoxetine Treatment in Patients With Neurogenic Orthostatic Hypotension : A Prospective Randomized Study

This was a randomized, open-label clinical trial. We will enroll patients with symptomatic neurogenic OH and randomize them to 1 of 2 treatments: (1) midodrine only, (2) atomoxetine only. We will follow up patients at 1 and 3 months after treatment. If the patients meet BP criteria for OH at 1 month, they will receive combination treatment with both midodrine and atomoxetin. The primary outcome measure is amelioration of questionnaire score evaluating OH-associated symptoms at 3 months. Secondary end-points were improvement in orthostatic blood pressure (BP) drop at 1 and 3 months.

Visit 1.

1. Enroll, baseline evaluation of the patients

2. Questionnaire

   • Evaluate orthostatic hypotension symptom: Orthostatic Hypotension Questionnaire (OHQ)
   • Quality of life: Korean version of Short-form 36
   • Depressive symptom: Korean version of Beck Depression Inventory(BDI)-2

3. Blood test (6cc): ELISA for alpha 1,2 and beta 1,2 adrenergic receptor antibody and nicotinic acetylcholine receptor antibody. Preserve sample for genetic testing.

4. Randomization: randomize patients to three group in 1:1 ratio (Midodrine 5mg/day single, Atomoxetine 18mg/day single)

5. Treatment education Visit 2. 1 month after treatment Orthostatic BP check/ check drug compliance and side effect/ Questionnaire If the patients meet BP criteria for OH, initiate combination treatment (Midodrine 5mg/day+Atomoxetine 18mg/day) Visit 3. 3 months after treatment Orthostatic BP check/ check drug compliance and side effect/ Questionnaire

Inclusion Criteria:

• Age >=19 patients who complained of dizziness
• Orthostatic hypotension after 3-minute standing (systolic blood pressure drop >=20 or diastolic blood pressure drop >=10

Exclusion Criteria:

• Drug-induced hypotension, if necessary, evaluate patient after discontinuing the causative drug for one month
• Heart failure or Chronic renal failure
• Severe supine hypertension (Systolic Blood Pressure >180 or Diastolic Blood Pressure>110mmHg)
• Pregnant women, breast-feeding
• Unable to perform questionnaire