. 2018 Mar 22;20(4):794–797. doi: 10.1111/jch.13260

Table 1.

Review of the literature on atomoxetine in OH

Study purpose	Methods	Main results	Study implications
To compare atomoxetine and midodrine in improving upright SBP in patients with neurogenic orthostatic hypotension	Randomized, single‐blind, crossover study9	Atomoxetine improves upright blood pressure to a greater extent than midodrine (mean difference, 7.5 mm Hg; 95% CI, 0.6–14.5 [P = .03]) Only atomoxetine improved orthostatic hypotension–related symptoms (for atomoxetine vs placebo, improvement in quartile 1 (0.6 SQRT points; 95% CI, −0.1 to 1.7 [P = .03]), while for midodrine vs placebo, no improvement in quartile 1 (0.6 SQRT point; 95% CI, −1.6 to 0.5 [P = .29])	Additional studies are required to address the long‐term efficacy of atomoxetine Atomoxetine, when given at pediatric doses, may be an alternative therapy for patients who do not experience symptom relief with midodrine
To assess atomoxetine use for 10 wk in an elderly patient with primary orthostatic hypotension	Case report10	Variability in SBP readings significantly improved along with symptoms	For patients in whom other hypotensive therapies have failed, atomoxetine may be considered as an alternative Clinicians should be aware that a low dosage of atomoxetine is effective and safe for symptom improvement and blood pressure control in orthostatic hypotension Large prospective randomized trials are needed to explore the efficacy and safety of atomoxetine use in primary orthostatic hypotension, especially in younger patients
To test the pressor effect of 18 mg of atomoxetine in 21 patients with damage of the central (10 patients) and peripheral (11 patients) autonomic nervous system	Randomized, crossover, placebo‐controlled design12	Atomoxetine significantly increased seated and standing SBP in patients with central autonomic failure as compared with placebo (slope difference 0.92; 95% CI, 0.73–1.11 [P ≤ .001]) At the end of the observation period, the mean seated SBP in the atomoxetine group was in the hypertensive range (149 ± 26, range 113–209 mm Hg) In patients with peripheral autonomic failure, atomoxetine did not elicit a pressor response (slope difference 0.16; 95% CI, −0.02 to 0.34 [P = .08])	These findings suggest that a functional central sympatholytic pathway is essential to avoid hypertension in patients treated with this drug Caution should be exercised when this medication is used in patients with milder forms of autonomic impairment

Study purpose

Methods

Main results

Study implications

To compare atomoxetine and midodrine in improving upright SBP in patients with neurogenic orthostatic hypotension

Randomized, single‐blind, crossover study9

Atomoxetine improves upright blood pressure to a greater extent than midodrine (mean difference, 7.5 mm Hg; 95% CI, 0.6–14.5 [P = .03])

Only atomoxetine improved orthostatic hypotension–related symptoms (for atomoxetine vs placebo, improvement in quartile 1 (0.6 SQRT points; 95% CI, −0.1 to 1.7 [P = .03]), while for midodrine vs placebo, no improvement in quartile 1 (0.6 SQRT point; 95% CI, −1.6 to 0.5 [P = .29])

Additional studies are required to address the long‐term efficacy of atomoxetine

Atomoxetine, when given at pediatric doses, may be an alternative therapy for patients who do not experience symptom relief with midodrine

To assess atomoxetine use for 10 wk in an elderly patient with primary orthostatic hypotension

Case report10

Variability in SBP readings significantly improved along with symptoms

For patients in whom other hypotensive therapies have failed, atomoxetine may be considered as an alternative

Clinicians should be aware that a low dosage of atomoxetine is effective and safe for symptom improvement and blood pressure control in orthostatic hypotension

Large prospective randomized trials are needed to explore the efficacy and safety of atomoxetine use in primary orthostatic hypotension, especially in younger patients

To test the pressor effect of 18 mg of atomoxetine in 21 patients with damage of the central (10 patients) and peripheral (11 patients) autonomic nervous system

Randomized, crossover, placebo‐controlled design12

Atomoxetine significantly increased seated and standing SBP in patients with central autonomic failure as compared with placebo (slope difference 0.92; 95% CI, 0.73–1.11 [P ≤ .001])

At the end of the observation period, the mean seated SBP in the atomoxetine group was in the hypertensive range (149 ± 26, range 113–209 mm Hg)

In patients with peripheral autonomic failure, atomoxetine did not elicit a pressor response (slope difference 0.16; 95% CI, −0.02 to 0.34 [P = .08])

These findings suggest that a functional central sympatholytic pathway is essential to avoid hypertension in patients treated with this drug

Caution should be exercised when this medication is used in patients with milder forms of autonomic impairment

CI, confidence interval; OH, orthostatic hypotension; SBP, systolic blood pressure; SQRT, square‐rooted transformed.