Trial reportHypertension (Dallas, Tex. : 1979)2019
Synergistic Pressor Effect of Atomoxetine and Pyridostigmine in Patients With Neurogenic Orthostatic Hypotension.
Trial report in Hypertension (Dallas, Tex. : 1979), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pyridostigmine in the management of orthostatic hypotension: a systematic review and meta-analysis.Open heart · 2025Pooled it
- Clinical Correlates of Efficacy of Pyridostigmine in the Treatment of Orthostatic Hypotension.Hypertension (Dallas, Tex. : 1979) · 2025Trial
- Atomoxetine on neurogenic orthostatic hypotension: a randomized, double-blind, placebo-controlled crossover trial.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2024Trial
- Efficacy of atomoxetine versus midodrine for neurogenic orthostatic hypotension.Annals of clinical and translational neurology · 2020Trial
- Cardiovascular autonomic failure correlates with cutaneous autonomic denervation in PD and MSA.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Approach to Cardiovascular Autonomic Dysfunction in Patients with Synucleinopathies.Movement disorders clinical practice · 2025Review
- Review
- Review
- Neurogenic Orthostatic Hypotension in Parkinson Disease-A Narrative Review of Diagnosis and Management.Journal of clinical medicine · 2025Review
- Update on the Treatment of Autonomic Disorders.Current treatment options in neurology · 2025Article
- Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Review
- Non-pharmacological and drug treatment of autonomic dysfunction in multiple system atrophy: current status and future directions.Journal of neurology · 2023Review
- Effects of Atomoxetine for the Treatment of Neurogenic Orthostatic Hypotension in Patients With Alpha-synucleinopathies: A Systematic Review of Randomized Controlled Trials and a Focus-Group Discussion.Journal of clinical neurology (Seoul, Korea) · 2023Article
- New horizons in the ageing autonomic nervous system: orthostatic hypotension and supine hypertension.Age and ageing · 2022Article
- Orthostatic Hypotension: Management of a Complex, But Common, Medical Problem.Circulation. Arrhythmia and electrophysiology · 2022Review
- Management of Orthostatic Hypotension in the Hospitalized Patient: A Narrative Review.The American journal of medicine · 2022Review
- The Pathogenesis and Treatment of Cardiovascular Autonomic Dysfunction in Parkinson's Disease: What We Know and Where to Go.Aging and disease · 2021Review
- Pharmacologic treatment of orthostatic hypotension.Autonomic neuroscience : basic & clinical · 2020Review
- Current Symptomatic and Disease-Modifying Treatments in Multiple System Atrophy.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Patients with autonomic failure are characterized by disabling orthostatic hypotension because of impaired sympathetic activity, but even severely affected patients have residual sympathetic tone which can be harnessed for their treatment. For example, norepinephrine transporter blockade with atomoxetine raises blood pressure (BP) in autonomic failure patients by increasing synaptic norepinephrine concentrations; acetylcholinesterase inhibition with pyridostigmine increases BP by facilitating ganglionic cholinergic neurotransmission to increase sympathetic outflow. We tested the hypothesis that pyridostigmine will potentiate the pressor effect of atomoxetine and improve orthostatic tolerance and symptoms in patients with severe autonomic failure. Twelve patients received a single oral dose of either placebo, pyridostigmine 60 mg, atomoxetine 18 mg or the combination on separate days in a single blind, crossover study. BP was assessed seated and standing before and 1-hour postdrug. In these severely affected patients, neither pyridostigmine nor atomoxetine improved BP or orthostatic tolerance compared with placebo. The combination, however, significantly increased seated BP in a synergistic manner (133±9/80±4 versus 107±6/66±4 mm Hg for placebo, 105±5/67±3 mm Hg for atomoxetine, and 99±6/64±4 mm Hg for pyridostigmine; P<0.001); the maximal increase in seated BP with the combination was 33±8/18±3 mm Hg at 60 minutes postdrug. Only the combination showed a significant improvement of orthostatic tolerance and symptoms. In conclusion, the combination pyridostigmine and atomoxetine had a synergistic effect on seated BP which was associated with improvement in orthostatic tolerance and symptoms. This pharmacological approach could be useful in patients with severe autonomic failure but further safety and long-term efficacy studies are needed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.