A randomized dose-ranging study of neuropeptide Y in patients with posttraumatic stress disorder
Open accessAbstract
Background: Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Methods: Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Results: Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Conclusions: Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519).
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In a randomised clinical Phase 1 trial in patients with PTSD, intranasally administered NPY showed a greater reduction in anxiety symptoms in a dose-dependent manner along with good tolerability than placebo.
“In a recent randomised clinical Phase 1 trial in patients with PTSD, intranasally administrated NPY showed a greater reduction in anxiety symptoms in a dose-dependent manner along with good tolerability than placebo, supporting the push for further studies investigating the efficacy and safety of the repeated administration of NPY”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Sayed et al., 2018
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- Authors
- Sayed, S., Van Dam, N. T., Horn, S. R., Kautz, M. M., Parides, M., Costi, S., Collins, K. A., Iacoviello, B., Iosifescu, D. V., Mathé, A. A., Southwick, S. M., Feder, A., Charney, D. S., & Murrough, J. W.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Click Therapeutics, Inc. (United States) (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Karolinska Institutet (SE)
- Yale University (US)
- Corresponding author
- Murrough, James W
- ORCID
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-11-23
- Volume
- 21
- Issue
- 1
- Pages
- 3-11
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC5795352
- OpenAlex
- W2769519341
- Cited by
- 79
- References
- 54
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 13 · 2019: 9 · 2018: 6
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Funders
- Icahn School of Medicine at Mount Sinai
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- neuropeptide Y, post-traumatic stress disorder, intranasal administration, anxiolytic efficacy, tolerability, dose-response relationship, anxiety, stress-related disorders
- MeSH terms
- Adult, Anxiety, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Neuropeptide Y, Psychiatric Status Rating Scales, Stress Disorders, Post-Traumatic, Cohort Studies, Treatment Outcome, Outcome Assessment, Health Care, Cross-Over Studies, Neuroprotective Agents
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