Affiliation:
1. Center for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
2. Office of the Dean, Icahn School of Medicine at Mount Sinai, New York, New York
3. Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
4. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
Abstract
Abstract
Background
Since about one-third of patients with major depressive disorder (MDD) do not respond adequately to available antidepressants, there is a need for treatments based on novel mechanisms of action. Neuropeptide Y (NPY), a normal brain constituent, is reduced in cerebrospinal fluid of patients with MDD and post-traumatic stress disorder and in corresponding rodent models. Moreover, NPY administered centrally or intranasally rescues pathophysiology in these models. Consequently, we conducted the first, to our knowledge, controlled trial of NPY as a treatment for MDD.
Methods
Thirty MDD patients on a stable dose of a conventional antidepressant insufflated 6.8 mg NPY (n = 12) or placebo (n = 18) in a double blind randomized fashion. Effects were assessed at baseline, +1 hour, +5 hours, +24 hours, and +48 hours. The primary outcome was change in depression severity measured with the Montgomery-Åsberg Depression Rating Scale (MADRS).
Results
NPY was superior to placebo at +24 hours (change −10.3 [95% CI: −13.8; −6.8]) vs −5.6 (95% CI: −8.4; −2.7); group*time F = 3.26, DF = (1,28), P = .04; Cohen’s d = 0.67). At +5 hours MADRS decreased −7.1 ([95% CI: −10.0; −4.2] vs −3.5 [95% CI: −5.8; −1.2]; group*time F = 2.69, DF = (1,28), P = .05; Cohen’s d = 0.61). MADRS reduction at +48 hours was not significant.
Conclusions
Since no results regarding the trajectory of NPY effects existed prior to this study we extrapolated from the known NPY biology and predicted the effects will occur 5–48 hours post insufflation. We chose +48 hours as the primary endpoint and +1, +5, and +24 hours as secondary endpoints. The results, the first of their kind, indicate that insufflated NPY is antidepressant, despite not meeting the primary outcome, and call for dose ranging and repeated NPY insufflation trials.
Clinical Trial Registration
EudraCT Number: 2014-000129-19.
Funder
Swedish Medical Research Council
Stockholm County Council-Karolinska Institutet
Center for Psychiatry Research
Department of Clinical Neuroscience
Karolinska Institutet
Torsten Söderbergs Stiftelse
Anne and Joel Ehrenkranz Laboratory
Study of Human Resilience
Icahn School of Medicine at Mount Sinai
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Psychiatry and Mental health,Pharmacology
Cited by
21 articles.
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