Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation

Summary

This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram with an opioid on ventilation. Ventilation will be assessed using a rebreathing methodology. This study will evaluate chronic and acute dosing of paroxetine and escitalopram combined with an opioid as well as chronic and acute dosing of the two drugs without coadministration of an opioid. This study is a 3-period, randomized, placebo-controlled crossover study conducted with 25 healthy participants. Each participant will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, escitalopram/oxycodone) in a randomized order.

Timeline

Start

2022-09-01

Primary completion

2023-09-17

Completion

2023-09-17

Publications

• Background Xu L, Krishna A, Stewart S, Shea K, Racz R, Weaver JL, Volpe DA, Pilli NR, Narayanasamy S, Florian J, Patel V, Matta MK, Stone MB, Zhu H, Davis MC, Strauss DG, Rouse R. Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat. Clin Transl Sci. 2021 Nov;14(6):2208-2219. doi: 10.1111/cts.13080. Epub 2021 Jun 16.
• Background Rebuck AS. Measurement of ventilatory response to CO2 by rebreathing. Chest. 1976 Jul;70(1 Suppl):118-21. doi: 10.1378/chest.70.1_supplement.118. No abstract available.
• Background van der Schrier R, Jonkman K, van Velzen M, Olofsen E, Drewes AM, Dahan A, Niesters M. An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers. Br J Anaesth. 2017 Dec 1;119(6):1169-1177. doi: 10.1093/bja/aex295.
• Background van der Schrier R, Roozekrans M, Olofsen E, Aarts L, van Velzen M, de Jong M, Dahan A, Niesters M. Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals. Anesthesiology. 2017 Mar;126(3):534-542. doi: 10.1097/ALN.0000000000001505.
• Background Nutt DJ, Forshall S, Bell C, Rich A, Sandford J, Nash J, Argyropoulos S. Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders. Eur Neuropsychopharmacol. 1999 Jul;9 Suppl 3:S81-6. doi: 10.1016/s0924-977x(99)00030-9.
• Background Czachura JF, Rasmussen K. Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):266-75. doi: 10.1007/s002100000290.
• Background Casey K, Duffin J, McAvoy GV. The effect of exercise on the central-chemoreceptor threshold in man. J Physiol. 1987 Feb;383:9-18. doi: 10.1113/jphysiol.1987.sp016392.
• Background Duffin J, McAvoy GV. The peripheral-chemoreceptor threshold to carbon dioxide in man. J Physiol. 1988 Dec;406:15-26. doi: 10.1113/jphysiol.1988.sp017365.
• Background Dong TW, MacLeod DB, Santoro A, Augustine Z, Barth S, Cooter M, Moon RE. A methodology to explore ventilatory chemosensitivity and opioid-induced respiratory depression risk. J Appl Physiol (1985). 2020 Sep 1;129(3):500-507. doi: 10.1152/japplphysiol.00460.2020. Epub 2020 Jul 16.
• Background Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20-32. doi: 10.1111/imj.1967.16.1.20. No abstract available.
• Background Gorman JM, Browne ST, Papp LA, Martinez J, Welkowitz L, Coplan JD, Goetz RR, Kent J, Klein DF. Effect of antipanic treatment on response to carbon dioxide. Biol Psychiatry. 1997 Dec 1;42(11):982-91. doi: 10.1016/s0006-3223(97)00160-1.
• Background Bertani A, Perna G, Arancio C, Caldirola D, Bellodi L. Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study. J Clin Psychopharmacol. 1997 Apr;17(2):97-101. doi: 10.1097/00004714-199704000-00006.
• Background Robillard R, Saad M, Ray LB, BuJaki B, Douglass A, Lee EK, Soucy L, Spitale N, De Koninck J, Kendzerska T. Selective serotonin reuptake inhibitor use is associated with worse sleep-related breathing disturbances in individuals with depressive disorders and sleep complaints: a retrospective study. J Clin Sleep Med. 2021 Mar 1;17(3):505-513. doi: 10.5664/jcsm.8942.
• Florian J, Keshishi D, Gershuny V, Salcedo P, van der Schrier R, Burkhart K, Shah A, Racz R, Patel V, DePalma R, Matta M, Vegesna G, Hsiao CH, Rouse R, Fein M, Stone M, Dahan A, Strauss DG. Effect of Paroxetine or Escitalopram Coadministered with Oxycodone versus Oxycodone Alone on Ventilation during Hypercapnia: A Randomized Clinical Trial. Anesthesiology. 2026 Jul 1;145(1):98-110. doi: 10.1097/ALN.0000000000006043. Epub 2026 Mar 18.

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Indications