Levomilnacipran in Healthy Males

Summary

Levomilnacipran is an antidepressant currently approved in Canada to treat Major Depressive Disorder (MDD). Thirty-six healthy male participants will receive escalating doses of levomilnacipran, duloxetine, or placebo every 7 days (+/- 1 day) throughout a 20 - 28 day period. After each dose escalation study participants will be asked to come to the clinic to conduct the necessary tests - these will include tyramine pressor tests as well as blood draws. The results of this study will allow the investigators to determine the dose(s) of levomilnacipran at which reuptake inhibition of norepinephrine and serotonin (chemicals utilized by nerve cells to transmit information to other cells) is achieved.

Timeline

Start

2018-03-02

Primary completion

2019-12-31

Completion

2022-05-01

Publications

• Background Asnis GM, Henderson MA. Levomilnacipran for the treatment of major depressive disorder: a review. Neuropsychiatr Dis Treat. 2015 Jan 9;11:125-35. doi: 10.2147/NDT.S54710. eCollection 2015.
• Background Auclair AL, Martel JC, Assie MB, Bardin L, Heusler P, Cussac D, Marien M, Newman-Tancredi A, O'Connor JA, Depoortere R. Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety. Neuropharmacology. 2013 Jul;70:338-47. doi: 10.1016/j.neuropharm.2013.02.024. Epub 2013 Mar 13.
• Background Blier P, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Debonnel G. Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers. Int J Neuropsychopharmacol. 2007 Feb;10(1):41-50. doi: 10.1017/S1461145705006395. Epub 2006 May 11.
• Background Aldosary F, Norris S, Tremblay P, James JS, Ritchie JC, Blier P. Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder. Int J Neuropsychopharmacol. 2022 Apr 19;25(4):283-292. doi: 10.1093/ijnp/pyab086.
• Background Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol. 2007 Feb;10(1):51-61. doi: 10.1017/S1461145705006413. Epub 2006 May 11.
• Background First, M.B., Williams, J.B.W., Karg, R.S., & Spitzer, R.L. (2015). Structured clinical interview for DSM-5-research version. Arlington: American Psychiatric Association.
• Background Gobbi G, Slater S, Boucher N, Debonnel G, Blier P. Neurochemical and psychotropic effects of bupropion in healthy male subjects. J Clin Psychopharmacol. 2003 Jun;23(3):233-9. doi: 10.1097/01.jcp.0000084023.22282.03.
• Background Turcotte JE, Debonnel G, de Montigny C, Hebert C, Blier P. Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology. 2001 May;24(5):511-21. doi: 10.1016/S0893-133X(00)00220-7.
• Background Vincent S, Bieck PR, Garland EM, Loghin C, Bymaster FP, Black BK, Gonzales C, Potter WZ, Robertson D. Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004 Jun 29;109(25):3202-7. doi: 10.1161/01.CIR.0000130847.18666.39. Epub 2004 Jun 7.
• Nikolitch K, Phillips JL, Daniels S, Blier P. Levomilnacipran, but Not Duloxetine, Inhibits Serotonin and Norepinephrine Reuptake Throughout Its Therapeutic Range. J Clin Psychiatry. 2025 Aug 25;86(3):25m15867. doi: 10.4088/JCP.25m15867.

Drugs

Indications

No indication recorded.