Treatment-Resistant Depression (TRD): Is the Opioid System Involved?

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Analgesics, Opioid*/pharmacology ; Analgesics, Opioid*/therapeutic use ; Trazodone*; Animals ; Mice ; Mianserin/pharmacology ; Mianserin/therapeutic use ; Venlafaxine Hydrochloride/pharmacology ; Venlafaxine Hydrochloride/therapeutic use ; Fluvoxamine ; Mirtazapine/pharmacology ; Mirtazapine/therapeutic use ; Fluoxetine ; Reboxetine ; Moclobemide ; Depression ; Antidepressive Agents/pharmacology ; Antidepressive Agents/therapeutic use ; Naloxone/pharmacology ; Naloxone/therapeutic use ; Dose-Response Relationship, Drug

About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed.

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601133461 Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases; 347300-00 Ari and Regine Aprijaskis Fund; 0601133671 Sylvan Adams Sports Institute

Keywords: antinociception; fluoxetine; fluvoxamine; mianserin; mice; mirtazapine; moclobemide; opioids; reboxetine; trazodone; treatment-resistant depression; venlafaxine

0 (Analgesics, Opioid)
250PJI13LM (Mianserin)
7D7RX5A8MO (Venlafaxine Hydrochloride)
O4L1XPO44W (Fluvoxamine)
A051Q2099Q (Mirtazapine)
01K63SUP8D (Fluoxetine)
947S0YZ36I (Reboxetine)
YBK48BXK30 (Trazodone)
PJ0Y7AZB63 (Moclobemide)
0 (Antidepressive Agents)
36B82AMQ7N (Naloxone)

Date Created: 20230714 Date Completed: 20230717 Latest Revision: 20230718

20240514

PMC10342252

10.3390/ijms241311142

37446323