{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:11:09Z","timestamp":1783980669432,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ari and Regine Aprijaskis Fund","award":["347300-00"],"award-info":[{"award-number":["347300-00"]}]},{"name":"Ari and Regine Aprijaskis Fund","award":["601133461"],"award-info":[{"award-number":["601133461"]}]},{"name":"Ari and Regine Aprijaskis Fund","award":["0601133671"],"award-info":[{"award-number":["0601133671"]}]},{"name":"Dr. Miriam and Sheldon G. Adelson Center","award":["347300-00"],"award-info":[{"award-number":["347300-00"]}]},{"name":"Dr. Miriam and Sheldon G. Adelson Center","award":["601133461"],"award-info":[{"award-number":["601133461"]}]},{"name":"Dr. Miriam and Sheldon G. Adelson Center","award":["0601133671"],"award-info":[{"award-number":["0601133671"]}]},{"name":"Sylvan Adams Sports Institute","award":["347300-00"],"award-info":[{"award-number":["347300-00"]}]},{"name":"Sylvan Adams Sports Institute","award":["601133461"],"award-info":[{"award-number":["601133461"]}]},{"name":"Sylvan Adams Sports Institute","award":["0601133671"],"award-info":[{"award-number":["0601133671"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms241311142","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T01:41:36Z","timestamp":1688694096000},"page":"11142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Treatment-Resistant Depression (TRD): Is the Opioid System Involved?"],"prefix":"10.3390","volume":"24","author":[{"given":"Shaul","family":"Schreiber","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"},{"name":"Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"},{"name":"Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Keidan","sequence":"additional","affiliation":[{"name":"Sylvan Adams Sports Institute, Tel Aviv University, Tel Aviv 6905904, Israel"},{"name":"Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv 6905904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-339X","authenticated-orcid":false,"given":"Chaim G.","family":"Pick","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Sylvan Adams Sports Institute, Tel Aviv University, Tel Aviv 6905904, Israel"},{"name":"Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv 6905904, Israel"},{"name":"Dr. Miriam and Sheldon G. Adelson Chair and Center for the Biology of Addictive Diseases, Tel Aviv University, Tel Aviv 6905904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report","volume":"163","author":"Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0924-9338(02)00653-3","article-title":"Beyond the monoamine hypothesis: Mechanisms, molecules and methods","volume":"17","author":"Hindmarch","year":"2002","journal-title":"Eur. Psychiatry"},{"key":"ref_3","first-page":"167","article-title":"Treatment-resistant depression","volume":"80","author":"Little","year":"2009","journal-title":"Am. Fam. Physician"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0193-953X(23)00042-4","article-title":"The Individual and Societal Burden of Treatment-Resistant Depression: An Overview","volume":"46","author":"Jha","year":"2023","journal-title":"Psychiatr. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1001\/jamapsychiatry.2022.3860","article-title":"Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study","volume":"80","author":"Lundberg","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00004850-198807000-00007","article-title":"Current and historical concepts of opiate treatment in psychiatric disorders","volume":"3","author":"Weber","year":"1988","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/10550880802122646","article-title":"Psychotherapeutic benefits of opioid agonist therapy","volume":"27","author":"Peter","year":"2008","journal-title":"J. Addict. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104800","DOI":"10.1016\/j.neubiorev.2022.104800","article-title":"The opioid system in depression","volume":"140","author":"Jelen","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_9","unstructured":"White, W.L. (2014). Slaying the Dragon: The History of Addiction Treatment and Recovery in America, Chestnut Health Syst. Maryland (USA). [2nd ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1136\/rapm-2020-101924","article-title":"Rising opioid prescription fulfillment among non-cancer and non-elderly patients-Israel\u2019s alarming example","volume":"46","author":"Miron","year":"2021","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13584-023-00558-9","article-title":"Trends and correlated outcomes in population-level prescription opioid and transdermal fentanyl use in Israel","volume":"12","author":"Shapira","year":"2023","journal-title":"Isr. J. Health Policy Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Borsodi, A., Bruchas, M., Cal\u00f3, G., Chavkin, C., Christie, M.J., Civelli, O., Connor, M., Cox, B.M., Devi, L.A., and Evans, C. (2023). Opioid receptors in GtoPdb v.2023.1. IUPHAR\/BPS Guide Pharmacol. CITE, 2023.","DOI":"10.2218\/gtopdb\/F50\/2023.1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.2174\/138161209788168100","article-title":"Opiates as Antidepressants","volume":"15","author":"Berrocoso","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41380-018-0117-2","article-title":"Endogenous opioid system dysregulation in depression: Implications for new therapeutic approaches","volume":"24","author":"Karp","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1124\/jpet.109.159939","article-title":"Direct agonist activity of tricyclic antidepressants at distinct opioid receptor subtypes","volume":"332","author":"Onali","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0091-3057(99)00102-1","article-title":"Dopaminergic and opioidergic mediations of tricyclic antidepressants in the learned helplessness paradigm","volume":"64","author":"Besson","year":"1999","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1096\/fasebj.3.11.2673898","article-title":"5-hydroxytryptamine receptor \u201cfamilies\u201d","volume":"3","author":"Schmidt","year":"1989","journal-title":"FASEB J."},{"key":"ref_18","first-page":"8","article-title":"The role of receptor subtype diversity in the central nervous system","volume":"13","author":"Schofield","year":"1990","journal-title":"TINS"},{"key":"ref_19","unstructured":"Idzikiwski, C., and Cowen, P.J. (1991). Serotonin, Sleep and Mental Disorder, Wrightson Biomedical."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000406237","article-title":"Mianserin","volume":"18","author":"Pinder","year":"1982","journal-title":"Mod. Probl. Pharmacopsychiat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1600-0447.1983.tb00361.x","article-title":"Lack of anticholinergic and cardiovascular effects of mianserin; studies in healthy subjects and heart patients","volume":"67","author":"Kopera","year":"1983","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0924-977X(00)00069-9","article-title":"Effects of the co-administration of mirtazapine and paroxetine on serotonergic neurotransmission in the rat brain","volume":"10","author":"Besson","year":"2000","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_23","first-page":"19","article-title":"The pharmacologic profile of mirtazapine","volume":"57","year":"2000","journal-title":"J. Clin. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0924-977X(97)00088-6","article-title":"Interaction between the tetracyclic antidepressant Mianserin HCl and opioid receptors","volume":"8","author":"Schreiber","year":"1998","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2165\/00003495-198121060-00001","article-title":"Trazodone: A review of its pharmacological properties and therapeutic use in depression and anxiety","volume":"21","author":"Brogden","year":"1981","journal-title":"Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/0028-3908(80)90197-5","article-title":"Biochemical investigations into the mode of action of trazodone","volume":"19","author":"Robson","year":"1980","journal-title":"Neuropharmacology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/0028-3908(78)90094-1","article-title":"The development of cortical b-adrenoreceptor subsensitivity in the rat by chronic treatment with trazodone, doxepine and mianserin","volume":"17","year":"1978","journal-title":"Neuropharmacology"},{"key":"ref_28","first-page":"53","article-title":"Binding profile of trazodone and dapiprazole to same brain receptors","volume":"24","author":"Valeri","year":"1988","journal-title":"Drugs Exp. Clin. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"428B","DOI":"10.1097\/00002826-199202001-00831","article-title":"The profile of venlafaxine, a novel antidepressant agent, in behavioral antidepressant drug models","volume":"15 Pt B","author":"Lloyd","year":"1992","journal-title":"Clin. Neuropharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"435B","DOI":"10.1097\/00002826-199202001-00845","article-title":"The preclinical pharmacological profile of venlafaxine: A novel antidepressant agent","volume":"15 Pt B","author":"Moyer","year":"1992","journal-title":"Clin. Neuropharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4493","DOI":"10.1016\/0006-2952(86)90769-0","article-title":"Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohezanol derivative","volume":"35","author":"Muth","year":"1986","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/00004850-199503002-00003","article-title":"Pharmacologic profile and efficacy of venlafaxine","volume":"10","author":"Mendlewicz","year":"1995","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_33","first-page":"3030","article-title":"Venlafaxine: A heterocyclic antidepressant","volume":"51","author":"Ellingrod","year":"1994","journal-title":"Am. J. Hosp. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1S","DOI":"10.1097\/00004714-199606002-00001","article-title":"Synaptic effects of antidepressants","volume":"16","author":"Richelson","year":"1986","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2165\/00023210-199912010-00006","article-title":"Reboxetine","volume":"12","author":"Holm","year":"1999","journal-title":"CNS Drugs"},{"key":"ref_36","unstructured":"Bernstein, J.G. (1988). Handbook of Drug Therapy in Psychiatry, PSG Publishing Company. [2nd ed.]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1600-0447.1995.tb05920.x","article-title":"Clinical efficacy of reversible and selective inhibitors of monoamine oxidase A in major depression","volume":"91","author":"Paykel","year":"1995","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5140","DOI":"10.1007\/BF02246260","article-title":"Moclobemide: A range of opportunities","volume":"106","author":"Priest","year":"1992","journal-title":"Psychopharmacology"},{"key":"ref_39","unstructured":"Hofmann, F. (1994). Product Information, La Roche."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2165\/00003495-199200432-00003","article-title":"Pharmacological differences of serotonin reuptake inhibitors and possible clinical relevance","volume":"43","author":"Leonard","year":"1992","journal-title":"Drugs"},{"key":"ref_41","first-page":"343","article-title":"Not so selective serotonin reuptake inhibitors","volume":"59","author":"Stahl","year":"1998","journal-title":"J. Clin. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.euroneuro.2004.08.008","article-title":"The Senantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors","volume":"15","author":"Chen","year":"2005","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.euroneuro.2005.11.013","article-title":"From selective to highly-selective SSRIs: A comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram","volume":"16","author":"Schreiber","year":"2006","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s007020170047","article-title":"Pharmacotherapy of depression: A historical analysis","volume":"108","author":"Ban","year":"2001","journal-title":"J. Neural. Trans."},{"key":"ref_45","unstructured":"Nyro, G. (2023, May 20). Pszichiatria. Medicina 1962, Budapest. Available online: https:\/\/moly.hu\/konyvek\/nyiro-gyula-szerk-psychiatria."},{"key":"ref_46","first-page":"175","article-title":"A quantitative analysis of clinical drug trials for the treatment of affective disorders","volume":"129","author":"Davis","year":"1993","journal-title":"Psychopharmacol. Bull."},{"key":"ref_47","first-page":"3","article-title":"selection of pharmacological treatment of depressive illness, part two. Efficacy and differential activity of antidepressants","volume":"2","author":"Ban","year":"1999","journal-title":"Neuropsychopharmacol. Hung."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1515\/REVNEURO.1993.4.1.63","article-title":"The adrenergic-cholinergic imbalance hypothesis of depression: A review and a perspective","volume":"4","author":"Fritze","year":"1993","journal-title":"Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0741-8329(95)02038-1","article-title":"Naltrexone in the treatment of alcoholism: A clinical review","volume":"13","author":"Volpicelli","year":"1996","journal-title":"Alcohol"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s002130050969","article-title":"Resolution of treatment-refractory depression with naltrexone augmentation of paroxetine\u2014A case report","volume":"143","author":"Amiaz","year":"1999","journal-title":"Psychopharmacology"},{"key":"ref_51","first-page":"210","article-title":"Naltrexone in the treatment of alcohol dependence","volume":"28","author":"Wesley","year":"1994","journal-title":"Ann. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/0006-3223(94)91240-8","article-title":"The efficacy of naltrexone in preventing re-abuse of heroin after detoxification","volume":"35","author":"Shufman","year":"1994","journal-title":"Biol. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/1098-108X(199311)14:3<229::AID-EAT2260140302>3.0.CO;2-X","article-title":"A review of the controlled trials of pharmacotherapy and psychotherapy in the treatment of bulimia nervosa","volume":"143","author":"Mitchell","year":"1993","journal-title":"Int. J. Eat. Disord."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1097\/00004583-199307000-00025","article-title":"Naltrexone and fuoxetine in Prader-Willi syndrome","volume":"32","author":"Benjamin","year":"1993","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_55","first-page":"803","article-title":"Augmentation of morphine induced changes in brain monoamine metabolism after chronic naltrexone treatment","volume":"255","author":"Ahee","year":"1990","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.jpsychires.2023.03.037","article-title":"The efficacy and safety of buprenorphine for the treatment of depression: A systematic review and meta-analysis","volume":"161","author":"Riblet","year":"2023","journal-title":"J. Psychiatr. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0006-8993(96)01069-4","article-title":"Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with kappa3 analgesia","volume":"744","author":"Pick","year":"1997","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jpain.2022.09.013","article-title":"The Delta-Opioid Receptor Bidirectionally Modulates Itch","volume":"24","author":"Smith","year":"2023","journal-title":"J. Pain"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2174\/1570159043359477","article-title":"Buprenorphine: A unique drug with complex pharmacology","volume":"2","author":"Lutfy","year":"2004","journal-title":"Curr. Neuropharmacol."},{"key":"ref_60","first-page":"7067437221145013","article-title":"OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse. Effects of Buprenorphine\/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial","volume":"14","author":"Bastien","year":"2022","journal-title":"Can. J. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1192\/bjp.2018.196","article-title":"Repeated oral ketamine for ambulatory treatment of resistant depression. A randomized, double-blind, placebo-controlled proof-of-concept study","volume":"214","author":"Domani","year":"2019","journal-title":"Br. J. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/s41386-023-01577-5","article-title":"Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: Interim results of the SUSTAIN-3 study","volume":"48","author":"Zaki","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"173228","DOI":"10.1016\/j.pbb.2021.173228","article-title":"Opioid receptor system contributes to the acute and sustained antidepressant-like effects, but not the hyperactivity motor effects of ketamine in mice","volume":"208","author":"Zhang","year":"2021","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Faouzi, A., Varga, B.R., and Majumdar, S. (2020). Biased Opioid Ligands. Molecules, 25.","DOI":"10.3390\/molecules25184257"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0014-2999(80)90515-4","article-title":"Intrathecal morphine in mice: A new technique","volume":"67","author":"Hylden","year":"1980","journal-title":"Eur. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1385\/JMN:18:1-2:143","article-title":"Venlafaxine and mirtazapine: Different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects\u2014A possible opioid involvement in severe depression?","volume":"18","author":"Schreiber","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109501","DOI":"10.1016\/j.mehy.2019.109501","article-title":"Trazodone and Mirtazapine: A possible opioid involvement in their use (at low dose) for sleep?","volume":"136","author":"Schreiber","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.euroneuro.2009.06.004","article-title":"The antinociceptive properties of reboxetine in acute pain","volume":"19","author":"Schreiber","year":"2009","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_69","first-page":"349","article-title":"The antinociceptive effects of fluoxetine","volume":"9","author":"Schreiber","year":"1996","journal-title":"Pain Clin."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0924-977X(96)00031-4","article-title":"The antinociceptive effect of fluvoxamine","volume":"6","author":"Schreiber","year":"1996","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0304-3940(98)00638-7","article-title":"The antinociceptive effect of moclobemide in mice is mediated by noradrenergic pathways","volume":"253","author":"Schreiber","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0304-3940(99)00627-8","article-title":"The antinociceptive effect of venlafaxine in mice is mediated through opioid and adrenergic mechanisms","volume":"273","author":"Schreiber","year":"1999","journal-title":"Neurosci. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0166-4328(00)00185-6","article-title":"The antinociceptive effect of trazodone in mice is mediated through both m-opioid and serotonergic mechanisms","volume":"114","author":"Schreiber","year":"2000","journal-title":"Behav. Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0361-9230(02)00825-0","article-title":"The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms","volume":"58","author":"Schreiber","year":"2002","journal-title":"Brain Res. 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