Mechanism of the coadministration of antidepressants with dopamine partial agonist for treatment-resistant major depressive disorder.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Hokkaido University
• Principal Investigator: Kitaichi Yuji 北海道大学, 医学研究院, 客員研究員 (80374445)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脳内微小透析 / ドパミン / 側坐核 / ドパミン部分アゴニスト

Outline of Final Research Achievements

Combination of milnacipran, a serotonin noradrenailine reuptake inhibitor, and aripiprazole, a partial dopamine agonist, did not increase extracellular dopamine levels in the nucleus accumbens of rats, but significantly increase noradrenaline leves.Co-administration of sertraline with aripiprazole significantly decreased scores of forced swim test. Conversely, combination of low-dose aripiprazole and sertraline tended to higher score than high-dose aripiprazole. Co-administration of aripiprazole (3mg and 9mg) with sertraline prolonged immobility time.Pharmacological resluts were inconsistent with behavioral findeing.
We were preparing for clinical research, but due to covid-19, we decided to stop the clinical research considering the safety of subjects.

Free Research Field

精神薬理学

Academic Significance and Societal Importance of the Research Achievements

基礎研究の結果では、抗うつ薬とSSRI/SNRIによる抗うつ効果増強のメカニズムはそれぞれの抗うつ薬で異なった作用機序が関係している可能性が示唆された。臨床場面において、ドパミン部分アゴニストと併用に効果的な抗うつ薬の選択には、さらなる基礎研究の推進に加えて、うつ病患者さんによる臨床研究が今後重要と考えられた。