Safety and tolerance of combination of monoamine oxidase inhibitors and direct dopamine agonists in adults and older adults with highly resistant depression.

Dopamine (DA) is likely to be involved in some depressive dimensions, such as anhedonia and amotivation, which account for a part of treatment-resistant forms. Monoamine oxidase inhibitors (MAOI) and direct D2 and D3 receptors agonists (D2/3r-dAG) are known to help, but we lack safety data about their combined usage. We report on safety and tolerance of the MAOI+D2r-dAG combination in a clinical series. All patients referred to our recourse center for depression between 2013 and 2021 were screened to select those who did receive the combo. Data were extracted from clinical files. Sixteen patients of 60±17 years of age (8 women, 7 with age>65years, all suffered from treatment resistant depression, 7 with bipolar disorder) received the combo. There were no life-threatening adverse effects (AE). However, AE were reported by 14 patients (88%) most of which were mild and consisted of insomnia, nausea, nervousness, confusion, impulse control disorder and/or "sleep attacks". One patient presented a serious AE requiring a short hospitalization for confusion. Intolerance led to failure to introduce treatment in two patients (13%). The retrospective non-interventional design, the variety of molecules, and the modest sample size limited the scope of these results. There was no life-threatening safety issue in combining MAOI and D2/3r-dAG, especially regarding cardiovascular side effects. The systematic screening of AE might account for their frequency, but these precluded the treatment in only two patients. Comparative studies are needed to assess the efficacy of this new combination.

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