Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis

Abstract

Background: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson’s disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression. Methods: This comprehensive systematic review and meta-analysis of observational studies on pramipexole–antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint. Results: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8–69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects. Conclusions: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression.

Dopaminergic Changes in the Subgenual Cingulate Cortex in Dementia with Lewy Bodies Associates with Presence of Depression

“…Dopaminergic de cits including reduced striatal DAT binding has been observed in depressed patients with anhedonia 22 and additionally in PD and DLB, with DLB cases showing greater DAT loss in caudate compared to PD 52 , with reduced ACC DAT binding in DLB 53 . The use of dopamine agonists in MDD can have signi cant bene ts, and may be bene cial in DLB if suitable treatment regimens are identi ed 54,55 .…”

“…Our results indicate that reduced DRD3 levels may play a role in depression in DLB, and DRD3 speci c dopaminergic agents may be bene cial. Pramipexole and ropinirole improve depressive symptoms in PD and may provide bene t for depression in DLB, although careful monitoring may be needed to prevent unwanted side effects including impulse control disorders and hallucinations 54,66,67 . In PD, improved working and episodic memory occurs with dopamine agonists, indicating that dopaminergic agonists may additionally improve cognition 68,69 .…”

Dopaminergic Changes in the Subgenual Cingulate Cortex in Dementia with Lewy Bodies Associates with Presence of Depression

“…Reduced striatal DAT binding has been observed in depressed patients with anhedonia (Sarchiapone et al 2006), as well as in PD and DLB, with DLB cases showing more severe DAT loss in caudate compared to PD (Walker et al 2004) along with reduced ACC DAT binding in DLB (Marquie et al 2014). The use of dopamine agonists in treatment resistant depression is shown to have significant benefits and may have possible benefits in DLB if a suitable treatment regime can be found (Tundo et al 2023;Tundo, de Filippis, and De Crescenzo 2019).…”

Struggling Can Also Show on the Inside: Current Knowledge of the Impact of Childhood Maltreatment on Biomarkers in Mood Disorderss

“…However, dopamine receptor agonist also seems to have antidepressant effects in studies of major depressive disorder (MDD) and bipolar depression. 42…”