Pramipexole as a Targeted Adjunctive Treatment for Anhedonia in Depression: Results From an Exploratory Pilot Study
Year: 2025
Type: conference-abstract
Abstract: Background Anhedonia is a common persisting state among depressed patients, associated with treatment resistance and increased loss of function. There are currently no specific and effective treatments for anhedonia. Previous trials have indicated that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed for clinical implementation. Given its mechanism of action, pramipexole might be efficacious for a depression subtype characterized by significant anhedonia and lack of motivation, symptoms associated with dopaminergic hypofunction. Aims and Objectives The objective was to investigate feasibility and target engagement of high dose, add on pramipexole treatment in anhedonic depression, as well as exploring biomarkers as predictors of treatment response, using a transdiagnostic design and several indicators of treatment efficacy. Method Twelve patients with unipolar or bipolar, moderate to severe depression, and significant anhedonia were included in this open label pilot study. All patients were on a stable dose of antidepressants and or mood stabilizers and received ten weeks of adjunctive pramipexole titrated to a maximum dose of 4,5 mg salt per day. Patients were rated with the Dimensional Anhedonia Rating Scale, the Montgomery Asberg Depression Rating and the Snaith Hamilton Pleasure Scale. Pre and post treatment analyses of high sensitivity C reactive protein were performed. Related Samples Wilcoxon signed rank test was used to investigate changes in symptom severity and hsCRP. Eight patients underwent fMRI pre and post treatment, and the monetary incentive delay task was used to investigate the effect on striatal activity during reward anticipation. Results DARS, MADRS and SHAPS scores all improved significantly over ten weeks of pramipexole treatment, p under 0,01. Mean levels of hs CRP decreased significantly over the course of treatment from mean 3,56 mg per litre at baseline to 2,61 mg per litre at endpoint, p under 0,01. There were significant treatment associated increases in reward related activity in several brain areas including the right lateral putamen, anterior left caudate, left posterior putamen, right dorsal caudate, left anterior putamen, and the right nucleus accumbens. Discussion and Conclusion This is the first study to suggest efficacy and target engagement of pramipexole in anhedonic depression and these preliminary findings could help inform future large-scale randomized controlled trials to test predictors of treatment response, advancing the field of precision psychiatry. References 1.Howland 2008 2.Argyropoulos and Nutt 2013 3.Pelizza and Ferrari A 2009 4.Uher et al 2012 5.Barone et al 2010 6.Tundo et al 2019 7.Fawcett et al 2016 8.Treadway et al 2019
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,693
OpenAlex ID: W4407417795