Efficacy and safety of 24-week pramipexole augmentation in patients with treatment resistant depression. A retrospective cohort study

Pramipexole is a dopamine agonist with potential antidepressant, neuroprotective, antioxidant and antiinflammatory activity. In the present study we investigated the 24 weeks effect and safety of traditional AD augmentation with pramipexole for treatment-resistant depression. The study includes 116 patients, 37 (32%) with bipolar disorders and 79 (68%) with major depressive disorder, who failed to respond to at least 2 ADs trials of different classes and that were treated with AD augmented with pramipexole. Mood stabilizers and/or second-generation antipsychotics were added in patients with bipolar or mixed depression. Exclusion criteria were psychotic depression, rapid cycling bipolar course and previous unsuccessful treatment with pramipexole. After 24 weeks of pramipexole augmentation (median max dose 1.05 mg/day, IQR 0.72-1.08) 74.1% of patients responded (>= 50% reduction of baseline Hamilton Depression Rating Scale21 total score) and 66.4% remitted (Hamilton Depression Rating Scale21 total score < 7). Global Assessment of Functioning score significantly increase from 53 (50-60) at baseline to 80 (71-81) at 24 weeks (Wilcoxon signed rank test = 8.174, p < 0.001]. Ten patients (8.6%) dropped out (8 due to side effects and 2 for lack of efficacy) and 1 experienced an induced hypomanic switch. No patient committed a suicide attempt, had suicidal ideation, needed hospitalization, reported lethargy, gambling, hypersexuality and compulsive shopping. The limitations of the study are the observational design, the lack of a control group, the inclusion of outpatients only, the unblinded outcomes assessment, and the flexibility of the add-on schedule. The findings of the present study showed that off-label use of pramipexole as augmentation of traditional AD is an effective and safe 24 weeks treatment of resistant unipolar and bipolar depression. These results need confirmation from randomized clinical trials on larger samples.