Anhedonia, Depression
Conditions
Keywords
anhedonia, depression, dopamine, pramipexole
Brief summary
The purpose of the study is to assess the long-term efficacy and safety of add-on pramipexole for treatment of patients with anhedonic depression.
Detailed description
The heterogeneity of depression suggests that several different neurocircuits and pathophysiological mechanisms are involved. Anhedonia - the inability to experience pleasure from, or the lack of motivation to carry out, usually enjoyable activities - is a promising endophenotype within the depression spectrum, with a distinct pathophysiology involving dopaminergic mesolimbic projections. Anhedonia is common in depression and associated with treatment resistance. Pramipexole, an agonist to the dopamine -receptor 3, is an established treatment of Parkinson's disease. Based on its mechanism of action, pramipexole might be efficacious in a subtype of depression characterized by anhedonia and lack of motivation - symptoms linked to dopaminergic hypofunction. The aim of this open label follow-up study is to test the long-term efficacy and tolerability of add-on pramipexole in anhedonic depression. This is a continuation study of an RCT (EudraCT# 2022-001563-26) in which patients are randomized to either pramipexole or placebo for 9 weeks. After completion of the RCT, patients will be offered to participate in the current trial. Approximately 50% of the patients have been treated with pramipexole and 50% with placebo within the frames of the RCT. Patients randomized to pramipexole in the RCT will continue on their current dose and patients randomized to placebo will start pramipexole using the same dosing schedule as in the RCT. A total of 80 research subjects with unipolar depression, bipolar disorder in depressive phase, or dysthymia will be offered participation in the study after completing the RCT given that they fulfill all the inclusion criteria, and none of the exclusion criteria. Subjects have study visits once a month during 6 months, or more often if needed based on side effects. Symptom severity, side effects and ecological momentary assessments are recorded at each study visit and dose titration schedule is modified as needed. Between study visits, research subjects may contact study personnel and the investigators can quickly arrange for an additional study visit if needed. After the study, the decision to continue with pramipexole outside of the study or discontinue with pramipexole will be based on patient preference in combination with a willingness of the patient's regular physician to take over the treatment outside of the study.
Interventions
DRUGPramipexole
6 months of treatment with add-on Pramipexole
Sponsors
Region Skane
Lund University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Not masked.
Intervention model description
Within the frame of the previous RCT study (Eudra CT 2022-001563-26) approximately 50% of the participants have been treated with the study product and 50% with placebo. In this study all participants receive the study product, so some will continue their ongoing treatment with the study product and some will start using the study product.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Previous participation in RCT testing the short-term efficacy of pramipexole vs placebo (EudraCT# 2022-001563-26). * Study participants randomized to pramipexole in the RCT who wish to continue with their treatment can enrol in the study. * Study participants randomized to placebo in the RCT who continue to fulfil the inclusion criteria (and none of the
Exclusion criteria
) after the RCT can enrol in the study. * The research subject has given informed consent to participate in the study. Additional inclusion criterion for patients receiving placebo during the RCT * Anhedonia symptoms: 3 or 4 points on ≥ 3 items of the Snaith-Hamilton Pleasure Scale (SHAPS-C). This has been adopted in previous studies as a definition of "clinically significant anhedonia".
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anhedonia symptoms | Baseline | Total Snaith Hamilton Anhedonia Pleasure (SHAPS) self-report scale scores. Higher scores equal more severe anhedonoa. Score range 14-56 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core depression symptoms | baseline | Hamilton Depression Rating Scale-6 (HDRS6) scores (subscale of HDRS-17) |
| Ecological momentary assessments | baseline | Number of steps/day, movement pattern distribution over the day, walking distance, time spent in light, moderate and intense physical activity, resting heart rate, blood oxygen saturation, heart rate variability (stress scores), sleep latency (time to fall asleep), sleep awakening (how often you wake up during the night), wakefulness (time in minutes awake during a night), time in deep sleep, sleep efficiency (time asleep vs. total time in bed). All variables are measured using activity meters. |
| Anhedonic symptoms | baseline | Dimensional Anhedonia Rating Scale (DARS) total score |
| General depressive symptoms | baseline | Montgomery-Åsberg Depression Rating Scale (MADRS-S) |
| Sleep and insomnia | Baseline | Insomnia Severity Index (ISI) total score |
| Apathy symptoms | Baseline | Apathy Evaluation Scale (AES) total score |
| Anxiety symptoms | baseline | Generalized Anxiety Disorder 7-item scale (GAD-7) |
| Life quality | Baseline | Brunnsviken Brief Quality of life scale (BBQ) total score |
| Side effects | Baseline | Number and severity of adverse events |
| Cognitive symptoms | 6 months | Change in cognitive performance using the WAIS-IV, Repeatable Battery for the Assessment of Neuropsychological Status, Delis-Kaplan Executive Function System. |
Countries
Sweden
Outcome results
None listed