Long-term efficacy and tolerability of add-on pramipexole for anhedonic depression – an open label follow-up study

The primary objective of this study is to investigate the **efficacy** and tolerability of long-term add-on pramipexole in patients with anhedonic **depression**. This is clinically relevant as anhedonia, a core symptom of depression, often remains resistant to standard antidepressant treatments. Evaluating pramipexole, a dopamine agonist, could provide insights into alternative therapeutic strategies for managing this challenging aspect of depression.

The clinical trial focuses on individuals diagnosed with **depression**, specifically targeting those experiencing anhedonic symptoms. The study population includes both male and female participants, with an age range spanning from 18 to 64 years. Participants are generally in good health, excluding the presence of depression-related symptoms. The total number of participants is not specified, as the sponsor has not provided this information. Selection for the trial is contingent upon previous participation in a randomized controlled trial (RCT) assessing the short-term efficacy of pramipexole versus placebo. Participants who were randomized to pramipexole and wish to continue treatment, as well as those who received a placebo and meet specific criteria, are eligible to enroll. The trial does not include a vulnerable population, and lifestyle factors such as diet and physical activity are not highlighted as significant considerations for this study.

The clinical trial is designed to evaluate the long-term efficacy and tolerability of **pramipexole** as an add-on treatment for anhedonic depression. This study follows a randomized, open-label design and is a continuation for participants who were part of a previous randomized controlled trial (RCT) assessing the short-term efficacy of pramipexole versus placebo. The trial is expected to commence on January 16, 2023, and conclude by January 12, 2026, with a maximum treatment period of 25 weeks for each participant. The study involves the administration of pramipexole in the form of prolonged-release tablets, with a maximum daily dose ranging from 0.26 mg to 2.1 mg, and a total maximum dose of 3.15 mg, administered orally.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous participation in the RCT and informed consent. Follow-up visits will be scheduled to monitor the primary endpoint, which is the total score on the Snaith-Hamilton Pleasure Scale (SHAPS-C), and secondary endpoints, including HDRS6 scores, physical activity metrics, sleep parameters, and various psychological assessments. The end-of-study visit will assess the overall outcomes and any adverse events experienced during the trial.

Participant involvement is expected to last up to 25 weeks, with conditions for early termination including withdrawal of consent, significant adverse events, or non-compliance with the study protocol. The trial aims to provide comprehensive data on the long-term use of pramipexole in treating anhedonic depression, contributing valuable insights into its efficacy and safety profile.

The clinical trial involves the administration of **PRAMIPEXOLE**, a **prolonged-release tablet** formulated for **oral use**. The active substance, pramipexole, is of chemical origin and is utilized in the study to assess its efficacy and tolerability as an add-on treatment for anhedonic depression. The trial includes four different dosing regimens of pramipexole, each with a distinct maximum daily dose and a consistent maximum total dose over the treatment period.

The first dosing regimen of pramipexole involves a maximum daily dose of **0.26 mg**. The second regimen allows for a higher maximum daily dose of **2.1 mg**. The third regimen prescribes a maximum daily dose of **0.52 mg**, while the fourth regimen involves a maximum daily dose of **1.05 mg**. Despite the variations in daily dosing, all regimens maintain a consistent maximum total dose of **3.15 mg** over the treatment period. The maximum treatment period for each regimen is set at **25 days**.

Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The focus remains solely on evaluating the long-term efficacy and tolerability of pramipexole as an add-on therapy for anhedonic depression.

The efficacy of the clinical trial investigating the long-term use of **pramipexole** as an add-on treatment for anhedonic depression will be assessed using both primary and secondary endpoints. The primary endpoint for evaluating efficacy is the total score on the Snaith-Hamilton Pleasure Scale (SHAPS-C), which measures anhedonia symptoms. Secondary endpoints include a variety of measures such as HDRS6 scores, which assess depression severity, and several physical activity and sleep-related parameters, including the number of steps per day, movement pattern distribution, walking distance, and various sleep metrics like sleep latency and efficiency.

Additional secondary endpoints involve total scores from various scales such as the DARS, MADRS-S, Insomnia Severity Scale, AES, GAD-7, and BBQ, which evaluate different aspects of mental health and well-being. The trial will also monitor adverse events and side effects, and utilize fMRI, blood, and CSF biomarkers from the preceding RCT as potential treatment predictors. A comprehensive neuropsychological test battery, including WAIS-IV, RBANS, D-KEFS, CPT-3, and cognitive self-assessment PDQ-5, will be employed to assess cognitive function.