Add-on pramipexole for anhedonic depression: study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden.

INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study. METHODS AND ANALYSIS: Eighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05355337 and NCT05825235.

Feasibility of completing Multidimensional Dyspnea Profile and Dyspnea-12 over the telephone in patients with oxygen-dependent disease.

BACKGROUND: Breathlessness is prevalent in severe disease and consists of different dimensions that can be measured using the Multidimensional Dyspnea Profile (MDP) and Dyspnea-12 (D-12). We aimed to evaluate the feasibility of MDP and D-12 over telephone interviews in oxygen-dependent patients, compared with other patient-reported outcomes (modified Medical Research Council (mMRC) and Chronic Obstructive Pulmonary Disease Assessment Test (CAT)) and with completion by hand. METHODS: Cross-sectional, telephone study of 50 patients with home oxygen therapy. Feasibility was assessed as completion time (self-reported by patients and measured), difficulty (self-reported) and help required to complete the instruments (staff). Completion time was compared with mMRC and CAT, and feasibility was compared with completion by hand in cardiopulmonary outpatients (n=182). Feasibility by age and gender was analysed using logistic regression. RESULTS: Of 136 patients approached, 50 (37%) participated (mean age: 72±10 years, 66% women). Completion times (in minutes) were relatively short for MDP (self-reported 6 (IQR 5-10), measured 8 (IQR 6-10)) and D-12 (self-reported 5 (IQR 3-8), measured 3 (IQR 3-4)), and slightly longer than mMRC (median 1 (IQR 1-1)) and CAT (median 3 (IQR 2-5)). Even though the majority of patients required no help, more assistance was required by older patients. Compared with patients reporting by hand, completion over the telephone required somewhat longer time and more assistance. CONCLUSION: Many patients with severe oxygen-dependent disease were unable or unwilling to assess symptoms over the telephone. However, among those able to participate, MDP and D-12 are feasible to measure multiple dimensions of breathlessness over the telephone.