Table 1

Study objectives (from https://www.isrctn.com/ISRCTN84666271)

ObjectivesOutcome measuresTime points
Primary objectivePrimary outcome
To compare the efficacy of pramipexole and placebo at 12 weeks postrandomisationImprovement (change from baseline) of depressive symptoms measured on the QIDS-SR16Week 1–12
Secondary objectivesSecondary outcomes
To compare the tolerability and safety of pramipexole and placebo during the 48-week treatment phaseTolerability assessed by:
  • Termination of trial treatment due to intolerance

  • Adverse reactions

  • TSQM-9


Safety–emergence of new symptoms:
  • ALTMAN (manic symptoms)

  • QUIP-RS (impulse control)

  • Suicidal ideation (QIDS-SR16)

Weeks 1–48
To compare the effect of pramipexole and placebo on reward sensitivityChange in reward sensitivity parameter from model fitted to learning/decision making task between baseline, week 2 and week 12Baseline, week 2, week 12
To test the degree to which change in reward sensitivity mediates the 12 weeks response to pramipexole of both depressive, and specifically anhedonic, symptomsChange in QIDS-SR16 and SHAPS scores between baseline and week 12 and change in reward sensitivity between baseline and week 2Baseline, week 2, week 12
To compare the extent to which an increase in reward sensitivity predicts therapeutic responseChange scores in the learning/decision making task at 2 weeks and the change in the QID-SR16 at 12 weeksWeek 2, week 12
To explore the extent to which reward sensitivity at baseline predicts therapeutic responseBaseline scores on the learning/decision making task and the change in QIDS-SR16 at 12 weeksBaseline, week 12
To explore the extent to which level of anhedonia at baseline predicts therapeutic responseBaseline scores on SHAPS and change in the QIDS-SR16 at 12 weeksBaseline, week 12
To compare the effect of pramipexole and placebo on the trajectory of symptoms of depressionQIDS-SR16 scores collected weekly across 48 weeks of the trialWeekly for week 1–48
To compare the effect of pramipexole and placebo on response and remission rates, using the QIDS-SR16 at twelve weeksQIDS-SR16 response, defined as a reduction of <50% of baseline scores at week 12, remission as a score of <5 at week 12Baseline, week 12
To compare the impact of pramipexole and placebo on symptoms of anhedonia, anxiety and clinician rated depressionChange scores for the SHAPS, GAD-7 and QIDS-C between baseline and week 12Baseline, week 12
To compare the impact of pramipexole and placebo on functional outcome over the 48 weeks of treatmentChange scores for the WSAS-screener between baseline and week 48Baseline, weeks 12, 24, 36 and 48
To determine the impact on quality of life and capability well-being of pramipexole relative to placebo over 48 weeksChange in the following over 48 weeks:
  • EQ-5D-5L

  • ICECAP-A

  • OxCAP-MH

Baseline, weeks 12, 24, 36 and 48
To examine the health/social care and broader societal costs of patients relative to placebo over 48 weeksChange in the following over 48 weeks:
  • HEQ

Baseline, weeks 12, 24, 36 and 48
  • GAD-7, General Anxiety Disorder Scale; HEQ, Health Economics Questionnaire; ICECAP-A, ICEpop capability measure for adults; OxCAP-MH, Oxford CAPabilities questionnaire-Mental Health; QIDS-SR16, quick inventory of depressive symptomatology self-report 16; QUIP-RS, Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease–Rating Scale; SHAPS, Snaith-Hamilton Pleasure scale; TSQM-9, Treatment Satisfaction Questionnaire for Medication Version 9; WSAS, Work and Social Adjustment Scale.