Treatment resistant depression Mental and Behavioural Disorders
Conditions
Interventions
In addition to their standard antidepressant medication, participants will be randomised 1:1 to receive either Pramipexole dihydrochloride monohydrate or a matched placebo. Randomisation will be via m
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Once informed consent has been given, participants will enter a run-in phase prior to randomisation. Inclusion criteria for entry to run-in phase: 1. Willing and able to give informed consent to participate in the trial 2. Age 18 years or over 3. Diagnosis of DSM-V major depression 4. Quick Inventory of Depressive Symptomatology self-report version (QIDS-SR16) score >10 (moderate, severe or very severe depression) 5. Currently taking and tolerating antidepressant medication 6. Lack of response to at least 2 antidepressants at therapeutic doses (based on Maudsley Prescribing Guidelines and/or British National Formulary) in the current episode 7. Indication for change in treatment 8. Willing to continue an antidepressant treatment 9. Negative urine pregnancy test result (in females of child-bearing potential only) Inclusion criteria for entry to randomised phase: 1. Verbal consent to randomisation 2. QIDS-SR16 score >10 3. On a stable dose of an antidepressant for at least 4 weeks
Exclusion criteria
Exclusion criteria: Exclusion criteria for entry to run-in phase: 1. Diagnosis of current or previous psychosis, bipolar disorder or Parkinson’s Disease 2. Current antipsychotic medication 3. Clinically significant current or previous impulse control difficulties 4. Serious suicide or homicide risk 5. Current treatment with any medication known to interfere with pramipexole metabolism including cimetidine, memantine and methyldopa 6. Contraindications to pramipexole including history of or current treatment for eye disease, significant, symptomatic cardiovascular or renal disease or significant, symptomatic orthostatic hypotension 7. Previous course of pramipexole (>2 weeks duration) 8. Untreated or unstable medical condition which, in the judgement of the investigator, could interfere with the safety of receiving pramipexole or ability to complete the trial 9. Female and pregnant, lactating or planning pregnancy 10. Female of child-bearing potential not willing to use effective contraception Exclusion criteria for entry to randomised phase: 1. eGFR (from screening blood test) < 50 mL/min/1.73m2 2. Psychotherapy started in past 4 weeks or planned to start within next 12 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement (change from baseline) of depressive symptoms measured on the Quick Inventory of Depressive Symptomatology, self-report version (QIDS-SR16) measured at baseline and 12 weeks post-randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety (emergence of new symptoms) and Tolerability during the 48 week randomised phase assessed by: 1.1 Termination of trial treatment due to intolerance 1.2 Adverse reactions 1.3 TSQM 1.4 ALTMAN (manic symptoms) 1.5 QUIP-RS (impulse control) 1.6 Suicidal ideation (QIDS-SR16) 2. Change in reward sensitivity parameter from model fitted to learning/decision making task between baseline, week 2 and 12 weeks 3. Change in QIDS-SR16 and SHAPS scores between baseline and week 12 and change in reward sensitivity between baseline and week 2 4. Change scores in the learning/decision making task at 2 weeks and the change in the QID-SR16 at 12 weeks 5. Baseline scores on the learning/decision making task and the change in QIDS-SR16 at 12 weeks 6. Baseline scores on the SHAPS and change in the QID-SR16 at 12 weeks 7. QIDS-SR16 scores collected weekly across 48 weeks of the trial 8. QIDS-SR16 response, defined as a reduction of =50% in baseline score by week 12. QIDS-SR16 remission defined as a score of =5 at week 12 9. Change scores for the SHAPS, GAD-7 and QIDS-C between baseline and week 12 10. Change scores for the WSAS-screener between baseline and week 48 11. Change in: EQ-5D-5L, ICECAP-A, and OxCAP-MH over 48 weeks 12. HEQ information and costs over 50 weeks (2 weeks prior to randomisation and 48 weeks during the randomised phase) 13. Qualitative interviews with selected participants and investigators | — |
Countries
England, United Kingdom
Contacts
Public ContactAlex Lewis
Outcome results
None listed