Treatment-resistant bipolar depression Mental and Behavioural Disorders Bipolar affective disorder
Conditions
Interventions
Current interventions as of 29/07/2022:
The pre-randomisation phase will allow patients to have their antipsychotics adjusted and mood stabiliser initiated if necessary. Once this is done, 290 parti
the trial is ‘double-blind’.
For all participants, initiation of trial treatment will follow a 4-week titration schedule starting at 0.25 mg/day in a single (oral) dose usually at night for 3 days.
Sponsors
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 29/07/2022: Stage 1/ pre-randomisation: 1. Currently under the care of secondary care mental health services at screening with a plan for the patient to remain in secondary care throughout the period of the trial 2. A decision made by the patient’s clinical team that a change in medication is indicated 3. A current diagnosis of Bipolar Disorder (type I or II), defined as in DSM-5, which is supported by the use of the Mini-International Neuropsychiatric Interview (MINI) 4. Currently depressed, i.e. meeting DSM-5 criteria for a Major Depressive Episode assessed via MINI and with a current QIDS-SR >10 5. Current episode of depression failed to have responded to adequate trials, or lack of tolerability or patient declined/clinically inappropriate, of two different NICE recommended medications (quetiapine, olanzapine (with or without fluoxetine), lamotrigine) or lurasidone. Adequacy of treatment trial defined using a custom-designed 'Bipolar Demographics and Treatment Questionnaire' (BDTQ). 6. Aged 18 years or over at the point of consent 7. Willing and able to provide written informed consent prior to any trial procedures taking place 8. In the opinion of the investigator, is able to follow the trial prescription instructions and is able to manage 8 weeks supply of trial medication without risk of overdose 9. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (ß-hCG)] 10. Women of child-bearing potential are required to use a highly effective contraceptive method during the pre-randomisation and post-randomisation phase of the trial. Highly effective methods of contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) - bilateral tubal occlusion - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) Stage 2/ at randomisation: 1. Been in Stage 1 (pre-randomisation) for a minimum of 23 calendar days. 2. Currently depressed, i.e. meeting DSM-5 (78) criteria for a Major Depressive Episode and with a current QIDS-SR >10. 3. A minimum of two telephone/teleconference or videoconference calls with a trial RA and two on-line weekly symptom ratings have been completed during the pre-randomisation phase 4. On mood stabilising medication (lithium, valproate, carbamazepine, lamotrigine) 5. If on an antipsychotic this must be one listed, and at a dose of no more than the maximum stated, in the table in section 4.1. 6. All regular psychotropic medication, including antipsychotics and mood stabilisers, at a stable dose for a minimum of four weeks. Additionally, if a participant is on lamotrigine, quetiapine, olanzapine or lurasidone then this must have been at the current dose or higher for a minimum of three m
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 29/07/2022: Stage 1/ pre-randomisation: 1. DSM-5 defined severe substance use disorder. 2. Current psychotic symptoms as assessed using the MINI. 3. History of retinal disease. 4. Current cardiovascular symptoms or significant concerns around cardiovascular disease. 5. History of significant renal disease (for example within the last 6 months eGFR is less than 50ml/min/1.73m2 or there is a concern that eGFR is deteriorating and may be expected to fall below 50 during the course of the study). 6. Any known sensitivity to trial drug including its excipients. 7. Current pregnancy or planned pregnancy during the trial period, or breastfeeding. 8. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 9. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 10. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by a sleep clinic). 11. Significant clinical concern regarding impulse control behaviours Stage 2/ at randomisation: 1. Psychotic symptoms over the preceding 4 weeks. 2. Any known sensitivity to trial drug including its excipients 3. Any deterioration in physical or mental health since pre-randomisation that means there is a clinical concern to proceed with the study. 4. Current or planned pregnancy during the trial period, or breast feeding. 5. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 6. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 7. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by a sleep clinic). 8. Significant clinical concern regarding impulse control behaviours 9. Electroconvulsive therapy (ECT) in the last 28 days. 10. Any study team’s concern regarding the patient’s ability to remain engaged in the study collecting self-ratings of their symptoms and undertake all study procedures. _____ Previous exclusion criteria as of 20/05/2020: Stage 1/ pre-randomisation: 1. DSM-5 defined severe substance use disorder. 2. Current psychotic symptoms as assessed using the MINI. 3. History of retinal disease. 4. Current cardiovascular symptoms or significant concerns around cardiovascular disease. 5. History of significant renal disease (for example within the last 6 months eGFR is less than 50ml/min/1.73m2 or there is a concern that eGFR is deteriorating and may be expected to fall below 50 during the course of the study). 6. Any known sensitivity to trial drug including its excipients. 7. Current pregnancy or planned pregnancy during the trial period, or breastfeeding. 8. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 9. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 10. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Depression symptoms measured using QIDS-SR questionnaire (Quick Inventory of Depressive Symptomatology) at 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 12/10/2020: 1. Mood and anxiety symptoms over 48 weeks, and pleasure symptoms over 12 weeks, measured using the QIDS-SR questionnaire weekly to week 48, the Generalised Anxiety Disorder 7 (GAD-7) weekly to week 48 and the Snaith Hamilton Pleasure Scale (SHAPS) at weeks 0, 6 and 12 2. Psychosocial function measured using the Work and Social Adjustment Scale (WSAS) at weeks 0, 6, 12, 24, 36 and 48 3. Tolerability of pramipexole assessed using rates of AEs, SAEs and SUSARs reported describing severity, seriousness, causality and expectedness 4. Risk of switching to mania and occurrence of psychosis or impulse control disorders, which are known possible side-effects of pramipexole, measured using the Altman Self Rating Scale of Mania (ASRM) questionnaire completed weekly to week 48 5. Rates of impulsivity during treatment with pramipexole, measured using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease – Rating Scale (QUIP-RS) at weeks 0, 6, 12 and then 4-weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) 6. Side effects and overall acceptability of pramipexole treatment measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) at Weeks 6, 12 and then 4-weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) and collection of Adverse Events - reported weekly to week 12 and then 4-weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) 7. Adherence to medication to which patients are randomised via participant reported dose taken during RA phone calls and from central trial medication accountability and reconciliation records 8. Quality of life assessed using EuroQoL 5 Dimension 5 Level (EQ-5D-5L) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 9. Capability assessed using the ICEpop CAPability measure for Adults (ICECAP-A) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 10. Capability in people with mental health problems | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactZoë;Nicola Walmsley;Goudie
;
Outcome results
None listed