Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)
- Registration Number
- NCT05913947
- Lead Sponsor
- Aalborg University Hospital
- Brief Summary
The goal is to study the effect of lithium compared to cariprazine in patients with depression in a bipolar disease.
The main question it aims to answer is:
Difference in change between the two groups from baseline to after 8 weeks treatment on Hamilton Ratings Scale for Depression, 6-item version (HDS-6)
Participants will be randomized to treatment with either lithium or cariprazin.
* Will meet for interview and ratings 4 times during study period.
* In two meetings, there will be made blood samples and ECG. At one meeting also a Urine sample.
* Will be contacted for telephone interviews at 6 occasions.
- Detailed Description
The primary aim is to investigate whether cariprazine is superior to lithium or vice versa in the acute treatment of patients with bipolar type 1 or 2 in a current depressive episode measured as change on the Hamilton Depression Scale, 6 item version (HDS-6) from baseline to 8 weeks of treatment. Secondarily, we aimed at comparing the two study medications on various other clinically relevant variables.
These include depressive and manic symptomatology, sleep patterns, general well-being, cognitive function, social functioning and suicidal ideation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 122
- A diagnosis of bipolar disorder, type 1 or type 2, and a current episode of depression according to DSM-5
- Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).
- No start or dose increase of psychotropic medication (except for benzodiazepines and benzodiazepine-like drugs (zopiclone, zolpidem, and melatonin)) in the two weeks prior to inclusion.
- No new start of formalized psychotherapy sessions, excluding psychoeducation, during the 4 weeks prior to inclusion.
- Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.
- The duration of the current depressive episode must be between 4 and 52 weeks as judged by the investigator at the time of randomization.
- Clinical uncertainty regarding which of the alternatives, cariprazine and lithium, would be the better choice in the specific case.
- Female participants should be sterile or non-fertile or, in case of being fertile, they must have a negative pregnancy test AND use safe anticonception.
- Signed document of informed consent.
- Prior or ongoing acute treatment of a depressive episode lasting > 14 days with either lithium or cariprazine as judged by the investigator.
- ECT within the current depressive episode.
- A score of MAS > 6.
- A diagnosis of dementia.
- High risk of non-adherence at the investigator's discretion.
- Not understanding the Danish language as judged by the investigator
- Psychiatric coercion in the form of forced admission or detainment OR sentence to forensic psychiatric care.
- Presence of clinically relevant delusions, hallucinations or other psychotic symptoms as judged by the investigator.
- Suicidality according to C-SSRS with a positive response to question 4 or 5 or upon investigator's discretion.
- Medical conditions like cancer, kidney failure, epilepsy, deep brain stimulation device, or other medical conditions interfering with study the outcome and safety as judged by investigator's discretion.
- Current harmful use or dependency of alcohol or drugs according to DSM-5.
- Known allergy to any of the substances in the study medication.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lithium Lithium Lithium citrate from 12 mmol increased to result in af 12-hour se-lithium between 0.6 and 0.8 mmol/l Cariprazine Cariprazine Cariprazine from 1.5 mg to 3 mg daily in a single dose.
- Primary Outcome Measures
Name Time Method Change in Hamilton Depressions scale, version 6 (HDS-6) 8 weeks The primary aim is to investigate whether cariprazine is superior to lithium or vice versa in the acute treatment of patients with bipolar type 1 or 2 in a current depressive episode measured as change on the Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
- Secondary Outcome Measures
Name Time Method Difference-in-difference for MES Week 4 and 8 Difference-in-differences for secondary continuous measures: MES Bech-Rafaelsens Melancholia scale, MES .(Values 0- 44, higher scores mean a worse outcome).
Difference-in-differences for MADRS Week 4 and 8 Difference-in-differences for secondary continuous measures: MADRS Montgomery-Aaberg Depression Rating Scale, MADRS .(Values 0- 60, higher scores mean a worse outcome).
Difference-in-difference for HDS-17 Week 4 and 8 Difference-in-differences for secondary continuous measures: Hamilton Depression Scale, 17 item version, HDS-17. (Values 0- 52, higher scores mean a worse outcome)
Difference-in-differences in HDS-6 for the PP 8 population 8 weeks Difference-in-differences (baseline to 8 weeks) in HDS-6 for the PP 8 population.
Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).Between-groups difference in proportion of responders and remitters Week 4 and 8 Between-groups difference in proportion of responders and remitters with response and remission defined by HDS-6 score without clinical relevant manic symptoms (MAS \<7) at planned or premature endpoint.
Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).Between-groups difference in "(switch to mania or hypomania) / (response) -ratio", up to 8 weeks Between-groups difference in "(switch to mania or hypomania) / (response) -ratio", defined as the number of subjects switching to mania or hypomania (as defined above) divided by the total number of responders, including those responders switching to mania
Between-group differences in reason for and time to all cause treatment discontinuation up to 8 weeks Between-group differences in reason for and time to all cause treatment discontinuation (lack of effect, lack of tolerability, lost to follow-up, or other cause).
Between-group difference in treatment compliance. up to 8 weeks Between-group difference in treatment compliance. Treatment compliance is defined as the proportion of received treatments out of the planned until drop-out or end of study.
Between-group difference in reasons for premature discontinuation up to 8 weeks Between-group difference for the ITT population in reasons for premature discontinuation
Difference-in-difference for MAS Week 4 and 8 Difference-in-differences for secondary continuous measures: MAS Bech-Rafaelsens Mania scale .(Values 0- 44, higher scores mean a worse outcome).
Between-groups difference in proportion of responders and remitters in HDS-6 Scores. Week 4 and week 8 Between-groups difference in proportion of responders and remitters at week 4 and 8 in HDS-6 scores.
Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).Between-groups difference in the proportion of patients with 'acceptable wellbeing' up to 8 weeks Between-groups difference in the proportion of patients with 'acceptable wellbeing', defined as the subject reporting ≥50 on the WHO-5 questionnaire at endpoint. WHO-five Well-being Index, WHO-5 (Values 0- 100, higher scores mean a better outcome).
Between-groups difference in proportion of switches to mania/hypomania. up to 8 weeks Between-groups difference in proportion of switches to mania/hypomania with or without mixed features, defined as mania/hypomania after DSM-5 or symptoms requiring treatment (switch or response occurring at any time in the study period)
Difference-in-difference for YMRS Week 4 and 8 Difference-in-differences for secondary continuous measures:YMRS Young Mania Rating Scale, YMRS .(Values 0- 60, higher scores mean a worse outcome).
Difference-in-differences for ASRM-14 Week 4 and 8 Difference-in-differences for secondary continuous measures:ASRM-14 Altman Self-Rating Mania Scale-14, .(Values 0- 56, higher scores mean a worse outcome).
Difference-in-differences for MDI Week 4 and 8 Difference-in-differences for secondary continuous measures:MDI Major Depression Inventory, MDI (Values 0- 58, higher scores mean a worse outcome).
Difference-in-differences for WHO-5 questionnaire Week 4 and 8 Difference-in-differences for secondary continuous measures: WHO-5 questionnaire.
WHO-five Well-beeing Index, WHO-5 (Values 0- 100, higher scores mean a better outcome).Difference-in-difference for SCIP Week 8 Difference-in-differences for secondary continuous measures: SCIP Screen for Cognitive Impairment in Psychiatry, SCIP (Values 0- 64+, higher scores mean a better outcome)
Difference-in-difference for COBRA Week 8 Difference-in-differences for secondary continuous measures: COBRA Cognitive complaints in bipolar disorder Ratings assessment, COBRA, (Values 0- 48, higher scores mean a worse outcome).
Difference-in-difference for FAST Week 4 and 8 Difference-in-differences for secondary continuous measures: FAST Functioning Assessment Short Test, FAST (Values 0 - 72, higher scores mean a worse outcome).
Difference-in-difference for PSQI Week 4 and 8 Difference-in-differences for secondary continuous measures:PSQI PIttsburgh Sleep Quality Index, PSQI (Values 0 - 21, higher scores mean a worse outcome).
Difference-in-difference for CGI-S Week 4 and 8 Difference-in-differences for secondary continuous measures: CGI-S Clinical Global Impression Scale - Severity, CGI-S (Values 1 -7, higher scores mean a worse outcome).
Difference-in-difference for CGI-I Week 4 and 8 Difference-in-differences for secondary continuous measures:CGI-I Clinical Global Impression Scale - Global Improvement CGI- I (Values 1 -7, higher scores mean a worse outcome).
Difference-in-difference for C-SSRS Week 4 and 8 Difference-in-differences for secondary continuous measures: C-SSRS Columbia-Suicide Severity Rating Scale, C-SSRS (Values 1 - 5, higher scores mean a worse outcome).
Difference-in-difference for accumulated benzodiazepine dose Up to 8 weeks Difference-in-differences for secondary continuous measures: accumulated benzodiazepine dose as diazepam equivalents (DSKP)
Difference-in-difference for time to all-causes discontinuation Up to 8 weeks Difference-in-differences for secondary continuous measures: for time to all-causes discontinuation
Difference-in-difference for time to all-causes. all-causes study endpoint. Up to 8 weeks Difference-in-differences for secondary continuous measures: all-causes study endpoint.
Between-group difference in reasons for time to all cause discontinuation. Up to 8 weeks Between-group difference for the ITT population in reasons for time to all cause discontinuation.
Between-group difference in reasons for treatment expectation. Up to 8 weeks Between-group difference for the ITT population in reasons for treatment expectation.
Between-group difference in reasons for adverse events. Up to 8 weeks Between-group difference for the ITT population in reasons for adverse events.
Between-group difference in reasons for serious adverse events. Up to 8 weeks Between-group difference for the ITT population in reasons for serious adverse events.
Trial Locations
- Locations (1)
Aalborg University Hospital
🇩🇰Aalborg, Denmark