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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
122
The starting dose (day one) of lithium citrate is 12 mmol (one tablet of lithium citrate contains 6 mmol lithium) given once a day before bedtime. On day three the dose is increased to 18 mmol. Dose adjustments are permitted after 7 days in a flexible manner to result in a 12-hour se-lithium between 0.6 and 0.8 mmol/l, aiming for the upper limit at the treating physician's discretion.
The starting dose for cariprazine is 1.5 mg daily in a single dose, and subsequently, after a minimum of two weeks, the dose can be increased to 3 mg and decreased again to 1.5 mg daily at the treating physician's discretion.
Aalborg University Hospital
Aalborg, Denmark
RECRUITINGChange in Hamilton Depressions scale, version 6 (HDS-6)
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).
Time frame: 8 weeks
Difference-in-difference for HDS-17
Difference-in-differences for secondary continuous measures: Hamilton Depression Scale, 17 item version, HDS-17. (Values 0- 52, higher scores mean a worse outcome)
Time frame: Week 4 and 8
Difference-in-differences in HDS-6 for the PP 8 population
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).
Time frame: 8 weeks
Between-groups difference in proportion of responders and remitters in HDS-6 Scores.
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).
Time frame: Week 4 and week 8
Between-groups difference in proportion of responders and remitters
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).
Time frame: Week 4 and 8
Between-groups difference in the proportion of patients with 'acceptable wellbeing'
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).
Time frame: up to 8 weeks
Between-groups difference in proportion of switches to mania/hypomania.
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)
Time frame: up to 8 weeks
Between-groups difference in "(switch to mania or hypomania) / (response) -ratio",
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
Time frame: up to 8 weeks
Between-group differences in reason for and time to all cause treatment discontinuation
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).
Time frame: up to 8 weeks
Between-group difference in treatment compliance.
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.
Time frame: up to 8 weeks
Between-group difference in reasons for premature discontinuation
Between-group difference for the ITT population in reasons for premature discontinuation
Time frame: up to 8 weeks
Difference-in-difference for MAS
Difference-in-differences for secondary continuous measures: MAS Bech-Rafaelsens Mania scale .(Values 0- 44, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-difference for MES
Difference-in-differences for secondary continuous measures: MES Bech-Rafaelsens Melancholia scale, MES .(Values 0- 44, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-differences for MADRS
Difference-in-differences for secondary continuous measures: MADRS Montgomery-Aaberg Depression Rating Scale, MADRS .(Values 0- 60, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-difference for YMRS
Difference-in-differences for secondary continuous measures:YMRS Young Mania Rating Scale, YMRS .(Values 0- 60, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-differences for ASRM-14
Difference-in-differences for secondary continuous measures:ASRM-14 Altman Self-Rating Mania Scale-14, .(Values 0- 56, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-differences for MDI
Difference-in-differences for secondary continuous measures:MDI Major Depression Inventory, MDI (Values 0- 58, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-differences for WHO-5 questionnaire
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).
Time frame: Week 4 and 8
Difference-in-difference for SCIP
Difference-in-differences for secondary continuous measures: SCIP Screen for Cognitive Impairment in Psychiatry, SCIP (Values 0- 64+, higher scores mean a better outcome)
Time frame: Week 8
Difference-in-difference for COBRA
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).
Time frame: Week 8
Difference-in-difference for FAST
Difference-in-differences for secondary continuous measures: FAST Functioning Assessment Short Test, FAST (Values 0 - 72, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-difference for PSQI
Difference-in-differences for secondary continuous measures:PSQI PIttsburgh Sleep Quality Index, PSQI (Values 0 - 21, higher scores mean a worse outcome).
Time frame: Week 4 and 8
Difference-in-difference for CGI-S
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).
Time frame: Week 4 and 8
Difference-in-difference for CGI-I
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).
Time frame: Week 4 and 8
Difference-in-difference for C-SSRS
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).
Time frame: Week 4 and 8
Difference-in-difference for accumulated benzodiazepine dose
Difference-in-differences for secondary continuous measures: accumulated benzodiazepine dose as diazepam equivalents (DSKP)
Time frame: Up to 8 weeks
Difference-in-difference for time to all-causes discontinuation
Difference-in-differences for secondary continuous measures: for time to all-causes discontinuation
Time frame: Up to 8 weeks
Difference-in-difference for time to all-causes. all-causes study endpoint.
Difference-in-differences for secondary continuous measures: all-causes study endpoint.
Time frame: Up to 8 weeks
Between-group difference in reasons for time to all cause discontinuation.
Between-group difference for the ITT population in reasons for time to all cause discontinuation.
Time frame: Up to 8 weeks
Between-group difference in reasons for treatment expectation.
Between-group difference for the ITT population in reasons for treatment expectation.
Time frame: Up to 8 weeks
Between-group difference in reasons for adverse events.
Between-group difference for the ITT population in reasons for adverse events.
Time frame: Up to 8 weeks
Between-group difference in reasons for serious adverse events.
Between-group difference for the ITT population in reasons for serious adverse events.
Time frame: Up to 8 weeks
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