Clinical trial NCT05913947: Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)
Official title: Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression: a Pragmatic Head-to-head Open, Randomized Multicenter Study: The 9th Study of the Danish University Antidepressant Group (DUAG 9)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Depression, Bipolar
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Mental Health Center, Glostrup
name: Mental Health Center North Zealand
name: Mental Health Department Odense, University Clinic
name: Psychiatric Center Copenhagen, Rigshospitalet
First posted: 2023-06-22
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in Hamilton Depressions scale, version 6 (HDS-6)
timeFrame: 8 weeks
Secondary outcomes:
measure: Difference-in-difference for HDS-17
timeFrame: Week 4 and 8
measure: Difference-in-differences in HDS-6 for the PP 8 population
timeFrame: 8 weeks
measure: Between-groups difference in proportion of responders and remitters in HDS-6 Scores.
timeFrame: Week 4 and week 8
measure: Between-groups difference in proportion of responders and remitters
timeFrame: Week 4 and 8
measure: Between-groups difference in the proportion of patients with 'acceptable wellbeing'
timeFrame: up to 8 weeks
measure: Between-groups difference in proportion of switches to mania/hypomania.
timeFrame: up to 8 weeks
measure: Between-groups difference in "(switch to mania or hypomania) / (response) -ratio",
timeFrame: up to 8 weeks
measure: Between-group differences in reason for and time to all cause treatment discontinuation
timeFrame: up to 8 weeks
measure: Between-group difference in treatment compliance.
timeFrame: up to 8 weeks
measure: Between-group difference in reasons for premature discontinuation
timeFrame: up to 8 weeks
measure: Difference-in-difference for MAS
timeFrame: Week 4 and 8
measure: Difference-in-difference for MES
timeFrame: Week 4 and 8
measure: Difference-in-differences for MADRS
timeFrame: Week 4 and 8
measure: Difference-in-difference for YMRS
timeFrame: Week 4 and 8
measure: Difference-in-differences for ASRM-14
timeFrame: Week 4 and 8
measure: Difference-in-differences for MDI
timeFrame: Week 4 and 8
measure: Difference-in-differences for WHO-5 questionnaire
timeFrame: Week 4 and 8
measure: Difference-in-difference for SCIP
timeFrame: Week 8
measure: Difference-in-difference for COBRA
timeFrame: Week 8
measure: Difference-in-difference for FAST
timeFrame: Week 4 and 8
measure: Difference-in-difference for PSQI
timeFrame: Week 4 and 8
measure: Difference-in-difference for CGI-S
timeFrame: Week 4 and 8
measure: Difference-in-difference for CGI-I
timeFrame: Week 4 and 8
measure: Difference-in-difference for C-SSRS
timeFrame: Week 4 and 8
measure: Difference-in-difference for accumulated benzodiazepine dose
timeFrame: Up to 8 weeks
measure: Difference-in-difference for time to all-causes discontinuation
timeFrame: Up to 8 weeks
measure: Difference-in-difference for time to all-causes. all-causes study endpoint.
timeFrame: Up to 8 weeks
measure: Between-group difference in reasons for time to all cause discontinuation.
timeFrame: Up to 8 weeks
measure: Between-group difference in reasons for treatment expectation.
timeFrame: Up to 8 weeks
measure: Between-group difference in reasons for adverse events.
timeFrame: Up to 8 weeks
measure: Between-group difference in reasons for serious adverse events.
timeFrame: Up to 8 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
Study officials:
affiliation: Psychiatry, Aalborg University Hospital
name: René E. Nielsen, Prof, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: