Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)

NCT ID: NCT05913947

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-13
• Study Completion Date: 2028-09-02

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.

Conditions

Depression, Bipolar

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lithium

Lithium citrate from 12 mmol increased to result in af 12-hour se-lithium between 0.6 and 0.8 mmol/l

Group Type: EXPERIMENTAL

Lithium

Intervention Type: DRUG

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.

Cariprazine

Cariprazine from 1.5 mg to 3 mg daily in a single dose.

Group Type: EXPERIMENTAL

Cariprazine

Intervention Type: DRUG

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.

Interventions

Lithium

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.

Intervention Type: DRUG

Cariprazine

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.

Intervention Type: DRUG

Other Intervention Names

Litarex, ATC; N05AN01; Reagila, ATC: N05AX15

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mental Health Center, Glostrup

UNKNOWN

Sponsor Role: collaborator

Mental Health Department Odense, University Clinic

UNKNOWN

Sponsor Role: collaborator

Psychiatric Center Copenhagen, Rigshospitalet

UNKNOWN

Sponsor Role: collaborator

Psychiatric Hospital, Hillerod

OTHER

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

René Ernst Nielsen

MD, PhD, Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

René E. Nielsen, Prof, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Psychiatry, Aalborg University Hospital

Locations

Aalborg University Hospital

Aalborg, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Sanne V. Hovgesen, MD

Role: CONTACT

sanne.hovgesen@rn.dk

+45 25487706

Simon Johnsen, MsN

Role: CONTACT

simonjohnsen@rn.dk

+45 50589034

Facility Contacts

Sanne V. Hovgesen, MD

Role: primary

sanne.hovgesen@rn.dk

+45 29217805

Simon Johnsen

Role: backup

simon.johnsen@rn.dk

+45 61395631

References

Hovgesen SV, Licht RWW, Straszek SPV, Christensen AE, Vinberg M, Videbech P, Miskowiak KW, Johnsen S, Munk MM, Mai ML, Baethge C, Kessing LV, Nielsen RE. Lithium versus cariprazine in the acute phase treatment for depressive episodes in patients with bipolar disorder: a protocol for a pragmatic open, randomised multicentre study - the 9th trial of the Danish University Antidepressant Group, DUAG-9. BMJ Open. 2025 Aug 27;15(8):e102406. doi: 10.1136/bmjopen-2025-102406.

Reference Type: DERIVED

PMID: 40866064 (View on PubMed)

Other Identifiers

2021-006706-69

Identifier Type: -

Identifier Source: org_study_id