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

NCT05913947 | Recruiting Phase 4

• 1 other identifier: 2021-006706-69
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression, Bipolar

Outcome Measures

Primary Outcomes (1)

• Change 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).

  8 weeks

Secondary Outcomes (31)

• Difference-in-difference for HDS-17

  Week 4 and 8

• Difference-in-differences in HDS-6 for the PP 8 population

  8 weeks

• 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

  Week 4 and 8

• Between-groups difference in the proportion of patients with 'acceptable wellbeing'

  up to 8 weeks

Study Arms (2)

Lithium

EXPERIMENTAL

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

Drug: Lithium

Cariprazine

EXPERIMENTAL

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

Drug: Cariprazine

Interventions

Lithium 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.

Also known as: Litarex, ATC; N05AN01

Lithium

Cariprazine 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.

Also known as: Reagila, ATC: N05AX15

Cariprazine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aalborg University Hospital: lead
• Glostrup University Hospital, Copenhagen: collaborator
• Psychiatric Center Copenhagen, Rigshospitalet: collaborator
• Psychiatric Hospital, Hillerod: collaborator
• Mental Health Department Odense, University Clinic: collaborator

Study Sites (1)

Aalborg University Hospital

Aalborg, 9000, Denmark

RECRUITING

Related Publications (1)

• 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.

  PMID: 40866064 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium; lithium citrate; cariprazine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• René E. Nielsen, Prof, MD,PhD

  Psychiatry, Aalborg University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sanne V. Hovgesen, MD

CONTACT

+45 25487706; sanne.hovgesen@rn.dk

Simon Johnsen, MsN

CONTACT

+45 50589034; simonjohnsen@rn.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: June 22, 2023
• Study Start: December 13, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 2, 2028
• Last Updated: January 21, 2026

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)