Algorithm Guided Treatment Versus Treatment as Usual (TAU) for Patients With Treatment Resistant Depression

NCT ID: NCT07080723

Last Updated: 2025-07-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2027-06-30

Brief Summary

The trial utilizes a pragmatic, randomized, open label design with two parallel arms. Participants aged 18-65 with a diagnosis of unipolar depressive disorder and without stable remission in the past 12 months are randomized 1:1 to receive either algorithm guided treatment (AGT) or treatment as usual (TAU). The AGT approach incorporates pre-defined treatment steps, critical decision points, and "if-then" rules based on symptom response. It leverages prior treatment history, current symptomatology, and tolerability profiles to personalize the therapeutic sequence and reduce treatment inertia. In contrast, TAU reflects standard clinical practice, where treatment decisions are left to clinician discretion without algorithmic structure. The primary objective of the study is to determine whether AGT leads to a greater reduction in depressive symptoms over a 12-week treatment period, as measured by the 6-item Hamilton Depression Rating Scale (HAMD-6). Secondary objectives include evaluating cognitive and psychosocial functioning, suicide risk, treatment adherence, tolerability, number of medication changes, and long-term outcomes at a 24-week follow-up, providing insights into the longer-term trajectory of TRD management.

Detailed Description

The study period consists of 12 weeks in the randomized phase and 12-week extended follow up period during which all participants are monitored and treated at the clinician's discretion. After baseline, study visits are planned at 4, 8, 12 and 24 weeks.

Conditions

Treatment Resistant Depression (TRD)

Study Design

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

Study Groups

Algorithm guided treatment (AGT)

Treatment choice is defined in the AGT group by predetermined steps and critical decision points. The critical decision point moment is predetermined and marks the patient's outpatient visit. At these timepoint, HAMD score is determined and change from last visit is calculated, and based on this evaluation, specific treatment revisions are made following established "if-then" decision rules. This implies that the subsequent step is determined by the outcome of the assessment. If the patient's condition is assessed satisfactory, one step is selected and if the desired outcome is not achieved, an alternative step is pursued. Treatment choice for each step is based on patients medical history, previous therapy effect, adverse events, evidence based medicine and is selected a priori when patients are randomized by discussion with a senior consultant. AGT consists of which treatments to use at each step, how to implement each treatment and in what order to implement different treatments.

Group Type: EXPERIMENTAL

Algorithm guided treatment (AGT)

Intervention Type: OTHER

AGTs consist of strategies (which treatments to use), tactics (how to implement each treatment) and treatment steps (in what order to implement the different treatments). Furthermore, AGTs also define critical decision points during the treatment at which the effects of a certain treatment are assessed and based on this assessment recommend specific treatment revisions according to preset "if-then rules." This is most often done by implementing measurement-based care.

Treatment as usual (TAU)

TAU group treatment is defined and supervised by senior consultants with an experience in a treatment of patients with treatment resistant depression.

Group Type: ACTIVE_COMPARATOR

Treatment as usual (TAU)

Intervention Type: OTHER

TAU includes the standard clinical care for patients with TRD as determined by a senior consultant.

Interventions

Algorithm guided treatment (AGT)

AGTs consist of strategies (which treatments to use), tactics (how to implement each treatment) and treatment steps (in what order to implement the different treatments). Furthermore, AGTs also define critical decision points during the treatment at which the effects of a certain treatment are assessed and based on this assessment recommend specific treatment revisions according to preset "if-then rules." This is most often done by implementing measurement-based care.

Intervention Type: OTHER

Treatment as usual (TAU)

TAU includes the standard clinical care for patients with TRD as determined by a senior consultant.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. A diagnosis of unipolar depressive disorder according to ICD-10 based on documented completion of the Mini International Neuropsychiatric Interview, version 7.0.2 (MINI 7.0.2) at Screening and confirmed by medical records or a healthcare professional.

2. Have not achieved stable remission of depression in 12 months at investigator's clinical assessment.

3. Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).

4. Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.

5. Signed document of informed consent.

6. The participant is an outpatient.

7. No significant change in medical treatment in the last 4 weeks before screening visit.

8. The patient is pharmacologically treated for depression.

Exclusion Criteria

1. A diagnosis of dementia.

2. Substance misuse influencing study participation as judged by the investigator.

3. High risk of non-adherence at the investigator's discretion.

4. Not understanding the Danish language as judged by the investigator.

5. Suicidality according to C-SSRS with a positive response to question 4 or 5 within the last three months or upon investigator's discretion.

6. Medical conditions such as 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.

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

Sponsors

Aalborg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

René Ernst Nielsen

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

René Ernst Nielsen, Prof., MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Aalborg University Hospital, Psychiatry, Denmark

Locations

Aalborg University Hospital

Aalborg, , Denmark

Countries

Denmark

Central Contacts

Deni Rkman, MD

Role: CONTACT

deni.rkman@rn.dk

+4593856194

Simon Johansen, MsN

Role: CONTACT

simon.johnsen@rn.dk

+4561395631

Facility Contacts

Deni Rkman, MD

Role: primary

deni.rkman@rn.dk

+4593856194

Simon Johansen, MsN

Role: backup

simon.johnsen@rn.dk

+4561395631

Other Identifiers

N-20250007

Identifier Type: -

Identifier Source: org_study_id