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

Aalborg University Hospital

Status and phase: Not yet enrolling; Phase 4

Conditions: Treatment Resistant Depression (TRD)

Treatments: Other: Treatment as usual (TAU); Other: Algorithm guided treatment (AGT)

Study type: Interventional

Funder types: Other

Identifiers

NCT07080723

N-20250007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Algorithm guided treatment (AGT)

Experimental group

Description:

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.

Treatment:

Other: Algorithm guided treatment (AGT)

Treatment as usual (TAU)

Active Comparator group

Description:

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

Treatment:

Other: Treatment as usual (TAU)