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

NCT07080723 | Recruiting Phase 4

• 1 other identifier: N-20250007
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Treatment Resistant Depression (TRD)

Keywords

Algorithm guided treatment; AGT; ALGO; Treatment as usual; TAU; Treatment resistant depression; TRD; Depression

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Scale, 6 item version (HAMD-6)

  The primary outcome measure is the Hamilton Depression Scale, 6 item version (HAMD-6), used as a continuous variable. The primary outcome is the difference in differences (DID) between patients randomized to receive algorithm-guided treatment as compared to treatment as usual, as measured by HAMD-6, based on the mITT population. The 6-item version of the Hamilton Depression Rating Scale ranges from 0 to 22, with higher scores indicating a worse outcome.

  From baseline to end of study (12 weeks)

Secondary Outcomes (17)

• HAMD-17

  Up to 24 weeks

• HAMD-6

  Up to 24 weeks

• UKU

  Up to 24 weeks

• SCIP

  Up to 12 weeks

• FAST

  Up to 12 weeks

Study Arms (2)

Algorithm guided treatment (AGT)

EXPERIMENTAL

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.

Other: Algorithm guided treatment (AGT)

Treatment as usual (TAU)

ACTIVE COMPARATOR

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

Other: Treatment as usual (TAU)

Interventions

Algorithm guided treatment (AGT) 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.

Algorithm guided treatment (AGT)

Treatment as usual (TAU) OTHER

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

Treatment as usual (TAU)

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 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.
• Have not achieved stable remission of depression in 12 months at investigator's clinical assessment.
• 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.
• Signed document of informed consent.
• The participant is an outpatient.
• No significant change in medical treatment in the last 4 weeks before screening visit.
• The patient is pharmacologically treated for depression.

You may not qualify if:

• A diagnosis of dementia.
• Substance misuse influencing study participation as judged by the investigator.
• High risk of non-adherence at the investigator's discretion.
• Not understanding the Danish language as judged by the investigator.
• Suicidality according to C-SSRS with a positive response to question 4 or 5 within the last three months or upon investigator's discretion.
• 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.

Sponsors & Collaborators

• Aalborg University Hospital: lead

Study Sites (1)

Aalborg University Hospital

Aalborg, 9000, Denmark

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• René Ernst Nielsen, Prof., MD, PhD

  Aalborg University Hospital, Psychiatry, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deni Rkman, MD

CONTACT

+4593856194; deni.rkman@rn.dk

Simon Johansen, MsN

CONTACT

+4561395631; simon.johnsen@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: Clinical Professor

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 23, 2025
• Study Start: August 13, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)