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

Not Applicable

Not yet recruiting

• Conditions: Treatment Resistant Depression (TRD)

• Registration Number: NCT07080723
• Lead Sponsor: Aalborg University Hospital

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.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-07-07
• Study First Submitted QC: 2025-07-21
• Last Update Submitted: 2025-07-21
• Study First Posted: 2025-07-23
• Last Update Posted: 2025-07-23
• Study Start: 2025-08-01
• Primary Completion: 2027-06
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Hamilton Depression Scale, 6 item version (HAMD-6)	From baseline to end of study (12 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
COBRA	Up to 12 weeks	Difference in difference in Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA). Values range from 0 to 48, higher scores indicating a worse outcome.
Between-group differences in reason for all cause treatment discontinuation	Up to 24 weeks	Between-group differences in reason for all cause treatment discontinuation (lack of effect, lack of tolerability, lost to follow-up, or other cause)
Between-group differences in time to all cause treatment discontinuation	Up to 24 weeks	Between-group differences in time to all cause treatment discontinuation
Between-group differences in number of changes in the number of different prescribed medications over the treatment period	Up to 12 weeks	Between-group differences in number of changes in the number of different prescribed medications over the treatment period
Between-group difference for the ITT population in adverse events and serious adverse events	Up to 12 weeks	Between-group difference for the ITT population in adverse events and serious adverse events
Between-group difference for the ITT population in reasons for premature discontinuation	Up to 24 weeks	Between-group difference for the ITT population in reasons for premature discontinuation
Between-group difference for the ITT population in reasons for time to all cause discontinuation	Up to 24 weeks	Between-group difference for the ITT population in reasons for time to all cause discontinuation
HAMD-6	Up to 24 weeks	Difference-in-difference in HAMD-6 for the PP12 and the PP24 population. The 6-item version of the Hamilton Depression Rating Scale ranges from 0 to 22, with higher scores indicating a worse outcome.
CGI	Up to 12 weeks	Difference in difference in the Clinical Global Impression Scale (CGI). Values range from 1 to 7, higher scores indicating a worse outcome.
Between-group differences in number of changes in treatment strategies	Up to 12 weeks	Between-group differences in number of changes in treatment strategies
HAMD-17	Up to 24 weeks	All secondary outcomes are based on the mITT population unless otherwise specified. A Per Protocol (PP) analysis at 12 weeks and at the end of follow-up is performed for all continuous secondary outcomes.; Difference-in-difference in HAMD-17. The 17-item version of the Hamilton Depression Rating Scale ranges from 0 to 52, with higher scores indicating a worse outcome.
FAST	Up to 12 weeks	Difference-in-difference in the Functioning Assessment Short Test (FAST). Values range from 0 to 72, higher scores indicating a worse outcome).
UKU	Up to 24 weeks	Difference in difference in UKU adverse events scale
SCIP	Up to 12 weeks	Difference-in-difference in Screen for Cognitive Impairment in Psychiatry (SCIP).; Values range from 0 to 64+, higher scores indicating a better outcome.
C-SSRS	Up to 12 weeks	Difference in difference in the Columbia-Suicide Severity Rating Scale (C-SSRS).; Values range from 1 to 5, higher scores indicating a worse outcome.
Between-groups difference in proportion of responders and remitters in HAMD-6 score	Week 8 and 12	Responders are defined as subjects with a reduction of at least 50 % in their HAMD-6 scores between baseline and the endpoint of interest. Remitters are defined as subjects with HAMD-6 score below 5 at the endpoint of interest. Both are measured at 8 weeks or at a premature endpoint before last-observation-carried-forward (LOCF) and at 12 weeks or at a premature endpoint before LOCF.
Between-groups difference from original randomization in proportion of responders and remitters at end of follow-up	Up to 24 weeks	Between-groups difference from original randomization in proportion of responders and remitters at end of follow-up

Trial Locations

Locations (1)

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark