Treatment Resistant Depression (TRD)
Conditions
Keywords
Algorithm guided treatment, AGT, ALGO, Treatment as usual, TAU, Treatment resistant depression, TRD, Depression
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.
Interventions
OTHERAlgorithm 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.
OTHERTreatment as usual (TAU)
TAU includes the standard clinical care for patients with TRD as determined by a senior consultant.
Sponsors
Aalborg University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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-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 treatment strategies | Up to 12 weeks | Between-group differences in number of changes in treatment strategies |
| 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 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 |
| 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-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 |
Countries
Denmark
Contacts
CONTACTDeni Rkman, MD
CONTACTSimon Johansen, MsN
PRINCIPAL_INVESTIGATORRené Ernst Nielsen, Prof., MD, PhD
Aalborg University Hospital, Psychiatry, Denmark
Outcome results
None listed