Treatment Resistant Depression (TRD)
Conditions
Keywords
TRD, DHEA, MDD
Brief summary
Major depressive disorder (MDD) is a major contributor to impaired health worldwide. Initial antidepressant treatment of MDD does not lead to response in up to 50 % of patients. TRD (Treatment Resistant Depression) is associated with increased rates of recurrence, mortality as well as increased treating costs compared to MDD. Treatment op-tions for TRD remain limited with lithium, quetiapine and esketamine being the only recommended and approved augmentation strategies in the EU. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, is a promising, safe and tolerable adjunctive treatment op-tion. DHEA has been meta-analytically shown to elicit antidepressant effects and to be safe both in MDD and for depressive symptoms in other medical diseases. However, previous RCTs (Randomized con-trolled trial) were small and no study has yet tested the antidepressant potential of adjunct treatment with DHEA in patients with TRD. Primary objective To determine whether add-on 100 mg/d DHEA to continued standard antidepressant medication improves depression to a greater extent than add-on placebo in subjects with treatment-resistant depression. Secondary objectives To determine whether add-on 100 mg/d DHEA to continued standard antidepressant medication improves response rates, remission rates, patients' impression of change, clinician's impression of severity and change, quality of life, social functioning and self-report depression se-verity to a greater extent than adjunct placebo in subjects with TRD. Furthermore, changes in glucose, glycosylated hemoglobin (HbA1c), total, HDL- and LDL-cholesterol, C-reactive protein (CRP), and inter-leukin-6 levels from baseline to week 6 will be determined.
Interventions
Dehydroepiandrosterone (DHEA) will be administered orally at a fixed dose of 100 mg/day for 6 weeks as add-on treatment to continued standard antidepressant monotherapy. Standard antidepressant medication will be continued at an unchanged dose throughout the treatment period.
DRUGPlacebo
Matching placebo capsules, indistinguishable from the investigational product, will be administered orally for 6 weeks as add-on treatment to continued standard antidepressant monotherapy.
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient provided written informed consent -,The patient is capable of giving consent (has sufficient knowledge of German and clearly understands the nature, significance and scope, including risks, of the medical procedure) * The patients is aged between 18 and 75 years (≥ 18 and ≤ 75) * The patient has an episode of major depression according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edi-tion) * The patient has treatment-resistant depression (TRD), defined as non-response to at least one 4-week antidepressant treatment trial (including the current treatment) in the index episode (correspond-ing to level 1 resistance to treatment failure according to the Maudsley staging method) * The patient has a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 20 * The patient is receiving antidepressant medication (SSRI or SNRI or tricyclic antidepressant or mirtazapine or bupropion) for at least 4 weeks, the dosage is at least at the approved minimum thera-peutic dosage and has been unchanged for at least 14 days prior to screening visit. * The patient had less than three (\<3) treatment attempts with anti-depressants in the current MDE (current treatment attempts not in-cluded).
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change score in MADRS (Montgomery-Asberg-Depression Rating Scale) | 6 weeks | The MADRS is a rating scale to measure depression severity. Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where higher MADRS scores indicate higher levels of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MADRS response and remission | 6 weeks | MADRS response (defined as 50 % MADRS score reduction) MADRS remission (defined as MADRS score \< 10) |
| Adverse event-related treatment discontinuation | 6 weeks | Number and proportion of participants who discontinue study treatment due to an adverse event. Unit of Measure: Number and percentage of participants |
Countries
Germany
Contacts
CONTACTChristian Otte, MD
CONTACTDeniz Yildirim Dogan, MD
STUDY_DIRECTORChristian Otte, MD
Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Berlin, Berlin 12203
Outcome results
None listed