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.
Patient provided written informed consent
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)
Exclusion Criteria Related to psychiatric diagnosis
The patient has current clinically significant suicidal ideation with intent, corresponding to a score of 4 or 5 for ideation on the C-SSRS, or a suicidal attempt within the past 6 months, as indicated by the C-SSRS at screening visit
The patient fulfills the criteria for psychotic depression according to DSM-5
The patient meets the criteria for schizophrenia, schizoaffective disorder or bipolar disorder in M.I.N.I according to DSM-5
Parallel
Dehydroepiandrosterone (DHEA)
DrugDehydroepiandrosterone (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.
Placebo
DrugMatching placebo capsules, indistinguishable from the investigational product, will be administered orally for 6 weeks as add-on treatment to continued standard antidepressant monotherapy.
Change score in MADRS (Montgomery-Asberg-Depression Rating Scale)
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.
MADRS response and remission
MADRS response (defined as 50 % MADRS score reduction) MADRS remission (defined as MADRS score \< 10)
Adverse event-related treatment discontinuation
Number and proportion of participants who discontinue study treatment due to an adverse event. Unit of Measure: Number and percentage of participants
Immunometabolic Changes
Change from baseline to Week 6 in C-reactive protein (CRP) concentration. Unit of Measure: mg/L
Immunometabolic Changes (2)
Change from baseline to Week 6 in interleukin-6 (IL-6) concentration. Unit of Measure: pg/mL
Number and proportion of participants experiencing adverse events
AEs) and serious adverse events (SAEs) during the 6-week treatment period. Unit of Measure: Number and percentage of participants
Quality of life assessed with EQ-5D-3L
Change from baseline to Week 6 in health-related quality of life as assessed using the EQ-5D-3L. The EQ-5D-3L index value will be derived according to the prespecified scoring algorithm.
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