Ireland
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Recruiting Phase 3

Dehydroepiandrosterone (DHEA) as Augmentation of Standard Antidepressants in Treatment-resistant Depression.

NCT07843927 · tracked via the Priya Life Science Germany tracker
Phase
Phase 3
Started
2026-06-22
Last updated
2026-09-28

Condition(s) studied

Treatment Resistant Depression (TRD)

Investigational drug(s) / intervention(s)

Dehydroepiandrosterone (DHEA) →Placebo

Dehydroepiandrosterone (DHEA): 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.

Placebo: Matching placebo capsules, indistinguishable from the investigational product, will be administered orally for 6 weeks as add-on treatment to continued standard antidepressant monotherapy.

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
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: * 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 * The patient meets the criteria for a dependency disorder in the M.I.N.I. for DSM-5 * The patient has dementia or moderate to severe cognitive impair-ment. Exclusion Criteria Related to IMP * The Patient is currently taking DHEA or has taken it within the last 14 days prior to screening visit. * The patients is currently taking hormone replacement therapy with sex hormones (other than contraceptives) * The patient has undiagnosed genital bleeding * The patient has untreated endometrial hyperplasia The patient has or has had sex hormone-dependent cancer (e.g. breast cancer, ovarian cancer, endometrial cancer, prostate can-cer) * The patient is allergic or has contraindication to DHEA or lactulose and cellulose * The patient has previous diagnosis of chronic kidney disease stage G3b (or higher) or GFR \< 30 ml/min. * The patient has diagnosis of prostatic hyperplasia. Exclusion Criteria Related to standard antidepressant medication (AxMP) * The Patient is taking antidepressants other than those listed as in-clusion criterion (SSRI, SNRI, tricyclic antidepressants, bupropion, mirtazapine) * The patient is taking psychotropic medication, e.g. antipsychotics, anticonvulsants, lithium or Johannis herbs. Allowed substances in-clude benzodiazepines, non-benzodiazepines (Zopiclon, Zolpidem or Eszopiclon) and antidepressants listed under inclusion criteria. * The patient is using non-selective, irreversible MAO inhibitors (e.g. tranylcypromine) or selective, reversible MAO-A inhibitors (e.g. moclobemide) or the reversible non-selective MAO inhibitor line-zolid * The patient has insulin-dependent diabetes mellitus General Safety Exclusion Criteria * The patient has an untreated and unstable general medical condi-tion (e.g. hypertension with end organ damage or hypertensive de-railment) * The patient has a medical history of liver failure and/or bilirubin above 3 times the normal range and reduced total protein * The patient is pregnant or breastfeeding. * The patient of childbearing age shows an unwillingness to use an effective contraceptive method (defined as a Pearl Index \< 1) * The patient currently has or has a history of venous thromboembo-lism (VTE) (deep vein thrombosis, pulmonary embolism) * The patient currently has or has a history of arterial thromboem-bolic disease (e.g. angina pectoris, myocardial infarction, stroke) * The patient has a thrombophilic disease (e.g. protein C, protein S or antithrombin deficiency) * The patient has porphyria * The patient has clinically significant untreated hypothyroidism * The patient has clinically significant abnormalities in the 12-lead ECG (e.g. prolongation of the QTc interval ≥ 500 ms) as performed during screening visit * The patient is a vulnerable person (defined as: persons deprived their liberty, confined to an institution by court or administrative or-der, persons that may have Insufficient power, intelligence, educa-tion, resources, strength, or other needed attributes to protect their own interests, or unable to explicitly give consent) * The patient might be dependent on representative of the sponsor, the investigator or the trial site The patient is currently participating in another interventional clini-cal trial. Laboratory Exclusion Criteria * The patient's laboratory values show clinically significant abnor-malities * The patient currently has liver disease with liver-specific levels out-side the age- and gender-specific reference intervals \[elevations of GOT or GPT above 3 times the upper normal value (ULN)\]

Primary outcome measure(s)

  • 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.

Trial sites (9)

FacilityCityRegionStatus
Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie Berlin State of Berlin Recruiting
Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Universität Augsburg Augsburg Germany Recruiting
Alexianer St. Hedwig Krankenhaus, Berlin Berlin Germany Recruiting
Universitätsklinikum Frankfurt, Klinik für Psychiatrie, Psychosomatik und Psychotherapie, Frankfurt Germany Recruiting
Klinik für Psychiatrie und Psychotherapie am Universitätsklinikum Freiburg Freiburg im Breisgau Germany Recruiting
Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Psychiatrie und Psychotherapie Hamburg Germany Recruiting
Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie Leipzig Germany Recruiting
Klinik für Psychiatrie und Psychotherapie am LMU Klinikum München Germany Recruiting
Helios Hanseklinikum Stralsund Klinik und Poliklinik für Psychiatrie Stralsund Germany Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07843927 on ClinicalTrials.gov ↗ ← All trials in Germany