Silexan® in mild to moderate major depressive disorder

Trial details

Who runs it

Dr. Willmar Schwabe GmbH & Co. KG

Trial code

EU 2025-521744-37-00

Record updated

2026. november 10.

Original description

To demonstrate superiority of 80 mg/day Silexan® once daily vs placebo with respect to the change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score between Baseline and Week 8 when treating Major Depressive Disorders (MDD) of mild to moderate severity, regardless of adherence to the treatment regime and under the hypothetical condition that treatments which ease depressive symptoms are not available for participants who discontinue from the randomised treatment.Read full original descriptionShow less

Multi-centre, double-blind, placebo-controlled, randomised trial to prove the efficacy and safety of Silexan® (WS®1265) in patients with a major depressive episode of mild to moderate severity

To demonstrate superiority of 80 mg/day Silexan® once daily vs placebo with respect to the change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score between Baseline and Week 8 when treating Major Depressive Disorders (MDD) of mild to moderate severity, regardless of adherence to the treatment regime and under the hypothetical condition that treatments which ease depressive symptoms are not available for participants who discontinue from the randomised treatment.

If this can be shown, the superiority of 80 mg/day Silexan® compared to placebo should be demonstrated for treating MDD of mild depressive disorders based on the treatment effects described above.

In order to supplement the primary objective and to describe the clinical relevance of the findings, MADRS responder and remission rates are compared between Silexan® 80 mg/day and placebo for participants with MDD of mild to moderate severity and for participants with MDD of mild severity, regardless of adherence to the treatment regime and under the hypothetical condition that treatments which ease depressive symptoms are not available for participants who discontinue from the randomised treatment. Participants with a reduction of the MADRS total score of at least 50% between Baseline and Week 8 are responders, participants with an MADRS total score of less than 10 points at Week 8 are remitters.

Inclusion: Age of at least 18 years; Diagnosis of a major depressive episode according to ICD-10 (single episode: F32.0, 32.1, recurrent episode: F33.0, 33.1) of mild to moderate severity with a duration of at least 2 weeks but not longer than one year; MADRS total score for the inclusion in the run-in and into the active treatment phase: 17–30; Outpatient treatment by a general or specialised physician; Body weight: Body Mass Index (BMI) between 18 and 35 kg/m2; Written informed consent in accordance with the legal requirement; Readiness and ability on the part of the participant to comply with the physician’s instructions and to fill in the self-assessment scales.

Exclusion: Participation in a further clinical trial at the same time or in the last 12 weeks before screening; Any clinically important psychiatric or neurological diagnoses according to ICD-10, other than trial indication, within 6 months before the trial such as: • Schizophrenia (F20.-), • Acute anxiety disorder (F41.-) • Episodes of depression with any characteristics of a psychotic nature (F32.3, F33.3), depressive disorders not defined as inclusion criteria (F34.1, F32.9), bipolar disorder (F31.-), cyclothymia (F34.0), mania (F30.-), • Organic, including symptomatic, mental disorders (F00-F09), • Post-traumatic stress disorder (F43.10), • Eating disorders (F50.-); Risk of suicide, or previous suicide attempt or clear display of auto-aggressive behaviour as defined (but not limited to) MADRS Item 10 “suicidal thoughts” score  2; Lack of response to any adequate antidepressant therapy in the present episode of depression (adequate means  150 mg amitriptyline-equivalents per day or SSRI treatment during at least 6 weeks). Patients who are already well adjusted to an antidepressant therapy in the present episode may not be enrolled into this trial; Any of the following treatments within 30 days before baseline visit: • Antidepressants • Depot neuroleptics • Monoamine oxidase (MAO) inhibitors •Pimozide •Benzodiazepines •Other psychotropic drugs •Intravenous methylene blue •Linezolid; Unacceptability to discontinue or likelihood to need medication during the trial that is prohibited as concomitant treatment (see section 10.2). The following medication is not allowed during the trial: • Any psychotropic drugs including o benzodiazepines, tranquilizer, antidepressants, anxiolytics, antiepileptics, MAO inhibitors, pimozide, lamotrigine, linezolid, intravenous methylene blue o non-benzodiazepines (exception: ≤ 10 mg zolpidem/day for not longer than 10 days during the trial) o neuroleptics (exception: ≤ 75 mg melperone/day for not longer than 10 days during the trial). However, NO exception for zolpidem and for melperone is allowed within 5 days prior to any trial visit. • Long-term prophylactic treatment (e.g. lithium, carbamazepine) • Central-acting antihypertensive medication (guanethidine, guanoxan, clonidin, prazosine, α-methyldopa, reserpine) • Digoxin • Xanthine derivatives such as Theophylline • Antiparkinson medication • Phytopharmaceuticals with anxiolytic properties (e.g. hypericum extract, valerian extract) • Muscle relaxants • Analgesics of opiate type • Anaesthetics • Barbiturates • Nootropics • Coumarin derivates • Antibiotics; Non-medicinal psychiatric treatment during the last 2 weeks prior to baseline visit and during the course of the trial (e.g. standardised and digital psychotherapy, sleep withdrawal, phototherapy, electroconvulsive therapy, digital health applications [DiGAs]); Any unstable acute medical disorder or clinically relevant hepatic, renal, cardiovascular, respiratory, cerebrovascular, metabolic disorder or progressive diseases as cancer, haematologic diseases (including haemophilia, Christmas disease, von Willebrand’s disease, past medical history of bleeding gastric or duodenal ulcers or other significant bleeding disorders) or thyroid insufficiency (exception: non-insulin dependent diabetes mellitus, thyroid and anterior pituitary insufficiency on stable treatment), epilepsy or a history of seizure disorder or treatment with anticonvulsants for epilepsy or seizures, Parkinson’s disease; Any somatic disease that necessitates regular treatment with systemic steroids; Gastrointestinal disorders with uncertain absorption of orally administered drugs (e.g. partial or total gastrectomy, enterectomy, inflammatory bowel disease, celiac disease, symptomatic lactose intolerance, other disorders associated with chronic diarrhoea); History of hypersensitivity to lavender preparations and/or known allergies to the IMP, placebo or excipients; Any abnormal baseline finding considered by the investigator to be indicative of conditions that might affect trial results; Clinically significant abnormality of ECG and/or laboratory value(s) assessed at Screening Visit; Unable to read, understand and/or complete questionnaires; Diagnosis of MDD of severe severity as defined by ICD-10 (single episode: F32.2, recurrent episode: F33.2) or rating of the MADRS total score > 30 at screening or baseline visit; History or suspicion of unreliability, poor cooperation or non-compliance with medical treatment; History or evidence of alcohol and/or substance abuse or dependence, particularly of sedatives, hypnotics and anxiolytics. (F10-F19); Positive pregnancy test during Visit 1; Pregnancy, planning of pregnancy or lactation; Persons capable of childbearing if not using highly effective contraception; these include: • Oral, intravaginal, transdermal combined (oestrogen and progestogen containing) hormonal contraception • Oral, injectable and implantable progestogen-only hormonal contraception • Intrauterine device • Intrauterine hormone-releasing system • Bilateral tubal occlusion • Vasectomised partner • Sexual abstinence (referring to heterosexual relationships).

EU CTIS 2025-521744-37-00