Recruiting

Pharmacologic Treatment Augmentation in Chronic Depression

ClinicalTrials.gov IDNCT06410599

PhasePHASE2

Enrollment60

SponsorUniversity Hospital Tuebingen

Age18 Years

SexALL

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Conditions studied

Major Depressive Disorder

About this study

To enroll in this clinical trial, prospective participants must meet stringent criteria. The participants need to fall within the age range of 18 to 64 and exhibit chronic depression at therapy resistance stage 2. This stage signifies that the participants have undergone unsuccessful treatment with at least two different antidepressants, despite adequate dosage and duration. Moreover, the participants should have engaged in at least 12 sessions of psychotherapy without experiencing significant relief from depressive symptoms. Additionally, participants must demonstrate the cognitive capacity to provide informed consent. Upon expressing interest in the study and consenting to participate, individuals undergo a thorough screening process. This screening encompasses a comprehensive clinical interview to assess medical and psychiatric history, as well as various medical tests. These tests include physical examinations, blood draws (which may include pregnancy tests for female participants), and electrocardiograms (ECGs) to evaluate heart function. Following the screening, participants are randomly assigned to one of three different treatment groups (Ketamine +TAU; Ketamine+CBASP, Placebo+CBASP). The study protocol involves a combination of psychotherapeutic treatment and either ketamine infusions or placebo. Throughout the study period, participants are subject to regular data collection, including psychological assessments, blood samples, and magnetic resonance imaging (MRI) scans. Participants' responses to treatment, as well as any changes in symptoms or side effects, are closely monitored. After completing the study, participants are offered follow-up therapy as part of standard care. MRI scans are conducted to examine changes in brain activity associated with treatment response and depressive symptomatology, particularly focusing on alterations in neural circuitry and thought processes. Additionally, participants are encouraged to report any changes in medication regimen or other treatments received during the study period.

Interventions

Drug: Ketamine — Two ketamine hydrochloride (Ketamin Inresa 2 ml) infusions (interval 2-3 days) per week for three weeks, 6 infusions in total. Ketamine hydrochloride (Ketamin Inresa 2 ml) is applied continuously over a time span of 40 minutes with a subanesthetic dosage of 0.5 mg per kg body weight.
Drug: Placebo — Two times placebo (Isotone E NaCL 0.9 %) infusions (interval 2-3 days) per week for three weeks, 6 infusions in total. Placebo is applied continuously over a time span of 40 minutes.
Behavioral: CBASP — In addition to standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements, patients in the CBASP conditions receive one CBASP group session (50 min) per week for 12 weeks. The single sessions (one 50 min and one 25 min per week) contents are CBASP-specific.
Behavioral: TAU — Standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements.

Primary outcomes

Change of depressive symptoms assessed with Montgomery-Åsberg Depression Rating Scale (MADRS) between start and end of treatment in a group comparison (3 months after enrollment)

Eligibility information

Inclusion Criteria: * Age: 18 to 64 years at the time of study inclusion. * Diagnosis of chronic depression: recurrent depressive disorder, severe or moderate episodes (no full remission between the episodes according to DSM-IV-TR (Falkai et al., 2015) \[no distinct depressive symptoms for at least two months\]) or acute depressive episode lasting two or more years * Treatment resistance stage 2 according to (Thase and Rush, 1997): Patient's symptoms fulfil the criteria of chronic depression listed above even after at least two appropriate treatment attempts with two antidepressant medicaments from two different effect categories * Patient's symptoms fulfil the criteria of chronic depression listed above even after executing at least 12 sessions of psychotherapeutic treatment (psychoanalysis, depth psychology-based psychotherapy or cognitive behaviour therapy) * Understand and voluntarily sign an informed consent document prior to any study related assessments/ procedures. * Able to adhere to the study visit schedule and other protocol requirements. * Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact from study start until 28 days after the last infusion. * Males must agree to use a latex condom during any sexual contact with FCBP from the first infusion until 65 days after the last infusion, even if the person has undergone a successful vasectomy to refrain from donating semen or sperm from the first infusion until 65 days after the last infusion. * All subjects must agree to refrain from donating blood from the first infusion until 28 days after last infusion. * All subjects must agree not to share medication. Exclusion Criteria: * Acute substance misuse as primary diagnosis (assessed by the Structured Clinical Interview for DSM-V (SKID, Wittchen et al., 1997)) * Neurologic disorders: Stroke, cerebral ischemia, tumor, cerebral infection, autoimmune disease (according to clinical interview) * Disorders with increase of intracranial pressure, e. g. due to head injury (according to clinical interview) * Circulatory disturbance in the brain (according to clinical interview) * Pregnant or lactating females * Participation in any clinical study or having taken any investigational therapy, which would interfere with the study's primary end point * Epilepsy (according to clinical interview) * History of hypersensitivity to an investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product (according to clinical interview) * Pre-treatment with ketamine hydrochloride (Ketamin Inresa 2 ml) and/ or - CBASP (according to clinical interview) * Not or insufficiently treated hypertonia (subject will be excluded if repeated measures (3 times/ day) show values greater than 150 mmHg systolic or 100 mmHg diastolic blood pressure or if a lifetime diagnosis of hypertonia is reported) * Not or insufficiently treated hyperthyroidism (according to clinical interview) * Heartache due to insufficient blood circulation (unstable angina pectoris) or heart muscle infarct (myocardia infarct) during the last six months (according to clinical interview) * Increased intraocular pressure (glaucoma) and perforating eye injury (according to clinical interview) * Interventions in the area of the upper respiratory passages (according to clinical interview)

Study locations

Universitätsklinikum Tübingen - Klinik für Psychiatrie und Psychotherapie, Tübingen, Baden-Würtemberg 72070 Germany
Universitätsklinikum Jena - Klinik für Psychiatrie und Psychotherapie, Jena, Thuringia 07743 Germany

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.