Pharmacologic Treatment Augmentation in Chronic Depression

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)