Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboKetamineRecruiting

Pharmacologic Treatment Augmentation in Chronic Depression (Ket+CBASP)

Randomised, quadruple-blind, Phase II trial (n=60) comparing ketamine (0.5 mg/kg IV, 6 infusions over 3 weeks) plus CBASP or TAU versus placebo plus CBASP in patients with stage-2 treatment-resistant chronic depression.

Target Enrollment
60 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This parallel, randomised study enrols adults 18–64 with chronic, treatment‑resistant depression (stage 2) and randomises them to Ketamine+CBASP, Ketamine+TAU, or Placebo+CBASP. Psychotherapy (CBASP or TAU) runs alongside drug/placebo administration.

Drug treatment comprises 0.5 mg/kg ketamine infusions administered intravenously twice weekly for three weeks (six 40‑minute infusions). Placebo is isotonic saline administered with the same schedule. Outcomes include clinical scales, blood biomarkers, and fMRI at baseline, during, and at follow‑up.

Screening includes clinical interview, physical exam, ECG, urine drug screen and blood tests including pregnancy testing. Follow-up therapy is arranged after study completion; final data collection occurs three months after treatment end.

Study Protocol

Preparation

sessions

Dosing

6 sessions
40 min each

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Ketamine+TAU

experimental

Ketamine infusions combined with treatment-as-usual psychotherapeutic programme.

Interventions

  • Ketamine0.5 mg/kg
    via IV• twice weekly for 3 weeks• 6 doses total

    Infusions over ~40 minutes (subanaesthetic).

  • Compound
    via Other• concurrent psychotherapy (TAU)

    Standard ward programme: group and individual sessions, CBT, sociotherapy, occupational and physiotherapy.

Placebo+CBASP

inactive

Saline infusions with CBASP psychotherapy.

Interventions

  • Placebo
    via IV• twice weekly for 3 weeks• 6 doses total

    Isotonic saline infusion over ~40 minutes.

  • Compound
    via Other• CBASP weekly for 12 weeks plus two individual sessions/week

    CBASP group (50 min/week) and individual sessions (50 min + 25 min/week).

Ketamine+CBASP

experimental

Ketamine infusions combined with CBASP psychotherapy.

Interventions

  • Ketamine0.5 mg/kg
    via IV• twice weekly for 3 weeks• 6 doses total

    Infusions over ~40 minutes (subanaesthetic).

  • Compound
    via Other• CBASP weekly for 12 weeks plus two individual sessions/week

    CBASP group (50 min/week) and individual sessions (50 min + 25 min/week).

Participants

Ages
18 – 64
Sexes
Male & Female

Inclusion Criteria

  • 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) or acute depressive episode lasting two or more years.
  • Treatment resistance stage 2 according to Thase and Rush (1997): at least two adequate antidepressant trials from different classes without sufficient response.
  • At least 12 sessions of psychotherapeutic treatment (psychoanalysis, depth psychology-based psychotherapy or cognitive behaviour therapy) without significant and sustainable improvement.
  • Able to understand and voluntarily sign informed consent and adhere to study schedule.
  • Females of childbearing potential must agree to use two reliable forms of contraception or abstain from heterosexual contact from study start until 28 days after last infusion.
  • Males must agree to use a latex condom with FCBP from first infusion until 65 days after last infusion; agree not to donate semen during that period.
  • Agreement to refrain from donating blood from first infusion until 28 days after last infusion and not to share medication.

Exclusion Criteria

  • Exclusion Criteria:
  • Acute substance misuse as primary diagnosis (assessed by SCID).
  • Neurologic disorders: stroke, cerebral ischemia, tumour, cerebral infection, autoimmune disease.
  • Disorders with increased intracranial pressure (e.g., due to head injury).
  • Circulatory disturbances in the brain.
  • Pregnant or lactating females.
  • Participation in any clinical study or having taken investigational therapy that would interfere with primary end point.
  • Epilepsy.
  • History of hypersensitivity to ketamine or related compounds or excipients.
  • Prior treatment with ketamine hydrochloride (Ketamin Inresa 2 ml) and/or prior CBASP treatment.
  • Uncontrolled or insufficiently treated hypertension (excluded if repeated measures >150/100 mmHg or lifetime diagnosis of hypertension reported).
  • Uncontrolled hyperthyroidism.
  • Recent unstable angina or myocardial infarct within last six months.
  • Increased intraocular pressure (glaucoma) or perforating eye injury.
  • Recent interventions in upper respiratory passages.

Study Details

Locations

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

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