Clinical TrialBipolar DisorderKetamineCompleted

NMDA Antagonists in Bipolar Depression

Single-group treatment study (n=8) testing IV ketamine 0.5 mg/kg followed by an 8-week oral D-cycloserine maintenance course in patients with bipolar depression.

Target Enrollment
8 participants
Study Type
Phase IV interventional
Design
Non-randomized

Detailed Description

Open single-group treatment design in patients with bipolar I or II depression: standard-of-care medication management, ketamine infusion (0.5 mg/kg IV over 40 minutes) for symptomatic subjects, and an 8-week oral D-cycloserine maintenance course for ketamine responders.

Primary aims are feasibility and safety of D-cycloserine as a maintenance strategy after ketamine; outcomes include depressive symptom change (HDRS), safety/tolerability, and magnetic resonance spectroscopy (MRS) measures.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine + DCS

experimental

Single-group, standard-of-care followed by ketamine infusion (0.5 mg/kg IV) for responders, then 8-week oral D-cycloserine maintenance.

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose

    Ketamine hydrochloride 0.5 mg/kg infused over 40 minutes; non-responders do not proceed to DCS.

  • Compound
    via Oral• maintenance

    Standard of care: quetiapine, olanzapine-fluoxetine, or lurasidone per label; dosing titrated per clinician judgement.

  • Compound
    via Oral• daily

    D-cycloserine escalation: 250 mg ×3 days → 500 mg/day ×1 week → 750 mg/day ×1 week → 1000 mg/day for remainder (8-week course)

Participants

Ages
18 – 60
Sexes
Male & Female

Inclusion Criteria

  • Male and female patients with DSM-IV diagnosis of bipolar disorder I or II, current major depressive episode without psychotic features, 18–60 years
  • Insufficient therapeutic response during the current episode
  • Medically stable for study participation
  • Judged clinically not to be at significant suicide or violence risk
  • Off all psychotropic and other drugs likely to interact with glutamate for at least 14 days before starting the study (exception: chloral hydrate or short-acting benzodiazepines up to 72 hours prior to each MRI scan)
  • Off antipsychotics for 1 month and off fluoxetine for 6 weeks prior to the study
  • Likely to be able to tolerate a medication washout; only subjects who have failed their current medication regimen will be washed off medications.

Exclusion Criteria

  • History of chronic psychosis or drug-induced psychosis of any kind
  • Current DSM-IV diagnosis of drug abuse/dependence in the last six months; negative drug screen required at baseline
  • Women who are pregnant, lactating, or not surgically sterile or not using appropriate birth control; negative urine pregnancy test required for women of child-bearing potential
  • Taking any medication contraindicated with ketamine or DCS (e.g., ethionamide, isoniazid)
  • History of seizures, renal insufficiency, or congestive heart failure
  • History of clinically significant violence
  • History of ketamine abuse/dependence or prior clinically significant adverse reaction to ketamine
  • Current alcohol abuse or dependence
  • Untreated hypertension
  • Clinically abnormal liver function tests, thyroid or renal function, or anemia
  • Metal implants, pacemaker, or other paramagnetic objects that may present a risk or interfere with MR scan
  • Medicinal patches unless removed prior to MR scan

Study Details

  • Status
    Completed
  • Phase
    Phase IV
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment8 participants
  • Timeline
    Start: 2013-01-03
    End: 2016-01-03
  • Compound
    Ketamine
  • Topic
    Bipolar Disorder

Locations

New York State Psychiatric Institute — New York, New York, United States

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