Clinical TrialTreatment-Resistant Depression (TRD)KetamineKetaminePlaceboCompleted

Ketamine Plus Lithium in Treatment-Resistant Depression

Randomized, double-blind, placebo-controlled Phase II study (n=34) testing repeated ketamine infusions over 1 week with nightly lithium (600–1200 mg) versus placebo pills in treatment-resistant major depressive disorder to assess efficacy and relapse prevention.

Target Enrollment
34 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Randomized, double-blind, parallel-group Phase II trial in adults (21–65) with treatment-resistant major depressive disorder comparing ketamine infusions plus lithium versus ketamine plus placebo; target enrollment 34.

Primary aim is to test whether adjunctive lithium sustains ketamine's rapid antidepressant effects; secondary aims include safety, tolerability, and effects on brain function.

Study Arms & Interventions

Ketamine + Lithium

experimental

Ketamine infusions combined with nightly lithium (600–1200 mg).

Interventions

  • Ketamine
    via IV• multiple infusions

    Repeated ketamine infusions over 1 week per protocol.

  • Compound
    via Oral

    Lithium carbonate 600–1200 mg nightly for duration of study.

Ketamine + Placebo

inactive

Ketamine infusions with nightly placebo pills.

Interventions

  • Ketamine
    via IV• multiple infusions

    Repeated ketamine infusions over 1 week per protocol.

  • Placebo
    via Oral

    Placebo pills nightly for duration of study.

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion Criteria

  • Male or female patients, 21-65 years of age;
  • Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum B-HCG at screening and at pre-infusion;
  • Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
  • Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
  • Participants have not responded to two or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
  • Current Major Depressive Episode of at least moderate severity, defined as a QIDS-SR score >= 14 and a CGI-S score of >= 4; Current major depressive episode is of at least 4 weeks duration;
  • Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
  • Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

Exclusion Criteria

  • Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder;
  • Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
  • Current diagnosis of OCD or eating disorder (bulimia nervosa or anorexia nervosa);
  • Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
  • Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
  • Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
  • Women who are either pregnant or nursing;
  • Serious, unstable medical illnesses including hepatic, renal impairment, gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
  • Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
  • Patients who have a positive urine toxicology for illicit substances at screening and within 24 hours of the infusion;
  • Patients with one or more seizures without a clear and resolved etiology;
  • Treatment with an irreversible MAOI within 2 weeks prior to randomization or fluoxetine within 4 weeks prior to randomization;
  • Treatment with other antidepressants within one week of randomization;
  • Previous recreational use of PCP or ketamine;
  • Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination;
  • A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
  • Renal impairment, as reflected by a BUN > 20 mg/dL and/or creatinin clearance of >1.3 mg/dL;
  • Thyroid impairment, as reflected by a TSH > 4.2 mU/L;
  • Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac disease;
  • Any anticipated change in medications that could affect fluid or salt balance, including the following antihypertensive agents: ACE inhibitor, loop diuretics, calcium channel blockers, thiazide diuretics, angiotensin II receptor blockers.

Study Details

Locations

Icahn School of Medicine at Mount Sinai — New York, New York, United States

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