Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboKetamineWithdrawn

Effect of Lithium Versus Placebo in Adults With Treatment-Resistant Depression Who Are Receiving Ketamine

Randomised, triple-blind, parallel trial (n=0) comparing lithium versus placebo given for 2 weeks prior to three IV ketamine infusions (0.5 mg/kg over 100 minutes) in adults with treatment-resistant depression.

Target Enrollment
Not specified
Study Type
Phase II interventional
Design
Randomized, triple Blind

Detailed Description

Participants are randomised to receive lithium or matching placebo for two weeks prior to an acute course of three intravenous ketamine infusions (0.5 mg/kg each, over 100 minutes across 7 days). Lithium/placebo is continued in a double-blind fashion during the acute ketamine phase.

Questionnaires and rating scales are administered at baseline, before each infusion, at 40, 100 and 120 minutes after each infusion, and weekly for 4 weeks after the third infusion; responders (>50% reduction in score) may receive four additional once-weekly ketamine infusions.

Study Protocol

Preparation

sessions

Dosing

3 sessions
100 min each

Integration

sessions

Study Arms & Interventions

Ketamine + Lithium

active comparator

Lithium started 2 weeks before first ketamine infusion and continued during acute phase; all subjects receive three IV ketamine infusions (0.5 mg/kg over 100 min) over 7 days; responders may receive 4 additional weekly infusions.

Interventions

  • Compound
    via Oral• daily

    Lithium titrated to serum level ≥0.4 mEq/L; started 2 weeks pre-ketamine and continued during acute phase.

  • Ketamine0.5 mg/kg
    via IV• three infusions over 7 days• 3 doses total

    Each infusion 0.5 mg/kg over 100 minutes; responders receive 4 additional once-weekly infusions.

Ketamine + Placebo

inactive

Matching placebo tablets started 2 weeks before first ketamine infusion and continued during acute phase; all subjects receive three IV ketamine infusions (0.5 mg/kg over 100 min) over 7 days.

Interventions

  • Placebo
    via Oral• daily

    Matching placebo tablets started 2 weeks pre-ketamine and continued during acute phase.

  • Ketamine0.5 mg/kg
    via IV• three infusions over 7 days• 3 doses total

    Each infusion 0.5 mg/kg over 100 minutes; responders receive 4 additional once-weekly infusions.

Participants

Ages
18 – 62
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Ability to provide informed consent;
  • Current psychiatric inpatient (voluntary only) or outpatient treatment;
  • Meets DSM-5 diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder;
  • PHQ-9 total score > 15 at screening and at baseline (just prior to first acute phase ketamine infusion);
  • Treatment-resistant depression (failure of at least two previous antidepressant or mood stabilising treatments within the current depressive episode; failed treatments can include adequate pharmacotherapy for ≥8 weeks or an acute series of ≥6 ECT administrations);
  • Adequate social support (at least one individual identified to provide transportation to/from ketamine visits);
  • Ability to pass a comprehension assessment related to ketamine effects and trial objectives/criteria.

Exclusion Criteria

  • Exclusion Criteria:
  • Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms;
  • On active lithium treatment;
  • Serious risk for suicide as assessed by the evaluating study clinician (a serious suicide risk defined as: (a) inability to control suicide impulses or imminent/unacceptably high risk in investigator's judgment; or (b) recent history of suicidal behaviour: one or more suicide attempts/interrupted attempts in the 12 months before study entry; or (c) history of serious suicidal behaviour: one or more suicide attempts/interrupted attempts in the last 3 years with potential lethality judged to have possibly resulted in serious injury or death);
  • Ongoing prescription of >4 mg lorazepam equivalents daily, or morning dosing of any benzodiazepine at assessment;
  • Currently undergoing ECT, rTMS, VNS, or DBS as acute or maintenance treatment for depression;
  • Any active or unstable medical condition judged by the study psychiatrist to confer too great medical risk;
  • Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed or illicit) within the past 12 months;
  • Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine); persons with sustained remission >1 year may be eligible;
  • History of traumatic brain injury with loss of consciousness;
  • Developmental delay, intellectual disorder, or prior delirium/encephalopathy within prior 12 months;
  • Cognitive disorder (mild or major per DSM-5);
  • Prior participation in another ketamine-for-depression study within prior 6 months;
  • History of poor antidepressant response to or poor tolerability of ketamine previously administered for depression;
  • History of hypothyroidism unless stable on thyroid medication and asymptomatic for 6 months;
  • Significant unstable medical condition;
  • Hepatic insufficiency (AST or ALT ≥2.5× ULN within 1 year of consent), past liver transplant, or clinical cirrhosis;
  • History of medical conditions not recommended to be taken concurrently with lithium; current antidepressant pharmacotherapies not allowed during acute ketamine infusions;
  • Pregnancy or nursing;
  • Prisoners;
  • Involuntary psychiatric hospitalization.

Study Details

Locations

Mayo Clinic in Rochester — Rochester, Minnesota, United States

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