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.
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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
Dosing
Integration
Study Arms & Interventions
Ketamine 35 mg/70 kg + lithium
active comparatorLithium 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
- Compoundvia Oral• daily
Lithium titrated to serum level ≥0.4 mEq/L; started 2 weeks pre-ketamine and continued during acute phase.
- Ketamine0.5 mg/kgvia 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 35 mg/70 kg + placebo (matched to lithium)
inactiveMatching 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
- Placebovia Oral• daily
Matching placebo tablets started 2 weeks pre-ketamine and continued during acute phase.
- Ketamine0.5 mg/kgvia 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
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 Protocol, Arms & Participants
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Study Details
- StatusWithdrawn
- PhasePhase II
- Typeinterventional
- DesignRandomizedtriple Blind0
- TimelineStart: 2017-11-30End: 2018-12-01
- Compounds
- Topic
Study Team
Sponsors & Collaborators
Investigators
- WBWilliam Bobo
Locations
Recent activity
- WithdrawnEffect of Lithium Versus Placebo in Adults With Treatment-Resistant Depression Who Are Receiving Ketamine (NCT03290963, ketamine)
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