Background
Ketamine is reported to have rapid antidepressant effects; however, there is limited
understanding of the time-course of ketamine effects beyond a single infusion. A previous
report including 10 participants with treatment-resistant major depression (TRD) found
that six ketamine infusions resulted in a sustained antidepressant effect. In the
current report, we examined the pattern and durability of antidepressant effects of
repeated ketamine infusions in a larger sample, inclusive of the original.
Methods
Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up
to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly
over a 12-day period. Participants meeting response criteria were monitored for relapse
for up to 83 days from the last infusion.
Results
The overall response rate at study end was 70.8%. There was a large mean decrease
in Montgomery–Åsberg Depression Rating Scale score at 2 hours after the first ketamine
infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion
period. Response at study end was strongly predicted by response at 4 hours (94% sensitive,
71% specific). Among responders, median time to relapse after the last ketamine infusion
was 18 days.
Conclusions
Ketamine was associated with a rapid antidepressant effect in TRD that was predictive
of a sustained effect. Future controlled studies will be required to identify strategies
to maintain an antidepressant response among patients who benefit from a course of
ketamine.
Key Words
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References
- Grand challenges in global mental health.Nature. 2011; 475: 27-30
- Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report.Am J Psychiatry. 2006; 163: 1905-1917
- Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized study.Am J Psychiatry. 2011; 168: 689-701
- Antidepressant effects of ketamine in depressed patients.Biol Psychiatry. 2000; 47: 351-354
- A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.Arch Gen Psychiatry. 2006; 63: 856-864
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: A pilot randomized, placebo-controlled continuation trial.Int J Neuropsychopharmacol. 2010; 13: 71-82
- Ketamine as a novel antidepressant: From synapse to behavior.Clin Pharmacol Ther. 2011; 91: 303-309
- Treatment-resistant depression: Recent developments and future directions.Depress Anxiety. 2008; 25: 989-992
- Therapeutic options for treatment-resistant depression.CNS Drugs. 2010; 24: 131-161
- Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder.J Clin Psychiatry. 2010; 71: 1605-1611
- Replication of ketamine's antidepressant efficacy in bipolar depression: A randomized controlled add-on trial.Biol Psychiatry. 2012; 71: 939-946
- Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: Results from a 4-week, double-blind, placebo-controlled study.Neuropsychopharmacology. 2012; 37: 1526-1533
- Neurobiology of emotion perception II: Implications for major psychiatric disorders.Biol Psychiatry. 2003; 54: 515-528
- Cracking the moody brain: Lifting the mood with ketamine.Nat Med. 2010; 16: 1384-1385
- Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression.Biol Psychiatry. 2010; 67: 139-145
- Structured Clinical Interview for DSM-IV Axis Disorders (SCID).New York State Psychiatric Institute, Biometrics Research, New York1995
- The definition and meaning of treatment-resistant depression.J Clin Psychiatry. 2001; 62: 10-17
- The Inventory of Depressive Symptomatology (IDS): Psychometric properties.Psychol Med. 1996; 26: 477-486
- A new depression scale designed to be sensitive to change.Br J Psychiatry. 1979; 134: 382-389
- Basic dimensions of change in the symptomatology of chronic schizophrenics.J Abnorm Soc Psychol. 1961; 63: 597-602
- Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS).J Trauma Stress. 1998; 11: 125-136
- A rating scale for mania: Reliability, validity and sensitivity.Br J Psychiatry. 1978; 133: 429-435
- SAFTEE: A technique for the systematic assessment of side effects in clinical trials.Psychopharmacol Bull. 1986; 22: 343-381
- Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression.Biol Psychiatry. 2009; 66: 522-526
- A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department.Int J Neuropsychopharmacol. 2011; 14: 1127-1131
- Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice.Am J Psychiatry. 2006; 163: 28-40
- Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression.J Clin Psychiatry. 2003; 64: 413-420
- Does early improvement triggered by antidepressants predict response/remission?.J Affect Disord. 2009; 115: 439-449
- mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists.Science. 2010; 329: 959-964
- NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses.Nature. 2011; 475: 91-95
- Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice.Mol Psychiatry. 2011; 16: 1068-1070
- Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study.Pain. 2009; 147: 107-115
- Ketamine: from medicine to misuse.CNS Drugs. 2006; 20: 199-218
- Psychiatric safety of ketamine in psychopharmacology research.Psychopharmacology (Berl). 2007; 192: 253-260
- Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs.Science. 1989; 244: 1360-1362
- NMDA antagonist neurotoxicity: mechanism and prevention.Science. 1991; 254: 1515-1518
- Frontal white matter abnormalities following chronic ketamine use: A diffusion tensor imaging study.Brain. 2010; 133: 2115-2122
- Reduced dorsal prefrontal gray matter after chronic ketamine use.Biol Psychiatry. 2011; 69: 42-48
Article Info
Publication History
Published online: July 30, 2012
Accepted:
June 20,
2012
Received in revised form:
June 13,
2012
Received:
May 3,
2012
Identification
Copyright
© 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
