Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression.
BACKGROUND
A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose.


METHODS
On day 1, patients received a 40-min IV infusion of ketamine (.5 mg/kg) in an inpatient setting with continuous vital-sign monitoring. Psychotomimetic effects and adverse events were recorded repeatedly. The primary efficacy measure was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) score. If patients showed a > or =50% reduction in MADRS scores on day 2, they received five additional infusions on an outpatient basis (days 3, 5, 8, 10, and 12). Follow-up visits were conducted twice-weekly for > or =4 weeks or until relapse.


RESULTS
Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild. The response criterion was met by nine patients after the first infusion as well as after the sixth infusion. The mean (SD) reduction in MADRS scores after the sixth infusion was 85% (12%). Postketamine, eight of nine patients relapsed, on average, 19 days after the sixth infusion (range 6 days-45 days). One patient remained antidepressant-free with minimal depressive symptoms for >3 months.


CONCLUSIONS
These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.
aan het Rot
Marije
M
Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York. m.aan.het.rot@rug.nl
Collins
Katherine A
KA
Murrough
James W
JW
Perez
Andrew M
AM
Reich
David L
DL
Charney
Dennis S
DS
Mathew
Sanjay J
SJ
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D018570:Risk Assessment; D013997:Time Factors
D000700:Analgesics; D007649:Ketamine