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Acta Psychiatr Scand. 2016 Jul;134(1):48-56. doi: 10.1111/acps.12572. Epub 2016 Mar 30.

Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression.

Author information

1
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
2
Black Dog Institute, Randwick, NSW, Australia.
3
Wesley Hospital, Kogarah, NSW, Australia.
4
St George Hospital, Kogarah, NSW, Australia.
5
Royal North Shore Hospital, St Leonards, NSW, Australia.
6
University of New South Wales, Randwick, NSW, Australia.
7
University of Adelaide, Adelaide, SA, Australia.
8
Royal Adelaide Hospital, Adelaide, SA, Australia.
9
Macquarie Hospital, Sydney, NSW, Australia.
10
Schizophrenia Research Institute, Randwick, NSW, Australia.
11
Neuroscience Research Australia, Randwick, NSW, Australia.
12
Psychological Medicine, University of Otago, Dunedin, New Zealand.

Abstract

OBJECTIVE:

This pilot study assessed the feasibility, efficacy and safety of an individual dose-titration approach, and of the intravenous (IV), intramuscular (IM) and subcutaneous (SC) routes for treating depression with ketamine.

METHOD:

Fifteen treatment-refractory depressed participants received ketamine or midazolam (control treatment) in a multiple crossover, double-blind study. Ketamine was administered by IV (n = 4), IM (n = 5) or SC (n = 6) injection. Dose titration commenced at 0.1 mg/kg, increasing by 0.1 mg/kg up to 0.5 mg/kg, given in separate treatment sessions separated by ≥1 week, with one placebo control treatment randomly inserted. Mood, psychotomimetic and hemodynamic effects were assessed and plasma ketamine concentrations assayed.

RESULTS:

Twelve participants achieved response and remission criteria, achieved at doses as low as 0.1 mg/kg. All three routes of administration resulted in comparable antidepressant effects. Fewest adverse effects were noted with the SC route. Antidepressant response, adverse effects and ketamine concentrations were dose-related.

CONCLUSION:

Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose-titration approach is a practical method for optimizing the efficacy - side-effects trade-off on an individual patient basis. This pilot study provides preliminary evidence for SC injection as a practical, feasible and efficacious treatment approach.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01441505.

KEYWORDS:

dose titration; intramuscular; intranasal; intravenous; ketamine

PMID:
27028832
DOI:
10.1111/acps.12572
[Indexed for MEDLINE]

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