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|Title:||Neurocognitive and behavioural performance of healthy volunteers receiving an increasing analgesic-range infusion of ketamine.|
|Authors:||Hayley, Amie;Green, Maja;Downey, Luke A;Keane, Michael;Kostakis, Panagiota;Shehabi, Yahya|
|Affiliation:||Centre for Human Psychopharmacology, Faculty of Health, Arts and Design, Swinburne University of Technology, Hawthorn, Victoria, 3122, Australia|
Program of Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
Department of Oncology, Monash Health Translation Precinct, Monash University, Clayton, Australia
Institute for Breathing and Sleep, Austin Health, Heidelberg, Victoria, Australia
Forensic Science South Australia (FSSA), Adelaide, South Australia, Australia
|Citation:||Psychopharmacology 2018; online first: 23 February|
|Abstract:||The acute and delayed effect of analgesic-range doses of ketamine on neurocognitive and behavioural outcomes is understudied. Using a non-controlled open-labelled design, three (1-h duration) increasing intravenous (IV) ketamine infusions comprising (i) 30 mg bolus of ketamine + 8 mg/h IV infusion, (ii) 12 mg/h IV infusion and (iii) 20 mg/h infusion were administered to 20 participants (15 male, 5 female, mean age = 30.8 years). Whole-blood ketamine and norketamine concentrations were determined at each treatment step and post-infusion. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess reaction/movement time (RTI, Simple and 5-Choice), visuospatial working memory (SWM), spatial planning (SOC) and subjective effects (visual analogue scale; VAS) during treatment and at post-treatment. Significant main effects were reported for time (dose) on CANTAB RTI 5-Choice reaction (F(4,18) = 3.41, p = 0.029) and movement time (F(4,18) = 4.42, p = 0.011), SWM (F(4,18) = 4.19, p = 0.014) and SOC (F(4,18) = 4.13, p = 0.015), but not RTI Simple reaction or movement time. Post hoc analyses revealed dose-dependent effects for both RTI 5-Choice reaction and movement time (all p < 0.05). Post-treatment performance on all neurocognitive and behavioural tasks returned to baseline levels. Regression analyses revealed a weak positive linear association between SWM 'strategy' score (R2 = 0.103, p < 0.001), all performance-based CANTAB VAS items (R2range 0.005-0.137, all p < 0.05) and ketamine blood concentrations. The open-label, non-controlled trial design somewhat precludes the ability to adequately account for random treatment effects. Notwithstanding, these results suggest that analgesic doses of ketamine produce acute, selective, dose-dependent deficits in higher-order neurocognitive and behavioural domains.|
|Appears in Collections:||Journal articles|
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