TY - JOUR
T1 - NMDA receptor antagonists and pain relief
T2 - A meta-analysis of experimental trials
AU - Thompson, Trevor
AU - Whiter, Fiona
AU - Gallop, Katy
AU - Veronese, Nicola
AU - Solmi, Marco
AU - Newton, Paul
AU - Stubbs, Brendon
PY - 2019/4/2
Y1 - 2019/4/2
N2 - OBJECTIVE: We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of NMDA receptor (NMDAR) antagonists. METHODS: Six major databases were systematically searched (to March 2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis. RESULTS: Searches identified 70 eligible trials (n = 1,069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in hyperalgesic area (standardized mean difference 0.54, 95% confidence interval [CI] 0.34, 0.74, p < 0.001) and a 1.2-point decrease (95% CI 0.88, 1.44, p < 0.001) in pain ratings from 4.6 to 3.4 on a 0-10 scale (a 26% reduction). Similar analgesia was observed for acute and hyperalgesic models and was constant across the dosing range (0.03-1.00 mg/kg). Moderate to high variability in effect size was observed and mild side effects (e.g., sedation, sensory disturbance) were common. No effects of dextromethorphan were found. CONCLUSIONS: Findings provide robust evidence for analgesic and antihyperalgesic effects of ketamine, supporting its utility for acute and chronic pain management. However, pain relief was modest, suggesting ketamine may potentially be most useful when opioids are contraindicated, rapid analgesia is required, or for pain resistant to conventional medication.
AB - OBJECTIVE: We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of NMDA receptor (NMDAR) antagonists. METHODS: Six major databases were systematically searched (to March 2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis. RESULTS: Searches identified 70 eligible trials (n = 1,069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in hyperalgesic area (standardized mean difference 0.54, 95% confidence interval [CI] 0.34, 0.74, p < 0.001) and a 1.2-point decrease (95% CI 0.88, 1.44, p < 0.001) in pain ratings from 4.6 to 3.4 on a 0-10 scale (a 26% reduction). Similar analgesia was observed for acute and hyperalgesic models and was constant across the dosing range (0.03-1.00 mg/kg). Moderate to high variability in effect size was observed and mild side effects (e.g., sedation, sensory disturbance) were common. No effects of dextromethorphan were found. CONCLUSIONS: Findings provide robust evidence for analgesic and antihyperalgesic effects of ketamine, supporting its utility for acute and chronic pain management. However, pain relief was modest, suggesting ketamine may potentially be most useful when opioids are contraindicated, rapid analgesia is required, or for pain resistant to conventional medication.
UR - http://www.scopus.com/inward/record.url?scp=85064198749&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000007238
DO - 10.1212/WNL.0000000000007238
M3 - Article
C2 - 30842296
AN - SCOPUS:85064198749
SN - 0028-3878
VL - 92
SP - e1652-e1662
JO - Neurology
JF - Neurology
IS - 14
ER -