RESUMEN
Background: N-acetyl cysteine (NAC) appears promising as a treatment in patients with substance use disorder (SUD) as it helps rebalance glutamate levels in the central nervous system (CNS). Basal concentrations of glutamate are indeed reduced in SUD patients but increased during craving. Materials and Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether NAC reduce craving rating as compared to a placebo in SUD patients. Secondary outcomes were withdrawal symptoms (WS), side effects (SE) and drop-outs. Estimates are presented as standardized mean differences (SMD) or risk ratio (RR) with 95% confidence interval (CI). Results: Eleven RCTs were included. NAC reduced craving rating (SMD -0.61 (-1.17, -0.06), p = 0.03, I2 = 85%), with no differences in the subgroup analysis according to the drug addiction (alcohol, cocaine, poly-drugs, amphetamine, nicotine) (p = 0.98). Among the secondary outcomes, for WS data showed no significant difference between groups (SMD -0.18 (-0.43, 0.08), p = 0.17); for SE no substantial difference was observed between the two treatment groups (RR = 1.06 (0.89-1.27), p = 0.52, I2 = 0%); for dropouts the results are in favor of the placebo but no statistically significant (RR 1.17 (0.85, 1.61), p = 0.34; I2 = 0%). Conclusion: NAC seem to reduce craving rating in SUD patients, but evidence is weak. More studies are needed to confirm this finding.
RESUMEN
Melatonin modulates the circadian rhythm and has been studied as a preventive measure against the development of delirium in hospitalized patients. Such an effect may be more evident in patients admitted to the ICU, but findings from the literature are conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether melatonin or ramelteon (melatonin agonist) reduce delirium incidence as compared to a placebo in ICU patients. Secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV) and mortality. Estimates are presented as risk ratio (RR) or mean differences (MD) with 95% confidence interval (CI). Nine RCTs were included, six of them reporting delirium incidence. Neither melatonin nor ramelteon reduced delirium incidence (RR 0.76 (0.54, 1.07), p = 0.12; I2 = 64%), although a sensitivity analysis conducted adding other four studies showed a reduction in the risk of delirium (RR = 0.67 (95%CI 0.48, 0.92), p = 0.01; I2 = 67). Among the secondary outcomes, we found a trend towards a reduction in the duration of MV (MD -2.80 (-6.06, 0.47), p = 0.09; I2 = 94%) but no differences in ICU-LOS (MD -0.26 (95%CI -0.89, 0.37), p = 0.42; I2 = 75%) and mortality (RR = 0.85 (95%CI 0.63, 1.15), p = 0.30; I2 = 0%). Melatonin and ramelteon do not seem to reduce delirium incidence in ICU patients but evidence is weak. More studies are needed to confirm this finding.