Naloxone in the Prevention of the Adverse Cognitive Effects of ECT A Within-Subject, Placebo Controlled Study

Abstract

Electroconvulsive therapy (ECT) is a highly effective treatment for major depression, but is also associated with characteristic cognitive side effects. Several reports document that endogenous opioids and their receptors are activated by electroconvulsive shock (ECS) and that naloxone in doses sufficient to block endogenous opioid receptors may reverse ECS-induced retrograde amnesia. This placebo-controlled, randomized, within-patient study was conducted to examine the potential of naloxone, given in doses sufficient to block opioid receptors (high dose)Electroconvulsive therapy (ECT) is a highly effective treatment for major depression and a variety of other disorders . However, the cognitive side effects of ECT are the major factor limiting its use. The cognitive consequences of ECT involve a period of postictal disorientation immediately following the induced seizure, as well as a pattern of more sustained neuropsychological deficits, principally anterograde and retrograde amnesia .There is substantial evidence that electroconvulsive shock (ECS) in experimental animals alters the concentrations of endogenous opioid peptides and the density of their receptors (Holaday et al. 1986). Opioids produce effects through at least three different receptors, , ␦ , and (Mansour et al. 1988; Quirion 1988). The receptors and ␦ have been extensively studied, and agonists at these receptors generally interfere with learning and memory, resulting in both anterograde and retrograde amnesia. The role of receptors in learning and memory is more complex. While agonists may impair memory in a dose-dependent fashion (Colombo et al., 1992), From they may also ameliorate memory deficits due to disruption of cholinergic transmission (Hiramatsu et al. 1996).Repeated ECS stimulates the release of proenkephalin and proopiomelanocortin ( ␤ -endorphin) (Tortella et al. 1989) and results in increased abundance of mRNA for preproenkepohalin in the hypothalmus and hippocampus (Yoshikawa et al. 1985;Xie et al. 1989;Simmons and Chavkin 1996). In the perforant pathway, projecting from entorhinal cortex to the hippocampal dentate gyrus, repeated ECS results in increased enkephalin immunostaining. In contrast, the release of dynorphin appears to be more complex. While increased dynorphin immunostaining has been found in limbic and basal ganglia structures, chronic ECS results in decreased levels in the mossy fiber axons of the dentate granule cells (Kanamatsu et al. 1986;Lasön et al. 1992). Overall, it appears that repeated ECS results in widespread increased synthesis and release in the proenkephalin system, and large decreases in the prodynorphin system in the hippocampus. Increased peptide synthesis and release may account for some findings of a sustained decreased density of and ␦ receptors following chronic ECS (Nakata et al. 1985;Crain et al. 1987). In humans, ECT has been found to result acutely in large increases in plasma ␤ -endorphin immunoreactivity (Alexopoulos et al. 1983;Weizman et al. 1987;Young et al. 1991).In a number of models...

The Effect of Naltrexone on Memory Deficit Followed by Electroconvulsive Therapy: A Randomized, Double-Blind, Placebo-Controlled Trial

“…2017; 19 (9):e59814. 5 tained results showed that high dose of naloxone is fruitless in retrograde memory tests, even leaving a negative trace in "shape stimuli" test evaluation (17).…”

“…Ability of naloxone as an opioid receptor antagonist has been discussed in animal studies (23,24). Also, human studies based on the ability of naloxone have been leading to paradoxical results (17,25).…”

“…Naltrexone and other toll like receptor 4 (TLR4) antagonists could cause an exquisite therapeutic method to reduce the main problems of memory or executive cognitive function disorder after cardiac arrest/cardiopulmonary resuscitation (14). In one of the few studies on humans, naloxone infusion compared with placebo had a positive impact on cognitive impairments of ECT (17). The evidences provide a foundation for the hypothesis that by manipulation of opioid systems, memory dysfunction after ECT could be reduced in affected patients.…”

Further improving the cognitive effect profile of electroconvulsive therapy (ECT): The case for studying carbamylated erythropoietin

“…Like piracetam, studies demonstrated inconsistent results. One study failed to show a significant effect [13], while in another later study, naloxone improved anterograde amnesia after ECT, but seemed to worsen retrograde amnesia [14].…”

Kognitive Störungen und Elektrokrampftherapie

“…Mit der Anwendung des NMDA-Antagonisten Ketamin als Anästhetikum anstatt der üblichen kurzwirksamen Barbiturate könnte man selektiv und damit protektiv in diesen Mechanismus eingreifen [61]. Klinisch geprüft wurde die Anwendung von Naltrexon [62]. Verabreichte man Naltrexon in ausreichender Dosierung zur Blockierung der Opioidrezeptoren, beobachtete man klinisch eine deutliche Besserung der anterograden Amnesie sowie der Aufmerksamkeitsleistung im direkten Vergleich zu Placebo und niedrigen Dosen von Naltrexon.…”