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Friday, April 4, 2008

7 Drugs Attenuating Cognitive Side-effects of ECT?

The new Journal of ECT is out. This number is all about side-effetc of ECT. An important issue to my opinion. One important article of this issue is Pharmacological Attenuation of Electroconvulsive Therapy-Induced Cognitive Deficits

The most important psychopharmacological agents in the attenuation of ECT-induced cognitive deficits studied up until now are:

  • Ketamine anesthesia in ECT might be neuroprotective according to a retrospective study. In this study it was reported that a significantly quicker recovery of orientation in 36 patients who were switched from methohexital to ketamine anesthesia appeared midway through the ECT course because of insufficient seizure duration with the barbiturate anesthetic drug. In another trial etomidate was compared to ketamine anesthesia across 6 ECT sessions in 10 patients. Anterograde memory function (tested simply as short-term memory for 4 words) was significantly better in the ketamine group. There is some fear that ketamine might attenuate the convulsion as well adn thus hamper therapeutic efficacy. Ketamine also has some troublesome side-effects such as hallucinations.

  • There are no clinical trials that have assessed the inflammatory hypotheses in the context of ECT. However, across a 6-month period, indomethacin (100-150 mg/d) was found to protect against cognitive decline in patients with Alzheimer disease as compared with placebo-treated patients. In animal studies there is some attenuation of cognitive side effects of ECT by cox-2 inhibitors.

  • Calcium channel blockers (antihypertensive drugs) with the exception of nifedipine,seem to consistently preserve task recall after ECS in rats. The preclinical findings of the memory-preserving effects of these drugs have not been replicated in human subjects in the context of ECT. Two placebo controlled trials were negative.

  • Three clinical trials have assessed the antiamnestic effects of cholinesterase inhibitors (ChEIs) in the context of ECT. The results of these trials suggest that the coadministration of ChEI with ECT may compensate for or correct the ECT-induced cholinergic changes, which putatively, at least, partly explain cognitive impairment with ECT.

  • Mifepristone (40 mg/kg), a glucocorticoid receptor antagonist, administered 1 hour before ECS prevented the development of retrograde amnesia (for passive avoidance learning) induced by 5 once-daily ECS. This result supports the hypothesis for the involvement of glucocorticoid mechanisms in ECT-induced amnestic deficits. There are no published data with patients treated with ECT. One placebo-controlled clinical trial is currently being conducted using a 600-mg/d dose of mifepristone during the course of ECT; no data are available as yet

  • Thyrotropin-releasing hormone (0.5 mg)showed disappointing results in 2 trials.

  • Naloxone showed in 2 trials essentially negative results. These could be due to the relatively low dose of naloxone administered and the crossover design of the two trials. It has been suggested the dose of naloxone should be between 1 to 4 mg/kg to produce demonstrable effects. However, considering the possible risk of increased retrograde amnesia with naloxone 1.6 mg/kg as shown in one of these trials, higher doses should be used with caution.

Allthough the explaining mechaniosm of action of the mentioned drugs the results on the side effects of ECT of these drugs are disappointing. It is questionable whether better research would deliver better results. Drugs or group of drugs that may reward further investigation include ketamine or other NMDA receptor antagonists, Cox-II inhibitors, mifepristone and calcium channel blockers.
Pigot, M., Andrade, C., FRANZCP, C.L. (2008). Pharmacological Attenuation of Electroconvulsive Therapy-Induced Cognitive Deficits. The Journal of ECT, 24(1), 57-67. DOI: 10.1097/YCT.0b013e3181616c14


Anonymous said...

Thanks for the interesting blog post.

As far as I know, Indomethacin is a normal NSAID and is not a selective COX-II inhibitor and inhibits both COX-1 and 2.

Dr. Shock said...

Your absolutely right, changed it in the post, thanks and regards
Dr Shock