Abstract
Bruce Boman, Rozelle Hospital, Sydney, Australia:
Three drugs are available in Australia for the treatment of mild to moderate Alzheimer's disease: donepezil, rivastigmine and galantamine. All act by increasing brain acetylcholine levels via their blockade of acetylcholinesterase. I would like to raise three concerns about their concurrent use with electroconvulsive therapy (ECT).
First, there is the synergistic enhancement of neuromuscular blockade with suxamethonium, a muscle relaxant which binds to the postsynaptic muscle receptor causing initial depolarization followed by blockade. It is metabolized by pseudocholinesterase. Hence any drugs that reduce pseudocholinesterase activity will enhance neuromuscular blockade leading to prolonged apnoea and paralysis when used with suxamethonium. There are reports of both prolonged apnoea and death with the concurrent use of suxamethonium and ecothiopate eye drops, a cholinesterase inhibitor used for glaucoma [1]. Of the cholinesterase inhibitors used for Alzheimer's disease, tacrine does reduce pseudocholinesterase activity [1] and it is likely donepezil, rivastigmine and galantamine would have a similar effect [2, 3]. Donepezil would be particularly problematic because of its 70 hour half-life and washout period of 14 days leading to delay before ECT could be commenced without the risk of prolonged apnoea.
Second, there is the synergistic potential for the cholinesterase inhibitors, ECT and suxamethonium to induce significant bradycardia, cardiac arrhythmias and asystole. Administration of ECT is associated with two powerful vagal parasympathetic surges, the first with the passage of the electrical current, the second immediately following ictal activity, and both sinus bradycardia and periods of asystole lasting several seconds are not uncommon [4]. Suxamethonium also causes bradycardia and asystole and caution is recommended in using it concurrently with drugs of similar effect [1]. Thus, adding a cholinesterase inhibitor that has the potential for further increasing vagal parasympathetic activity may carry the risk of causing serious cardiac events.
Third, because cholinomimetics are believed to have the potential to cause generalized convulsions [2, 3], there is the possibility of a reduced threshold when used with ECT, increasing the risk of prolonged seizures and status epilepticus.
While a MEDLINE search and a review conducted by the three relevant pharmaceutical companies (Novartis, Pfizer and Janssen-Cilag) failed to find any reports of adverse incidents involving concurrent use of ECT and cholinesterase inhibitors, it would seem prudent to factor in what are potential dangers when considering the risk benefit analysis of administering ECT to a patient on a cholinesterase inhibitor, and to ensure the patient is fully aware of such risks.