Prolongation of ECT-induced seizures with theophylline.

Abstract

To the Editor: Electroconvulsive therapy (ECT) is well established as a safe and effective treatment for major depression in older people.1 An important technical consideration in the use of ECT concerns the increase in seizure threshold, and consequent increase in required electrical charge to obtain an adequate seizure, during a series of treatments.2 This, coupled with generally higher seizure thresholds among older people,1 may ultimately result in inadequate seizure duration, even at maximum settings, on currently available machines. One way of addressing this problem is by treatment with intravenous caffeine sodium benzoate immediately before induction of anesthesia.3 Although there are at least two reports of adverse cardiovascular effects of IV caffeine,4, 5 it is generally well tolerated. Alternatively, Swartz and Lewis have reported the efficacy of a more readily available methylxanthine derivative, theophylline, in lowering seizure threshold for ECT.6 We recently treated a patient for delusional depression with ECT; sustained-release theophylline, given at bedtime before treatments, proved effective in maintaining seizure duration. A 65-year-old man with an 18-month history of major depression with mood-congruent psychotic features was readmitted because of a recurrence of symptoms. He had responded twice previously to courses of ECT, but he had relapsed in spite of prophylaxis with either fluoxetine or sertraline. There was no history consistent with mania, nor was there any evidence of dementia. Medical history was remarkable only for glaucoma. Medications, in addition to sertraline, included acetazolamide 250 mg QID and a variety of eye drops. In the hospital, the patient failed to respond to a trial of nortriptyline or augmentation with methylphenidate. As a result of his delusions, he required nasogastric tube feedings to maintain adequate nutrition and hydration. Ultimately, a course of bilateral brief-pulse ECT was begun, using a Thymatron DGx machine. The patient's first seizure lasted 68 seconds, but the next two lasted only 31 and 28 seconds, respectively. In spite of vigorous hyperventilation, minimizing methohexital dosage, increasing power to maximum settings, and decreasing pulse width to 0.5 ms, the subsequent three seizures lasted only between 25 and 30 seconds. However, the patient gradually continued to improve. Because of concern about further decreases in seizure length, 450 mg sustained-release theophylline was begun on the evenings before ECT. Additionally, acetazolamide was discontinued, and dorzolamide, a topical carbonic anhydrase inhibitor, was substituted. Seizure durations for the subsequent three treatments were between 38 and 46 seconds. Serum theophylline levels drawn on the mornings of treatment ranged between 8.2 and 9.6 mcg/mL. There was no evidence of arrhythmia or other toxicity. The patient's depressive and psychotic symptoms ultimately resolved completely, and he was discharged home on prophylactic medication. As has been reported by Swartz and Lewis, sustained-release theophylline has been effective and quite well tolerated as an adjunct to electroconvulsive therapy in patients with elevated seizure threshold.6 Methylxanthine derivatives such as caffeine and theophylline probably lower seizure threshold through blockade of adenosine receptors.7 It was felt previously that ECT was quite risky in patients taking theophylline because of the possibility of status epilepticus. This issue has been reviewed by Rasmussen and Zorumski.8 Problems have usually been associated with toxic theophylline levels, in contrast to the relativity subtheraputic levels reported here and by Swartz and Lewis. It is possible that improvement in seizure duration was at least, in part, attributable to discontinuation of acetazolamide, which has limited anticonvulsant effects.9 Nevertheless, sustained-released oral theophylline may be a safe, effective, and more readily available alternative to IV caffeine sodium benzoate in prolonging seizure duration in patients receiving ECT.