Many patients are on medications for psychiatric and medical conditions at the time they begin electroconvulsive treatment (ECT). An understanding of the interaction of medications and ECT is essential to ensure that the use of medications does not jeopardize the efficacy and safety of this treatment.
In 1990, the American Psychiatric Association published a task force report on ECT that recommended that "all ongoing psychotropic and medical agents be reviewed as part of the pre-ECT evaluation."1 It was also suggested that psychotropic medications be discontinued, if possible, prior to ECT These pragmatic recommendations underscore the need for careful consideration of possible interactions between medications and ECT, and the importance of discontinuing medications, if possible, before the course of treatment begins.
Medications can be particularly important during the course of ECT in the following ways:
* by increasing or decreasing the seizure activity,
* by increasing the risk of post-treatment organic brain syndrome, and
* by modifying the cardiovascular response to ECT.
The clinician should approach the initiation of ECT with a knowledge of how the current medication regimen will affect these areas.
MEDICATIONS AND SEIZURE ACTIVITY
Traditionally, it has been thought that for ECT to be efficacious, the induced seizure must be of sufficient duration. Currently, attention is being given to identifying factors that affect the seizure threshold. Many psychotropic, anesthetic, and anticonvulsant medications alter the seizure threshold2 (see Figure) and may affect the efficacy of ECT. It is useful to consider the proconvulsant and anticonvulsant effects of medications.
Medications and Seizure Activity
Benzodiazepines are frequently administered to psychiatric populations. Benzodiazepines are known to potentiate neural inhibition mediated by gammaaminobutyric acid (GABA).3' pp349"350) This inhibitory effect may interfere with the efficacy of ECT by diminishing seizure activity. Pettinati et al4 studied the effectiveness of ECT in patients taking benzodiazepines during a course of unilateral ECT. They found a significant relationship between the therapeutic failure of ECT when patients were also taking benzodiazepines. Even patients who had a therapeutic response to ECT had smaller changes in their Hamilton Depression Rating scores than patients not exposed to benzodiazepines.
Sackeim2 notes that many patients experience intolerable anxiety during their course of ECT treatment. He advises that, if benzodiazepines must be used, use low-dosage short half-life agents, such as lorazepam, at least 8 to 12 hours before the next ECT treatment.
Anticonvulsant medications obviously affect seizure activity, and some patients being treated with anticonvulsant medications for seizure disorders have been treated with ECT They often cannot be tapered off these medications because of the risk of a recurrence of their seizures. These medications will need to be continued in most patients. If a patient fails to have an induced seizure during a course of ECT, the stimulus intensity of the treatment can be titrated upward.
The barbiturate agent used to anesthetize the patient for ECT can also adversely affect seizure duration. Using smaller doses of barbiturates (i.e., methohexital, 0.75 mg/kg) can help to minimize the anticonvulsant effect on the seizure duration.2 Alternatively, propofol has been used for anesthesia in this patient population. However, propofol, a nonbarbiturate anesthetic agent, has also been noted by Rampton et al5 to reduce seizure duration.
Lidocaine, used to treat arrhythmias that might occur during electroconvulsive treatment, also shortens the seizure duration and, if possible, should be used after the electrical stimulus has been administered.6
In contrast to the medications discussed above, many medications have a proconvulsant effect on patients undergoing ECT. Subsequently, their seizure duration will be prolonged. One of the most commonly used medications that can cause this effect is theophylline. Theophylline has been associated with status epilecticus following seizure induction with ECT.2,6 On the other hand, sustained-release theophylline has been recommended for patients who have experienced gradual diminution of the seizure duration.
Swartz and Lewis' reported on their experience using sustained-release theophylline on the evening prior to electroconvulsive treatment in eight patients who had short seizures. Giving sustainedrelease theophylline, 200 to 400 mg the night before, increased the seizure duration an average of 13.9 seconds. None of the patients experienced prolonged seizures. This was attributed to the established high seizure threshold and the low dose of theophylline used. The authors noted that their study only looked at patients who had undesirably short seizures who would be at low risk of experiencing extensive prolongation of seizures from a proconvulsant agent.
Interesting research has been reported in recent years on the beneficial effect of intravenous caffeine in prolonging seizure duration. Caffeine, like other methylxanthines, is a stimulant of the central nervous system.3(p620)
In a randomized double-blind placebo-controlled pilot study of 40 depressed inpatients, Coffey and Figiel8 found that caffeine administered intravenously prior to ECT was as efficacious as increasing stimulus intensity to maintain seizure duration. The main side effect noted in the patients given caffeine was an increase in the rate pressure product (a measure of myocardial oxygen consumption) in the initial treatments; this effect diminished by the fifth or sixth treatment and was not clinically significant. Seizures lasting longer than 200 seconds occurred during three of the ECT treatments and one of these patients subsequently was treated with intravenous methohexital. None of these patients experienced adverse sequelae.
Jaffe et al9 reported on three elderly patients who experienced cardiac dysrhythmia when caffeine was used in conjunction with ECT. They suggested using nonpharmacologic methods for increasing seizure duration in elderly patients with cardiac histories.
Other medications with potential to prolong seizure duration include lithium, tricyclic antidepressants, neuroleptic agents, trazodone, bupropion, and fluoxetine.
MEDICATIONS AND CNS EFFECTS OF ECT
Medications may also have an impact on the degree of confusion experienced as a patient emerges from anesthesia after ECT When lithium is used in close proximity to the onset of ECT, it has been associated with prolonged severe post-ECT confusion and electroencephalographic seizure activity.10 Lithium has an effect on the intracellular production of acetylcholine and may potentiate the action of succinylcholine and other neuromuscular blocking agents.11 Anticholinergic agents are also known to cause confusion.
Medications may also be used to control ECT emergence delirium. An interesting study reported by Swartz12 suggests that ECT emergence delirium may be attenuated by increasing the dose of succinylcholine given prior to ECT. One of the postulated mechanisms of action for this effect is that by increasing the dose of succinylcholine, the patient generates smaller peripheral concentrations of lactate and catacholamines. The author notes that patients who experience emergence agitation may be sensitive to the lactate produced by muscle metabolism during ECT Lactate has been noted to cause panic in patients and may contribute to the confused state a patient experiences following ECT In Swartz's study, five patients had the dose of succinylcholine increased from 0.7 mg/km to 1.0 mg/km. All of the patients were noted to have resolution of their emergence agitation with the increased dose of succinylcholine. While this is a small sample, our preliminary experience using increased doses of succinylcholine has been promising (unpublished data).
MEDICATIONS AND CARDIOVASCULAR SYSTEM RESPONSE TO ECT
ECT results in profound alterations in heart rate and blood pressure. Although the mortality rate from ECT is low, cardiac events are the most common cause of mortality.11 ECT is often performed on elderly patients who have preexisting cardiac conditions and hypertension. ECT causes a pronounced sympathetic effect on the heart, which results in tachycardia, hypertension, and cardiac arrhythmias.13 Beta blockers are commonly used to offset these effects in patients who have known cardiovascular disease.
Stoudemire et al14 evaluated the effects of labetalol in a randomized doubleblind placebo-controlled crossover study. They found that in 11 elderly patients with depression and cardiovascular disease, labetalol was found to blunt mean arterial pressure increase by up to 8.26% and heart rate increase by up to 26.079?-. The frequency of atrial arrhythmias was blunted by up to 100% and premature ventricular contractions by 41.97%. The patients appeared to tolerate the treatment well. The authors suggested that this agent used prophylactically decreased cardiovascular stress during ECT in a medically ill population.
Drop and Welch11 extensively reviewed the practice of anesthesia in the electroconvulsive treatment of patients with cardiovascular risk factors. They noted that the commonly used psychotropic medications can be problematic for these patients. Monoamine oxidase inhibitors (MAOIs) block the oxidated deamination of naturally occurring amines and may cause an intensified sympathetic response in patients being treated with ECT In their review of the literature, they noted that patients did not require a two-week washout period between withdrawal of MAOIs and onset of ECT They suggested that MAOIs should be discontinued at least 24 to 48 hours before ECT and, in the event of arterial hypotension, volume infusion was recommended.
Tricyclic antidepressants have cardiovascular side effects including tachycardia, orthostatic hypotension, intraventricular conduction abnormalities, and arrhythmias. Two reviews of drug interactions and ECT note that concurrent administration of tricyclic antidepressants and ECT may not cause increased cardiovascular toxicity.10,11
Other agents have been noted to cause cardiovascular effects in patients receiving ECT Reserpine may cause cardiovascular collapse or respiratory depression with death or near death. The effects of digitalis on conduction and ventricular irritability may be potentiated by succinylcholine.10
Many medications can interact with ECT, resulting in alterations in seizure duration and generalization, increased potential for confusion, and changes in the cardiovascular response. These are the major effects that clinicians commonly encounter in the practice of ECT. Attention to the patient's medication regimen prior to initiating ECT is an essential step in optimizing the efficacy and safety of ECT. Fortunately, we are able to take advantage of some of the pharmacologic properties of medications to assist us in improving the safety and efficacy of ECT, such as the use of labetalol to decrease the cardiovascular side effects of ECT, and of caffeine to prolong seizure duration. Other medications can interact with the anesthetic agents used for ECT, and a careful review also must be performed by the anesthesiologist. Please refer to the article by M. Weglinski in this issue.15
Despite the fact that many patients coming to ECT are elderly and on multiple medications that alter the seizure threshold, effective ECT administration is possible. A better understanding of seizure activity has resulted in new research, which addresses the problem of inhibited seizure duration and proposes identifying medications that may be used to prolong seizure duration. Research has been focused on which medications decrease the efficacy of the seizure by altering the seizure threshold. In the future, new developments in understanding the interactions of medications and ECT will help provide clinicians with a better understanding of which medications to avoid during ECT and which medications to use for the best possible clinical outcome.
1. American Psychiatric Association Task Force on ECT. The Practice of ECT: Recommendations for Treatment. Training, and Privileging. Washington, DC: American Psychiatric Association Press, Ine; 1990.
2. Sackeim HA. Devanand DP, Prudic J. Stimulus intensity, seizure threshold, and seizure duration: impact on the efficacy and safety of electroconvulsive treatment. Psychialr Clin North Am. 1991; 14(41:803-843.
3. Oilman AG. Goodman and GiIm ans: The Pharmacologic Basis of Therapeutics. 8th ed. Elmsford, NY: Pergamon Press; 1990.
4. Pettinati HM, Stevens SM. Willis KM. Robin SE. Evidence for less improvement in depression in patients taking benzodiazepines during unilateral ECT. Am J Psychiatry. 1990; 147:1029-1034.
5. Rampton AJ, Griffin RM, Stuart CS, Durcan JJ, Huddy NC, Abbott MA. Comparison of methohexital and propofol for electroconvulsive treatment: effects on hemodynamic responses and seizure duration. Anesthesiology. 1989: 70:412-417.
6. Klapheke MM. Potential drug-ECT interactions, part II. Biologic Therapies in Psychiatry Newsletter. 1991; 14:37-40.
7. Swartz CM, Lewis RK. Theophylline reversal of electroconvulsive treatment seizure inhibition. Psychosomatics. 1991; 32:47-51.
8. Coffey CE, Figiel GS, Weiner RD. Saunders WB. Caffeine augmentation of ECT. Am J Psychiatry. 1990; 147:579-585.
9. Jade R. Brubaker G. Dubin WR, Roemer R. Caffeine associated cardiac dysrhythmia during FCT: report of three cases. Convulsive Therapy. 1990;6:308-113.
10. Klapheke MM. Potential drug-ECT interactions, part 1. Biologic Therapies in Psychiatry Newsletter. 1991; 14:33-36.
11. Drop LJ. Welch CA. Anesthesia for electroconvulsive treatment in patients with major cardiovascular risk factors. Convulsive Therapy. 1989:5:88-101.
12. Swartz CM. ECT emergence agitation and succinylcholine dose. J Nerv Ment Dis. 1990; 178:455-457.
13 Welch CA, Drop LJ. Cardiovascular effects of ECT. Convulsive Therapy. 1989: 5:35-43.
14 Stoudemire A, Knos G, Gladson M, et al. Labetalol in the control of cardiovascular responses to ECT in high risk depressed medical patients. J Clin Psychiatry. 1990; 51:508-512.
15. Weglinski M. New anesthetic agents used in electroconvulsive therapy. Psychiatric Annals. 1993; 23:23-26.
Medications and Seizure Activity