Electroconvulsive therapy: a review of history, patient selection, technique, and medication management.

Abstract: Electroconvulsive therapy (ECT) is a safe and effective treatment for severe and persistent depression, bipolar disorder and schizophrenia. Though ECT is now over 60 years old, it remains an underutilized treatment today. History, patient selection, safety, and characteristics of the treatment stimulus, technique, and medications used in ECT are reviewed. Dosing strategies, as pertaining to seizure threshold, will be considered. Mechanisms of action, especially with regard to serotonin, norepinephrine, and dopamine receptor expression will be discussed.

Key Words: electroconvulsive, seizure, depression, bipolar disorder, schizophrenia

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Electroconvulsive therapy (ECT) has been shown to be a highly effective, safe, and even life-saving treatment for persistent and severe depression, bipolar disorder and schizophrenia. Over 50,000 ECT treatments are performed annually in the United States. (1) The history of ECT, clinical indications for ECT, patient outcomes, current practices in ECT administration, patient workup, and post ECT care will be reviewed.

History

Convulsive therapy, relevant to the practice of psychiatry, has its origins in the work of Ladislaus von Meduna. (2) Meduna used pentylenetetrazol to induce seizures in patients with catatonic schizophrenia. (1,2) This form of convulsive therapy was wide- spread in Europe in the 1930s. Electricity was used successfully in 1938 by Ugo Cerletti and Lucio Bini for the purpose of eliciting seizures to treat mental illness. In the 1950s, Max Fink, one of the most important figures in the history of ECT, was the first to apply rigorous scientific research methods to ECT, which gave the treatment scientific legitimacy. (2)

The anti-psychiatry movement and the promise that pharmacology would cure mental illness contributed to a decline in ECT use in the ensuing decades. The anti-psychiatry movement was largely a by-product of popular philosophical ideology of the time, negative views that mental illness was a mere invention, and negative views of ECT as a brutal practice. In spite of negative media depiction (the movie One Flew Over the Cuckoos Nest, for example) contributing to a decline in ECT use, ECT has shown a strong comeback in the last decade, which is a testament to its continued efficacy and safety. (3,4)

Patient Selection

It has long been known that ECT is an appropriate treatment for medication resistant depression. Patients who have shown no response to pharmacotherapy, or psychotherapy, will still respond to ECT at a rate that approaches 55%. (4) Recent studies have demonstrated that ECT is highly effective for the initial treatment of depression as well. The response rate for index depression has been reported as high as 80 to 90%. (1) Index depressions have been defined as depressive episodes that are currently occurring, with a discernable beginning and a clear history of the patient experiencing normal mood states before the onset of depression. These data have led the APA to recommend that the use of ECT be considered as an initial treatment option, in certain cases, for patients with severe depression. (5)

For all patients treated with ECT, it should be stressed that ECT represents a treatment that will bring remission, not a cure, and in many cases, maintenance ECT should be discussed with patients because the effects of ECT are transient. (5) These caveats are in part due to the nature of the treatment itself, as well as the remitting nature of the illnesses for which ECT is effective. The APA recommends that the patient receive ECT once a week for a month following the initial treatment. Subsequent maintenance treatments should be scheduled according to clinical judgment, patient preference, and with regard to the patient's history of previous illness relapses. (5)

ECT has been approved for the treatment of bipolar illness in mania, depression, and mixed states. ECT has also been shown efficacious in the treatment of schizophrenia with pharmacotherapy as psychotic symptom relapse prevention. (6)

Mechanism of Action

Though ECT has proven efficacy and safety, the mechanism of action is difficult to elucidate. A full discussion of the proposed mechanisms of action is well covered elsewhere. (2) There are three mechanisms that seem to hold the most favor among researchers: 1) Modulation of monoamines, 2) Change in neurotrophic factors, and 3) Anticonvulsant factors. (2,7)

It has been shown that monoamine levels increase in animal models treated with ECT. (8,9) It may also be that increases in serotonin levels have an indirect impact on levels of endogenous opioids. (9) The increase in dopamine levels with ECT may explain why ECT improves symptoms of Parkinson disease. (10)

Little is known about the intracellular impact of ECT, though researchers have looked at neurotrophic mechanisms and possible relation to therapeutic response. This theory of neurotrophic mechanism states that cyclic AMP (cAMP) is up regulated with ECT, (8) which increases brain derived neurotrophic factor (BDNF). (11) BDNF regulates neuron cell strength, growth and survival, as well as norepinephrine and serotonin receptor expression.

Increase in GABA transmission and receptor antagonism has been observed in ECT. (12) This anticonvulsant action raises the seizure threshold during ECT. Also, ECT causes an increase of endogenous opioids that may also have anti-seizure properties.

Safety and Side Effects

Much of the current bias and controversy surrounding ECT is with regard to safety and side effects. ECT is considered safe, with a mortality of approximately 1/10,000 patients or 1/80,000 treatments. This puts the ECT risk at the level of childbirth or minor surgery. (1) There are no recommendations regarding the total number of ECT treatments. However, some case reports have examined patients who have had thousands of lifetime treatments with no ill effects. (13)

The most commonly expressed worries and criticisms center on memory loss. Anterograde amnesia, or the inability to form new memories, has been reported, though it tends to be short-lived and resolves rapidly within a few weeks of the procedure. (14) Retrograde amnesia, or loss of past memories, tends to affect recent memories more than remote memories. Loss of memories of the events immediately surrounding the procedure is not uncommon and usually resolves within weeks of the treatment. (15) Loss of remote memories is quite rare, and for that reason, is difficult to quantify. Permanent memory loss is extremely rare. (16)

Other reported side effects include headache, nausea, and muscle soreness. Muscle soreness is often due to the use of succinylcholine; however, inadequate muscle blockade also causes muscle soreness. (17) Nausea is common with ECT given that ECT stimulates the vagus nerve. Proton pump inhibitors can be used safely in such patients.

Missed or short seizures can occur. It is also noted that seizure induction can be difficult, particularly in the elderly. In addition to hyperventilation, pharmacologic methods have been shown to be of help. Augmentation with caffeine or switching anesthetic agents may also help. (18,19)

Seizure Characteristics, Dosing, and Frequency of Treatment

ECT functions to induce a seizure, and characteristics of a therapeutic seizure have been reported. Some important points to mention here are: 1) Length of ictal motor response, 2) Length of the EEG seizure, and 3) Intensity of the electrical stimulus.

An appropriate ictal response has been reported to be between 20 to 25 seconds in duration. (1) Direct observation of the ictal motor seizure is the best method of measure; however, newer ECT devices have the capacity to monitor EMG activity, which is recorded by the ECT device and analyzed by the onboard computer (MECTA Corp.; Somatics LLC).

A therapeutic seizure is generally accepted to be one that is greater than 30 seconds in length. (1) During the clonic phase of the seizure, spike and slow waves will be observed on the EEG. Seizure termination will often be followed with post ictal suppression, observed as a flattening on the EEG monitor.

Stimulus intensity has been a topic of much ongoing research and controversy. Current data suggest that a moderately suprathreshold seizure offers the best clinical response for the patient. (20,21) Seizure threshold is difficult to measure in patients; however, newer dosing strategies have improved capacities to determine the seizure threshold with greater accuracy. Research indicates that a seizure stimulus that is 150% above the seizure threshold for bilateral ECT, and 200 to 250% above the seizure threshold for unilateral ECT, offers the best clinical response with the least cognitive impairment. (7,19,20)

Though a complete discussion of different dosing strategies in ECT is beyond the scope of this paper, a brief word about dose titration and other dosing techniques will be offered here. There are three basic approaches to selecting stimulus energies: 1) Pre-selected dosing, 2) Age-based dosing and half-age dosing, and 3) Dose titration.

Preselected dosing involves making an assumption about what stimulus intensity has the best chance of inducing a seizure in the greatest number of patients. Often, the device will be set at 75% of its maximum energy and left there until the energy stimulus is no longer adequate to produce a seizure. A variation of this technique is to use the patient's age as a determinant of stimulus settings. For example, a 30-year-old would start with an energy setting of 30%, or roughly 150 mC. This stimulus dose is continued until it is no longer adequate for seizure production. The half-age method uses an energy setting equal to half the patient's age.

The dose titration method divides the stimuli of the ECT device into 8 levels. The first level is the lowest energy setting of the device. Each subsequent level is approximately 50% greater in energy than the previous level. An assumption of what stimulus intensity has a fair chance of inducing a seizure in a patient is selected first. If the first stimulus dose does not induce a seizure, then the next level is selected, and so on. This method often fails to produce a seizure on the first stimulus, but it does help the clinician narrow the range of energy that is required to induce a seizure. On subsequent treatments, the energy is increased, as stated earlier, to achieve a moderate suprathreshold seizure. (20,22)

Dosing frequency has differed in the United States and Europe. By convention, ECT is performed three times a week in the US, while in Europe it is performed twice a week. Twice weekly treatments result in slower improvement, decreasing cognitive side effects, while thrice weekly treatments will bring a patient to remission faster. Patients will typically receive between six and twelve treatments with ECT. It is not uncommon for patients to respond after their first treatment, though it can take more than twelve treatments to see an adequate response in some patients. Balance and risk-benefit analysis is always necessary when selecting any treatment strategy for a patient. One must always keep the severity of illness, as well as patient preference, in mind when setting a treatment strategy for ECT.

Electrode Placement

When ECT was first used, the electrodes were placed on either side of the head at the temples. By the mid 1950s, practitioners began to experiment with unilateral electrode placement. The electrodes were placed over the nondominant hemisphere, which resulted in less post treatment confusion and memory loss. Though somewhat controversial, right unilateral electrode placement has been demonstrated to be as effective as bilateral placement in some studies; however, higher stimulus intensity is needed to achieve a therapeutic response. (1,22)

Medications in ECT

ECT was performed without anesthesia in the first several years of its use, but by the late 1950s, anesthesia had become commonplace. Early use of barbiturates carried the risk of cardiac arrhythmias, as well as decreasing seizure duration. (23) Today, methohexital, a short-acting barbiturate, has become the anesthetic of choice among ECT practitioners. Though barbiturates increase seizure threshold and decrease seizure duration, among barbiturates, methohexital appears to have the least impact on these factors.

The use of muscle blockers has greatly reduced the likelihood of physical injury during ECT. (17,24) The drug of choice among psychiatrists and anesthesiologists is succinylcholine. This drug has a quick onset of action, is short-acting, and does not need to be reversed, as is the case with many non-depolarizing blockers.

ECT causes a significant change in autonomic function. Initially, the patient experiences a parasympathetic surge, which can cause significant bradycardia, hypotension, and, in some cases, brief asystole. (25) To prevent this, anticholinergic drugs such as glycopyrrolate are often used. Although atropine has been the drug of choice in the past, glycopyrrolate offers the advantage over atropine in that it does not cross the blood-brain barrier and therefore does not cause unwanted cognitive side effects. (24)

Drug Interactions in ECT

There are a few drug interactions with ECT that are worthy of some discussion. Anticonvulsant medications, which are commonly used in the psychiatric patient, act to raise the seizure threshold and decrease the length of the seizure. (26,27) As data are making it clear that efficacy is linked to the degree to which the seizure exceeds the seizure threshold, anticonvulsants may increase the seizure threshold in some patients, such that the seizure will no longer be therapeutic. Stopping the anticonvulsant is advised if it can be done safely. If it is not possible to stop anticonvulsant medications, then decreasing the dose to the lowest therapeutic level is recommended.

Lithium, a drug commonly used to treat bipolar disorder, has the potential to both increase seizure duration and cause intense postictal confusion. Though a full discussion of the proposed mechanism of action is beyond the scope of this paper, a previous study has examined this in some detail (28) showing that the concomitant use of lithium with ECT is not recommended.

Theophylline is a drug that can increase seizure duration and increase the risk of status epilepticus. Discontinuation of the medication is advised. If the patient cannot stop the medication, then decreasing it to the lowest therapeutic drug level will at least decrease the risk of interaction with ECT. (29)

Patients who are taking a benzodiazepine should stop the medication before ECT, if possible. Benzodiazepines increase the seizure threshold, decrease seizure duration, and consequently decrease the potential efficacy of ECT. If stopping benzodiazepines does not seem wise or possible, then the use of flumazenil just before ECT can temporarily reverse the effects of benzodiazepines.

Workup and Patient Considerations

The APA recommends that each patient receive a complete psychiatric and medical evaluation before ECT. No specific recommendations regarding laboratory workup exist; however, a minimum of an electrolyte panel and a complete blood count should be obtained. A thorough history of the illness process, as well as treatments tried in the past, is necessary for a complete evaluation. Patients who have tried ECT in the past with a favorable response have a greater chance of responding to treatment in the future. As stated earlier, patients with medication resistant depression often respond favorably to ECT. However, patients with dysthymia or comorbid personality disorders often do not have a robust response to ECT. (5)

Though there are no absolute contraindications to ECT, some medical conditions do complicate the use of ECT. Care should be used with ECT on patients with space occupying intracranial lesions. Past convention indicated that patients with intracerebral masses should not receive ECT. (30) ECT increases intracranial pressure, as well as a transient increase in blood flow to the brain. Current studies suggest that patients with intracerebral masses that lack a mass effect can safely receive ECT (eg, patients with meningiomas). (31) Head Computed Tomography (CT) is not necessary unless there is clinical suspicion.

Patients with cardiac disease can receive ECT, but evaluation by a cardiologist should be obtained and may help in managing the patient. When considering ECT in patients who have recently had a myocardial infarction, care should be taken to ensure that further damage to the cardiac muscle is not done due to the increased work demands of the procedure. However, ECT does not appear to cause malignant arrhythmias or cardiac ischemia. (32) Patients with cardiac pacemakers may safely receive ECT. A cardiologist should be consulted, as the older demand type pacemakers may need to be converted to a fixed rate pacing or deactivated before ECT. (33,34)

ECT is considered safe in pregnancy. Obstetric consult should be obtained and fetal monitoring used when appropriate. Avoidance of hyperventilating the patient will ensure adequate oxygenation of the fetus during the treatment. In late pregnancy, the patient should lie on her left side, which will ensure adequate blood flow to the fetus. Transmission of anesthetic agents across the maternal fetal barrier is considered to be minimal.

A careful dental examination should be part of the patient workup. Modifications to the bite block may be necessary for chipped or broken teeth. Loose teeth may need to be extracted before ECT to avoid injury to the oral cavity and aspiration.

Patients with gastroesophageal reflux disease may experience worsening symptoms during ECT, as the treatment stimulates the vagus nerve. Antacid medications can be safely used. Patients who are on proton pump inhibitors may safely use them before and after ECT. Some anesthesiologists argue that intubation may be called for in rare cases in which the patient suffers from severe reflux disease.

Post Treatment Considerations

ECT can be done on both an inpatient as well as an outpatient basis. Routine monitoring of vital signs is done for 30 minutes following treatment. A designated ECT suite equipped with blood pressure monitoring, oxygen level assessment, and a crash cart is sufficient for ECT. Access to medications used in ECT, as well as the appropriate medications used to abort prolonged seizures and manage cardiovascular abnormalities, is also needed.

Observation of spontaneous respiration and normal blood pressure is good clinical evidence that the patient is not having a tardive seizure. However, it is good practice to leave the EEG monitor in place for several minutes following treatment so the patient can be monitored for any subsequent seizure activity.

The patient may resume her/his normal activity, as she/he is able. Some practitioners advise against driving on the day of treatment, and others tell patients not to drive until the entire treatment series is complete.

Periodic assessment of the patient's memory should be done. If the patient is having excessive memory problems, then decreasing the frequency of treatments, changing anesthesia, or discontinuation of treatment should be considered.

Medications that have been held during ECT should be resumed after treatment. If a patient with a seizure disorder has been treated and their anticonvulsant medication dose lowered for ECT, increasing the anticonvulsant medication to pre-ECT doses can be done after the ECT series is complete.

ECT is a beneficial treatment for catatonia and neuroleptic malignant syndrome.

Discussion

ECT is a safe and effective treatment option for patients. It has proven efficacy in treating medication resistant depression. It is also an excellent treatment option for patients with severe suicidal ideation. ECT currently exists as an option for patients with bipolar disorder in all phases of the illness. It has proven beneficial in patients with psychosis due to schizophrenia, as well as other related mental disorders.

ECT has been safely used in patients with comorbid medical conditions. Careful management of their medical complications makes ECT relatively safe to use. More modern anesthesia techniques and medications have greatly reduced the morbidity and mortality of ECT.

Although current wisdom has relegated ECT to a last treatment option in many cases, experience and emerging research have made it clear that ECT should be offered to patients as a viable treatment option at all stages of their illness process.

Acknowledgments

Special thanks to Dr. David Casey at the University of Louisville for his guidance in organizing and preparing this manuscript for publication.

References

1. Beyer JL, Weiner RD, Glenn MD. Electroconvulsive Therapy: A Programmed Text. 2nd edition. Washington, DC, American Psychiatric Press, Inc, 2001.

2. Abrams R. Electroconvulsive Therapy. 4th edition. Oxford, Oxford University Press, 2002.

3. Glass RM. Electroconvulsive therapy: time to bring it out of the shadows. JAMA 2001;285:1346-1348.

4. Sackeim HA, Haskett RF, Mulsant BH, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 2001;285:1299-1307.

5. Weiner RD, Coffey CE, Fochtmann LJ, et al. The Practice of Electroconvulsive Therapy Recommendations for Treatment, Training, and Privileging. 2nd edition. Washington, DC, American Psychiatric Association, 2001.

6. Tharyan P, Adams CE. Electroconvulsive Therapy for Schizophrenia. Cochrane Database of Systemic Reviews. (2):CD000076, March 2005.

7. Sadock BJ, Sadock VA. Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 9th edition. New York, Lippincott Williams & Wilkins, 2003.

8. Gur E, Dremencov E, Garcia F, et al. Functional effects of chronic electroconvulsive shock on serotonergic 5-HT(1A) and 5-HT(1B) receptor activity in rat hippocampus and hypothalamus. Brain Res 2002;952:52-60.

9. Benkelfat C. Biochemical effects of electroconvulsive therapy. Encephale 1988;14:273-281.

10. Dam H, Pakkenberg H, Bolwig TG. Electric stimulation (ECT) in Parkinson disease. Ugesk Laeger 1992;154:183-187.

11. Li B, Suemaru K, Cui R, et al. Repeated electroconvulsive stimuli increase brain derived neurotrophic factor in ACTH-treated rats. Eur J Pharmacol 2006;529:114-121.

12. Palmio J, Huuhka M, Saransaari P, et al. Changes in plasma amino acids after electroconvulsive therapy of depressed patients. Psychiatry Res 2005;137:183-190.

13. Devanand DP, Dwork AJ Hutchinson ER, et al. Does ECT alter brain structure? Am J Psychiatry 1994;151:957-970.

14. Moscrip TD, Terrace HS, Sackeim HA, et al. A primate model of anterograde and retrograde amnesia produced by convulsive treatment. JECT 2004;20:26-36.

15. O'Connor M, Brenninkmeyer C, Morgan A, et al. Relative effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy on mood and memory: a neurocognitive risk-benefit analysis. Cogn Behav Neurol 2003;16:118-127.

16. Reid WH Electroconvulsive therapy. Tex Med 1993;89:58-62.

17. Werawatganon T, Kyokong O, Charuluxananan S, et al. Muscular injury after succinylcholine and electroconvulsive therapy. Anesth Analg 2004;98:1676-1679.

18. Datto C, Rai AK, Ilivicky HJ, et al. Augmentation of seizure induction in electroconvulsive therapy: a clinical reappraisal. JECT 2002;18:118-125.

19. Krystal AD, Dean MD, Weiner RD, et al. ECT Stimulus intensity: are present ECT devices too limited? Am J Psychiatry 2000;157:963-967

20. McCall WV, Reboussin DM, Weiner RD, et al. Titrated moderately suprathreshold vs fixed high-dose right unilateral electroconvulsive therapy: acute antidepressant and cognitive effects. Arch Gen Psychiatry 2000;57:438-444.

21. Sackeim HA, Prudic J, Devanand DP, et al. A prospective, randomized double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry 2000;57:425-434.

22. Heikman P, Tuunainen A, Kuoppasalmi K. Value of the initial stimulus dose in right unilateral and bifrontal electroconvulsive therapy. Psychol Med 1999;29:1417-1423.

23. Mokriski BK, Nagle SE, Papuchis GC, et al. Electroconvulsive therapy-induced cardiac arrhythmias during anesthesia with methohexital, thia-mylal, or thiopental sodium. J Clin Anesth 1992;4:208-212.

24. Ding Z, White PF. Anestheisa for electroconvulsive therapy. Anesth Analg 2002;94:1351-1364.

25. Tang WK, Ungvari GS. Asystole during electroconvulsive therapy: a case report. Aust N Z J Psychiatry 2001;35:382-385.

26. Coffey CE, Lucke J, Weiner RD, et al. Seizure threshold in electroconvulsive therapy, II: the anticonvulsant effect of ECT. Biol Psychiatry 1995;37:777-788.

27. Sackeim HA, Decina P, Prohovnik I, et al. Anticonvulsant and antidepressant properties of electroconvulsive therapy: a proposed mechanism of Action. Biol Psychiatry 1983;18:1301-1310.

28. El-Mallakh RS. Complications of concurrent lithium and electroconvulsive therapy: a review of clinical material and theoretical considerations. Biol Psychiatry 1988;23:595-601.

29. Fink M, Sackeim HA. Theophylline and the risk of status epilepticus in ECT. JECT 1998;14:286-290.

30. Krystal AD, Coffey CE. Neuropsychiatric considerations in the use of electroconvulsive therapy. J Neuropsychiatry Clin Neurosci 1997;9:283-292.

31. Kellner CH, Ramas L. Dexamethasone pretreatment for ECT in an elderly patient with meningioma. Clin Gerontol 1990;10:67-72.

32. Takada JY, Solimene MC, da Luz PL, et al. Assessment of the cardiovascular effects of electroconvulsive therapy in individuals older than 50 years. Braz J Med Biol Res 2005;38:1349-1357.

33. Giltay EJ, Kho KH, Keijzer LT, et al. Electroconvulsive therapy (ECT) in a patient with a dual-chamber sensing, VDDR pacemaker. JECT 2005;21:35-38.

34. Dolenc TJ, Barnes RD, Hayes DL, et al. Electroconvulsive therapy in patients with cardiac pacemakers and implantable cardioverter defibrillators. Pacing Clin Electrophysiol 2004;27:1257-1263.

Stephen Taylor, MD

From the Department of Psychiatry and Behavioral Science, University of Louisville School of Medicine, Louisville, Kentucky.

Reprint requests to Dr. Stephen Taylor, Department of Psychiatry, Behavioral Sciences, University of Louisville, School of Medicine, 501 E Broadway, Med Center 1, Suite 340. Louisville, KY 40202. Email: [e-mail]

Accepted December 8, 2006.

RELATED ARTICLE: Key Points

* Electroconvulsive therapy (ECT) has been shown to be a highly effective, safe, and even life-saving treatment for persistent and severe depression, bipolar disorder and schizophrenia.

* ECT is safe for patients with comorbid medical conditions, as modern anesthesia techniques and medications have greatly reduced the morbidity and mortality of ECT.

* Experience and emerging research have made it clear that ECT should be offered to patients as a viable treatment option at all stages of their illness process.