6.1.1
Introduction
Electroconvulsive therapy (ECT) is a biological treatment which involves the electrical induction of seizures as treat- ment for psychiatric disorders. Among various indications for its use, ECT remains the gold standard treatment for major depressive disorder.
6.1.2
History of ECT
In 1934, the Hungarian neuropsychiatrist Ladislas Joseph von Meduna chemically induced repeated seizures using camphor in a small series of patients with schizophrenia. He used this to support his theory of the biological antagonism between schizophrenia and epilepsy [1].
In 1937, the Italian neuropsychiatrists Ugo Cerletti and Lucio Bini began to induce seizures experimentally with electrical stimuli in patients with severe psychosis in an attempt to overcome problems associated with camphor, such as pain and variable efficacy [1]. ECT quickly replaced pharmacoconvulsive therapy throughout the world given its greater tolerability.
The use of ECT peaked from the early 1940s through the mid-1950s, when pharmacological antipsychotic and antide- pressant medications were discovered and came into clinical use. It was around this time that ECT also became the subject of highly negative portrayals in the media and its use gradu- ally began to decline [2].
By the mid-1980s, innovations in ECT technique, includ- ing the use of anesthesia, oxygenation, muscle relaxation, and seizure monitoring, led to a growing acceptance of this treatment modality. Physicians began to realize that some patients were intolerant to pharmacological agents and/
or had symptoms that were treatment-refractory. The rapid onset of action of ECT compared to alternative treatments also further contributed to its newly increased use. Presently, over 100,000 patients annually receive ECT treatments in the USA [3].
6.1.3
The Electrical Stimulus
The goal of ECT is to induce a generalized tonic-clonic sei- zure via the delivery of an electrical stimulus. Ideally, this is done in a way that minimizes adverse effects, particularly with respect to memory disturbance. The electrical stimulus is given using alternating current, with a variety of wave- forms. A waveform refers to the shape of the stimulus as a function of time. Historically, sine wave used to be the most common waveform used in ECT; this has been replaced by brief pulse and ultrabrief pulse waveform in modern ECT protocol.
Sine-wave currents are characterized by a continu- ous stream of electricity that flows in alternate directions
(alternating current). Like sine wave, brief pulse is also bidirectional, but instead of the continuously undulating sine wave, brief pulse consists of a series of rising and fall- ing rectangular pulses of current which are separated by brief periods of no baseline electrical activity.
Pulse width refers to the duration of each pulse. Wider pulse widths are less efficient at inducing seizures and are therefore associated with higher seizure thresholds. They are also associated with a greater impact on cognition than nar- rower pulse widths. Stimuli between 0.5 and 2 milliseconds are called brief, and those less than 0.5 milliseconds are known as ultrabrief. The number of pulses per second is referred to as the frequency of stimulus and is measured in Hertz (Hz).
Seizure threshold refers to the total amount of electricity required to induce an adequate seizure and is an integral part of stimulus dosing in ECT. Evoking a generalized seizure using a brief pulse waveform typically requires much less stimulus intensity compared to a sine-wave stimulus.
The electrical stimulus is characterized by current, volt- age, and impedance. Current refers to the number of elec- trons per second flowing through the ECT device, stimulus cables, electrodes, and the patient. Voltage is the force that drives the flow of electrons during the stimulus, and imped- ance refers to the level of resistance to the current flow that needs to be overcome. The greater the impedance, the greater the voltage that is required for the flow of electrons.
The primary source of impedance is scalp tissue that underlies the electrodes. Most of the electrical stimulus is dissipated in the scalp and skull; only a small fraction of stim- ulus energy actually reaches the brain. Impedance can be too high when the stimulus electrodes are in poor contact with the skin, when there is faulty connection of the electrodes, or when the scalp is poorly prepared for ECT. Modern devices have safety mechanisms so that the user cannot deliver the stimulus if the impedance is too high. It is possible for the impedance to be too low, indicating a short circuit. Too-low scalp impedance can occur when the ECT electrodes are placed too close together or when a conducting medium like electrode gel forms a low impedance pathway between the electrodes.
All modern ECT devices utilize a bidirectional, constant- current, brief pulse stimulus waveform. This waveform is more efficient than the older sine wave for inducing seizures and allows ECT to be administered with fewer adverse cog- nitive effects [4]. The use of the ultrabrief pulse, which is a more efficient way to induce seizures stimulus, is associated with less memory impairment. It may also be associated with a slightly more delayed and less robust antidepressant effect, although evidence to support its use is accumulating [5]. .Figure 6.1 shows examples of waveforms used in ECT.
6.1.4
Electrode Placement
The electrical stimulus can be delivered through a variety of electrode placements. Standard electrode placements used in modern ECT practice will be described further.
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In bifrontal placement, the center of each electrode is placed 5 cm above the outer canthus of the eye along a ver- tical line perpendicular to a line connecting the pupils. In bitemporal placement, the center of the stimulus electrodes is applied 2–3 cm (1 inch) above the midpoint of the line con- necting the outer canthus of the eye and the external auditory meatus on each side of the patient’s head. In right unilateral (d’Elia) placement, one electrode is positioned as in bitempo- ral on the right side, and the center of the other electrode is placed 2–3 cm to the right of the vertex of the skull, on a line connecting the tragus of the ear on both sides (see .Fig. 6.2).
Stimulation on the right side of the brain spares the dominant hemisphere from direct stimulation, thus per- haps sparing verbal memory. This works for right-handed patients. However, even in patients who are left-handed, lan- guage function is usually located on the left side of the brain.
Because language function is predominantly located in the left hemisphere in approximately 98% of right-handed peo- ple and in 70–90% of left-handed people, it is reasonable to perform unilateral ECT on the right side, even in left-handed patients. If the patient experiences unusual severe confusion or memory impairment after the first few treatments, consid- eration can be given to switching to left unilateral electrode placement. A simple test of hemispheric dominance can be done by comparing the time elapsed following an ECT treat- ment until the patient can name simple objects [6].
6.1.5
Stimulus Dosing
The seizure threshold is the amount of energy necessary to evoke a generalized seizure. For a therapeutic seizure, the minimum recommended duration of the seizure is 20 seconds of motor response or 25 seconds of electroen- cephalogram (EEG) seizure. This is a rule of thumb to which there are exceptions. Shorter seizures late in the treatment course may still be effective despite their short duration, and shorter seizures at higher stimulus intensities can also be effective. Determination of treatment adequacy is based
on clinical outcome rather than the number of seconds of seizure activity. Seizures tend to be shorter in older patients and to diminish in length over the course of treatment [7].
Seizure duration may also be affected by other parameters including dose of the anesthetic agent used and the amount by which the stimulus exceeds the seizure threshold.
There are many factors which influence an individual’s seizure threshold, including age, sex, placement of stimu- lus electrodes, concomitant psychotropic medications, and
Sine wave Brief pulse Ultra brief pulse
Time (millisecond) Time (millisecond)
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
Time (millisecond) 0 2 4 6 8 10 12 14 16
Intensity Intensity Intensity
.Fig. 6.1 Examples of waveforms used in ECT
.Fig. 6.2 Right unilateral electrode placement Somatic Therapies: Electroconvulsive Therapy
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anesthetic agents. These are listed in .Table 6.1. Age is one of the principal factors affecting seizure threshold; there is, how- ever, significant interindividual variation in this parameter.
There are various methods of determining the dosing of the electrical stimulus. The preferred method in most cases is stimulus dose titration, in which the seizure threshold is deter- mined empirically by a series of stimuli of increasing intensity, and the treatment is given at a predetermined multiple of the seizure threshold (1.5 × threshold for bitemporal/bifrontal ECT, 6 × threshold for right unilateral ECT). This method allows for the most accurate determination of the energy required for effective ECT for an individual, minimizing the energy administered and therefore minimizing cognitive side effects. It is, however, associated with some risks. It requires multiple subconvulsive stimuli, which increase the risk of bra- dycardia or asystole. It may also mean that the first treatment is less effective. This method requires efficiency on the part of the ECT practitioner to ensure that the patient has a seizure during the first treatment session. On average, however, only one restimulation is necessary at the first treatment [8].
Other methods of determining the dose of ECT include age-based dosing in which the dose of ECT is estimated based on a patient’s age and on the desired electrode placement and fixed high dose, in which all patients receive the same dose of stimulus, usually at a relatively high level (e.g., 50–100%
of the device’s maximum output intensity) [9]. These tech- niques do not match stimulus intensity with seizure thresh- old and may result in stimulation of many patients at doses much higher than seizure threshold, as well as potentially underdosing patients receiving right unilateral ECT. They are associated with greater simplicity on the part of users, however, and reduce the risk associated with subconvulsive stimuli.
Older patients are more vulnerable to the cognitive side effects of ECT and are also more likely to have conditions associated with risk for cardiac arrhythmias. Under most circumstances, stimulus dose titration and careful collabora- tion with the anesthesiologist regarding the management of bradyarrhythmia risk are the recommended approaches for older patients.
6.1.6
Seizure Monitoring
Following delivery of the electrical stimulus, monitoring of the generalized seizure is done by observing both the ictal motor response and the EEG activity. In the first phase of the ictal motor response, a gradual, sustained tonic contraction usually occurs within a few seconds after termination of the stimulus and may last from a few seconds to many seconds.
It is then followed by the clonic phase characterized by rhyth- mic alterations in flexion and extension that decrease in fre- quency and then terminate. This phase typically lasts longer than the tonic phase.
Motor activity can be influenced by the dose of muscle relaxant, usually succinylcholine, and intensity of the elec- trical stimulation. Response to stimuli barely above thresh- old may sometimes be decreased or absent, and convulsive movements may not always end simultaneously in all loca- tions [10]. The American Psychiatric Association in 1990 recommended that the end of the motor convulsion be determined by the longest-lasting motor activity observed anywhere in the body [11].
Two EEG leads are generally monitored, one on each side of the head. In this way, seizure activity in both hemispheres is monitored separately. Electrodes are placed over the prefrontal and mastoid areas on the same side of the head.
Contact between the electrode and scalp must be optimized by cleaning the recording electrode sites. ECT devices gen- erally begin recording following the administration of the electrical stimulus.
Preictal baseline recordings often consist of mixed fast and slow activity that may be higher in amplitude than that observed during the waking state. Following the electrical stimulus, sometimes a brief preictal period of low amplitude fast activity may be observed. This may be followed by rhyth- mic activity of low to moderate amplitude, known as the epi- leptic recruiting rhythm, associated with the early stages of seizure generalization. Both the preictal and epileptic recruit- ing rhythm phases are frequently absent. Often the earli- est phase of the seizure is characterized by high frequency polyspike activity. It coincides with tonic and early clonic components of the motor response and lasts 10–15 seconds.
During the clonic phase, this polyspike activity evolves into a repetitive polyspike and slow wave complexes, synchronous with clonic movements. The frequency of these discharges is usually 3–5 Hz and diminishes gradually in frequency as the clonic phase progresses toward termination. In this phase, the amplitude and regularity of the polyspike and slow wave pattern gradually diminish and may end abruptly. The
.Table 6.1 Factors influencing seizure threshold Factor Lower seizure
threshold Higher seizure
threshold
Age Younger Older
Sex Female Male
Brain disease Irritative Diffuse, nonirritative Electrode
placement
Unilateral Bilateral
Electrode application
Good application Poor application Medication Alcohol or benzodiaz-
epine withdrawal Amphetamines Lithium
Tricyclic antidepressants Reserpine
Anticonvulsants Barbiturates Benzodiazepines
Seizure activity
Seizures within last few minutes
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postictal phase begins immediately following EEG seizure termination and usually appears flat. A sample EEG seizure termination appears in .Fig. 6.3.
6.1.7
Mechanism of Action
The exact mechanism by which ECT exerts its antidepres- sant and antipsychotic actions remains unknown. It is widely hypothesized that ECT works by promoting the increased availability of neurotransmitters including serotonin, norepi- nephrine, and dopamine at the synapse with subsequent mod- ulation of postsynaptic receptors, analogous to the mechanism of action of many antidepressants. Anticonvulsant effects of ECT may also be central to the antidepressant properties of ECT [12]. It is also suggested that there is a correlation between both decreased cerebral blood flow and increased interictal prefrontal EEG and clinical response to ECT [13]. Restoration of normal patterns of activity in brain networks may play an important role in the mechanism of efficacy of ECT.
6.1.8
Cardiovascular Response to ECT
Following the initial electrical stimulus, parasympathetic acti- vation occurs due to the direct stimulation of the brainstem nuclei. This results in a drop in blood pressure and transient sinus bradycardia (which lasts several seconds). As soon as the seizure begins, sympathetic nervous system activation begins which causes blood pressure and heart rate to increase dramat- ically. This continues until the end of the clonic phase when parasympathetic system is reactivated. Upon the patient’s awakening, these events are then followed by a second phase of sympathetic hyperactivity. Usually, vital signs return to baseline within minutes of the end of the ictal period.
6.1.9
Pre-ECT Evaluation
ECT operating psychiatrists, medical consultants, and anes- thesiologists must work collaboratively both prior to and during a course of ECT. Basic components of the pre-ECT evaluation should include a thorough psychiatric history including history of previous response to ECT; a medical history and physical examination with focus on cardiovas- cular, respiratory, neurological, and musculoskeletal systems;
a history of dental problems and examination for loose or
missing teeth; and a history of anesthesia use both person- ally and within the family [14]. Any personal or family history of complications from anesthesia should be noted.
Although there is no specific set of routine investigations recommended, laboratory tests generally performed include a complete blood count, serum chemistry with sodium and potassium, as well as an electrocardiogram. A chest x-ray is indicated in patients with cardiovascular or pulmonary dis- ease or with a history of smoking [15].
Decisions regarding additional investigations prior to ECT should be individualized. Testing of cerebral function- ing including electroencephalographic (EEG), neuroimaging, or neuropsychological assessments can be considered where there are specific concerns. Spinal radiographs should also be considered in patients with known or suspected spinal disease. When the risks of ECT in the setting of the existing systemic medical disease are unclear, further testing and/or consultation should be considered.
An evaluation of the risks of cognitive impairment should be considered in every case pre-ECT. The Mini Mental State Examination (MMSE) is the most commonly used bedside rating scale to monitor global cognitive changes [16]. It may however not be very sensitive to changes in anterograde or retrograde amnesia [17]. Other, more sensitive tests such as the Montreal Cognitive Assessment (MoCA) also have limitations with respect to the time associated with admin- istration, learning effects, and lack of specificity to autobio- graphical memory loss. The pre-ECT cognitive evaluation and the patient’s values and preferences should guide recom- mendations about treatment technique in terms of electrode placement, treatment frequency, dosing, and medications to be avoided. Cognition and autobiographical memory should be monitored during ECT, both by clinical history and by objective measures according to the clinician’s judgment.
6.1.10
Informed Consent
Informed consent in the geriatric population requires spe- cial consideration because decisional capacity to consent to ECT treatment may be compromised from cognitive dys- function or severe psychiatric illness [18]. The process of informed consent begins with the provision of information about the ECT treatment and signing of the consent docu- ment. Written consent is the standard for ECT. This process continues throughout the entire course of ECT treatment;
it should be made clear that the patient or their surrogate
er) EEG #2 0.050 mV/mm (Trace 2-Lower)
^00:29 ^00:30 ^00:31 ^00:32 ^00:33 ^00:34 ^00:35 ^00:36 ^0 EEG #1 0.050 mV/mm (Trace 1-Upper)
.Fig. 6.3 EEG seizure termina- tion
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(substitute) decision maker can withdraw consent at any time. It is the responsibility of the operating psychiatrist to ensure that the appropriate information has been conveyed regarding risks and benefits specific to that patient and that the patient has had a chance to ask questions about the pro- cedure. The physician should provide information about the nature of the condition being treated; a description of how, when, and where ECT will be performed; typical numbers of treatment sessions; and the expected benefits and possible risks of ECT including death, cardiac complications, and cognitive impairment. Information should also be provided about practical considerations during the course of ECT, including taking nothing by mouth after midnight prior to the day of treatment and that emergency treatment may be necessary if the patient has a complication during an ECT treatment. The physician should also confirm that the patient has understood the information provided as well as appre- ciates the benefits and risks of other reasonable alternative treatments or no treatment. Consent to ECT must be volun- tary and must be obtained from the patient unless the patient is considered decisionally incapable. In some jurisdictions, surrogate consent for involuntary ECT for a decisionally incapable patient is not allowed under the law, and a formal judicial consent may be needed. For incapable patients, sur- rogate consent should be obtained prior to treatment with ECT in accordance with the legal requirements of the local jurisdiction. The discussion should be documented in the patient’s medical record.
6.1.11
Management of Medications
In treatment of major depressive disorder, combining ECT with an antidepressant such as venlafaxine or nortriptyline can improve remission rates by approximately 15% [19].
Some psychotropic medications are probably best avoided or maintained at the lowest possible doses during ECT.
Lithium may increase the risk of delirium or prolonged sei- zures, and so in general it is preferable to discontinue this medication prior to ECT sessions. Data from case series suggests that lithium continuation during a course of ECT can be done without is held 24–36 hours before each ECT treatment session. The decision to continue lithium dur- ing a course of ECT, particularly in specific patients with a
“brittle” depressive disorder, should be carefully considered by the treating psychiatrist [20]. Due to the anticonvulsant property of benzodiazepines and antiepileptic medications, it can be more difficult to induce a seizure, and efficacy of ECT may be decreased. If it is impossible to discontinue benzodiazepines during ECT, their action can be reversed with flumazenil just prior to the procedure, with careful attention to the possibility of withdrawal. The use of anticon- vulsants during ECT depends upon the indications for use and upon the particular drug in question. ECT can be done in the presence of anticonvulsant medications, with careful observation of the adequacy of the seizure in ECT and of the
patient’s clinical response. If possible, the use of anticonvul- sant medications should be minimized during ECT. Where it is deemed necessary to continue anticonvulsants during ECT, using the minimum effective dose and timing the ECT procedure to coincide with trough levels of the drug can be helpful strategies. Other drugs that lower seizure threshold (e.g., clozapine, bupropion, tricyclic antidepressants) may slightly increase the risk of prolonged seizures, especially when used in combination. It is usually safe to consider such medications during ECT, but caution should be exercised regarding high doses and polypharmacy.
Most medications scheduled to be administered in the morning are held until after the procedure. However, anti- hypertensive medications, cardioprotective medications, and anti-reflux medications are usually given in the morning prior to the procedure with sips of water. Diuretics should not be given prior to ECT because of the risk of inconti- nence and/or bladder rupture. Decisions regarding pre- ECT medications should be made in collaboration with the anesthesiologist.
6.1.12
Use of ECT in Geriatric Psychiatry
A large proportion of patients receiving ECT are in the geri- atric age range [21]. Several factors may be attributed to the higher rate of ECT utilization in the older population.
Depressive disorders can increase in severity and frequency with increasing age as the natural history of major depressive illness progresses [22]. There is also an association between high relapse rates and later onset of illness [23]. Due to age- related pharmacokinetic changes, geriatric patients have a lower tolerance to medications and are sometimes unable to tolerate adequate pharmacotherapy. In comparison to phar- macotherapy, ECT may pose less risk of complications in older patients [11]. Geriatric patients also tend to have a bet- ter response to ECT, with higher rates of response and remis- sion than their younger counterparts. Finally, older patients have less physiological reserve and can quickly deteriorate into life-threatening situations when they stop eating and drinking and become bedbound or immobile in the context of severe depressive disorder.
6.1.13
Diagnostic Indications and Efficacy
Major Depressive DisorderLate-life depressive disorder is a serious and growing psychi- atric problem. It is a common psychiatric disorder in older adults and is associated with substantial morbidity and mor- tality. It also impairs quality of life and creates a substantial strain on families and communities.
The efficacy of ECT in major depressive disorder is well established [24]. It is effective in treating both melancholic and severe non-melancholic depressive disorder [25] as well as bipolar depression [26]. It has particular efficacy in treating
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