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Arielle D. Stanford, Alexandra Sporn, Andrew D. Krystal, Richard D. Weiner, Sarah H. Lisanby: Chapter 27. Convulsive

and Other Somatic Therapies, in Gabbard’s Treatments of Psychiatric Disorders, 4th Edition. Edited by Glen O. Gabbard.

Copyright ©2009 American Psychiatric Publishing, Inc. DOI: 10.1176/appi.books.9781585622986.257453. Printed

5/10/2009 from www.psychiatryonline.com

Gabbard’s Treatments of Psychiatric Disorders > Part V. Mood Disorders >

Chapter 27. Convulsive and Other Somatic Therapies

INTRODUCTION

Nonpharmacological somatic therapies are among the oldest and the newest biological therapies in

psychiatry. Convulsive therapy dates back to the very beginnings of modern biological psychiatry.

Electroconvulsive therapy (ECT) now approaches its 70th anniversary, and older forms of

chemically induced convulsive therapy date back even further. Novel somatic therapies are being

developed to noninvasively stimulate the brain using electrical or magnetic fields applied through

the scalp (e.g., transcranial magnetic stimulation [TMS], magnetic seizure therapy [MST], and

transcranial direct current stimulation [tDCS]) via stimulation of the vagus nerve (i.e., vagus nerve

stimulation [VNS]), or via electrodes implanted directly into the brain (e.g., deep brain stimulation

[DBS]).

This chapter reviews the state of the art of convulsive and other somatic therapies for mood

disorders, of which only ECT and VNS are approved by the U.S. Food and Drug Administration (FDA)

for the treatment of mood disorders, although TMS is approved in other countries. Information on

evolving somatic therapies illustrates new horizons in potential therapies for mood disorders. These

approaches include TMS, MST, tDCS, and DBS for mood disorders, which are investigational and

off-label in the United States at the time of this writing (Table 27–1).

Table 27–1. Comparison of somatic therapies

Seizure

induction

Type of

stimulation

FDA approved for

depression

Unique aspects

ECT Yes Electrical Yes Unmatched efficacy

Significant side effects

Newer delivery methods resulting in

improve efficacy and tolerability

VNS No Electrical Yes (as adjunctive

treatment in adults)

Long-term treatment (not an acute

treatment)

rTMS No Magnetic Not at the time of this

writing

Noninvasive, focal treatment

Minimal side effects, no anesthesia

MST Yes Magnetic No Potential to retain therapeutic efficacy of

ECT

Focal stimulation

Fewer cognitive side effects than ECT

DBS No Electrical No Circuitry targeted precisely

Deeper brain structures reached than

with magnetic fields or focal ECT

tDCS No Electrical No Noninvasive, portable, and inexpensive

treatment

Few side effects

Note. FDA = U.S. Food and Drug Administration; ECT = electroconvulsive therapy; VNS = vagus nerve

stimulation; rTMS = repetitive transcranial magnetic stimulation; MST = magnetic seizure therapy; DBS =Print: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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deep brain stimulation; tDCS = transcranial direct current stimulation (i.e., direct current polarization).

ELECTROCONVULSIVE THERAPY

ECT, the use of electrically induced seizures for therapeutic purposes, has remained the most

effective antidepressant treatment through its progressive evolution over the past 70 years. In

1938, chemical induction methods were superseded by the safer and more reliable electrical

induction, and the introduction of general anesthesia in the late 1950s reduced morbidity.

Additional technical innovations over the past 30 years have improved ECT administration in

regards to efficacy and side effects.

This section focuses on the use of ECT for mood disorders in contemporary practice. More detailed

information on ECT and on its use in other disorders is available (Abrams 1997; American

Psychiatric Association 2001; Beyer et al. 1998). The American Psychiatric Association (APA) work

provides comprehensive clinical recommendations covering all aspects of ECT, including training

and privileging.

Current Status of ECT

ECT has been shown to be a safe, effective, and at times even lifesaving treatment for severe

psychiatric disorders, including major depression with and without psychotic features, mania,

schizophrenia and schizoaffective disorder, catatonic states, and neuroleptic malignant syndrome

(American Psychiatric Association 2001; Daly et al. 2001; George 2002; George et al. 2002;

Ghaziuddin et al. 2002; Lisanby et al. 2000a, 2003b; Greenhalgh et al. 2005; Sackeim 1986;

Sackeim and Rush 1995). For many patients without adequate response or tolerance to currently

available pharmacotherapy, ECT has proven effective (UK ECT Review Group 2003). About 1–2

million individuals receive ECT each year worldwide, with utilization increasing.

ECT remains the only FDA-approved monotherapy for medication-resistant depression. The value of

ECT has been endorsed by numerous professional societies and other groups, including the APA

(American Psychiatric Association 2001), the National Institutes of Health and Mental Health

(Consensus Conference 1985), and the U.S. Surgeon General (U.S. Department of Health and

Human Services 1999). Over the last several decades, a series of scientific advances in ECT

methodology were made. These advances have made modern ECT a state-of-the-art medical

procedure in which both efficacy and safety can be optimized.

Indications

A referral for ECT can be made on a primary basis for any of the following reasons: 1) an urgent

need (either psychiatrically or medically) for a rapid response (see Case 1, later in chapter), 2)

treatment alternatives associated with a higher risk than ECT (see Case 2, later in chapter), 3) a

history of preferential response to ECT, or 4) patient preference for ECT (American Psychiatric

Association 2001). Most patients, however, are referred for ECT on a secondary basis as a result of

1) lack of adequate response or demonstrated intolerance to treatment alternatives or 2)

deterioration of the patient’s condition to the point at which criteria for primary use are met. The

determination of lack of adequate response (i.e., treatment resistance) is best made individually,

taking into account symptom severity, functional impairment, risks, and patient attitudes, in

addition to the number, duration, type, and dosage of prior medication trials (American Psychiatric

Association 2001).

ECT for Children and Adolescents

ECT is rarely used in children and uncommonly used in adolescents. In such patients, ECT is only

used when medication resistance has been clearly established (Kellner and Bourgon 1998;

Greenhalgh et al. 2005; Petrides et al. 1994; Rey and Walter 1997). Although ECT has been

successfully used in young people for treatment-resistant depression (Rey and Walter 1997; Walter

and Rey 2003; Walter et al. 1999a, 1999b), intractable mania (Carr et al. 1983; Russell et al. 2002),

catatonia (Cizadlo and Wheaton 1995; Ghaziuddin et al. 2002; Slooter et al. 2005), schizophrenia

(Bender 1947), and neuroleptic malignant syndrome (Chungh et al. 2005; Ghaziuddin et al. 2002), Print: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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there is a marked paucity of published data on ECT in youth. Most reports are single cases, and

there are no controlled trials (Segal et al. 2004). However, the systematic review of several

randomized trials of ECT that included both children and adults found that ECT is no less effective in

children and adolescents than in other age groups (Morales et al. 2005).

The infrequent use of ECT in youth may be due to several factors, including reluctance to use more

invasive treatments in youths, concern about potential for adverse cerebral effects while the brain

is still developing (although no clinical data support this contention), and, in some states,

regulations preventing use of ECT in patients below a certain age (e.g., age 16 years in Texas).

Fully informed consent may also be problematic. Practitioners should be aware of pertinent local

regulations governing the age of consent for medical procedures. The APA Committee on ECT

(American Psychiatric Association 2001) calls for a second opinion from a psychiatrist not

otherwise involved in the case, who is experienced in treating children or adolescents (one for

patients ages 13–17 years and two for patients age 12 years and under). Guidelines for the use of

ECT in adolescents have been proposed by the American Academy of Child and Adolescent

Psychiatry (Ghaziuddin et al. 2004a, 2004b).

ECT in Treatment of the Elderly

No one is “too old” for ECT. Risks associated with ECT increase with age, largely because of medical

comorbidity, but they also do so for all viable treatment alternatives, possibly at a higher rate

(Coffey and Kellner 2000; Sackeim 1998). ECT appears to be associated with a lower mortality rate

than otherwise treated elderly patients with severe depressive illness (Philibert et al. 1995). Given

the prevailing risk–benefit considerations and the substantial functional impairment due to

depression in late life, it is not surprising that elderly patients account for a greater fraction of

overall ECT use than they did in the past (34% in 1986 vs. 24% in 1980) (Thompson et al. 1994).

Advanced age does have certain implications regarding ECT technique, since the pharmacological

agents used with the procedure are subject to age-dependent changes in tolerance and metabolism,

and because seizure threshold rises with age.

Evidence for Acute-Phase Efficacy in Major Depression

ECT is the most rapid and effective treatment available for major depressive episodes. The evidence

includes a sizable number of well-controlled “sham-ECT” studies. A meta-analysis, for example

(Janicak et al. 1985), found that ECT was 20% more likely to induce a remission than were tricyclic

antidepressants (P < 0.001), a potent class of antidepressant medications. ECT has been associated

with a remission rate of 80%–90%, with maximum response typically attained after 2–4 weeks, but

the remission rate with ECT varies as a function of certain prognostic factors (see below).

Unfortunately, there have not yet been adequate comparisons between ECT and newer

antidepressant agents or, more importantly, combination treatments.

ECT is as effective in severe nonmelancholic episodes as it is in episodes characterized by

melancholic features (Sackeim and Rush 1995). Similarly, efficacy appears to be equivalent in

depressed patients with unipolar and bipolar mood disorders, though bipolar patients may show a

more rapid response (Daly et al. 2001). Psychotic depression, particularly with mood-congruent

delusions, is associated with an increased likelihood of success of ECT, compared with nonpsychotic

depression (Petrides et al. 1994; Sobin et al. 1996). Primary depressive episodes are more likely to

show full improvement with ECT than are those that are comorbid with dysthymia, anxiety

disorders, and borderline personality disorder (Prudic et al. 2004; Zorumski et al. 1986). In

addition, patients with medication-resistant depression have a lower remission rate with ECT

(Dombrovski et al. 2005; Prudic et al. 1996). Whether this effect is due to more

treatment-refractory cases or to longer depressive episodes in this patient group is unclear.

Unfortunately, such individuals are also less likely to respond to antidepressant interventions of

any type. For this reason, ECT may still be the most effective treatment in at least some such cases.

Evidence for Continuation/Maintenance–Phase Efficacy

For nearly all patients responding to ECT for depression, continuation/maintenance (C/M) therapyPrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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is necessary. C/M therapy usually consists of antidepressant medications, typically continued for at

least 1 year. However, continuation pharmacotherapy may be less effective in patients whose ECT

indication was medication resistance (Sackeim 1994; Sackeim et al. 1990). For these patients,

pharmacotherapy may be combined with C/M ECT (American Psychiatric Association 2001; Petrides

et al. 1994; Rabheru and Persad 1997; Sackeim 1994). Most experts believe that existing data

support the use of C/M ECT when medication refractoriness or intolerance is present in C/M

antidepressant medication trials. However, C/M ECT may still be underutilized.

Specific indications for continuation ECT are 1) history of recurrent episodes responsive to ECT and

either 2) ineffectiveness of or intolerance to prophylactic pharmacotherapy or 3) patient preference

(American Psychiatric Association 2001). In some cases, patients will receive fewer total ECT

treatments had they not received continuation ECT (i.e., these patients thus have fewer relapses,

which often require an entire new course of ECT). Long-term use of C/M ECT is indicated either

when the patient’s history suggests a high risk of delayed relapse on medication alone or when

evidence of decompensation occurs during attempts to stretch out the interval between treatments

during the continuation phase. Average duration of continuation ECT has been reported at 10 weeks

(Petrides et al. 1994) to 6 months (Andrade and Kurinji 2002).

A recently completed randomized study contrasting the utility of continuation ECT alone (no

medications) versus a combination of nortriptyline and lithium failed to find a difference between

the groups (Kellner et al. 2006). However, it can be argued that the ECT arm was weakened by

giving only 10 treatments in 6 months and not allowing any medications. Routine clinical practice

would involve treatment with medications and continuation ECT in combination.

Contraindications and High-Risk Situations

There are no “absolute” contraindications for ECT. The decision to give any treatment is based on

an assessment of risks and benefits among the available treatment options. However, situations do

exist in which the risk of ECT is sufficiently high that its indications should be extremely strong

before considering ECT (American Psychiatric Association 2001).

The presence of a space-occupying intracerebral lesion has traditionally been considered to be just

such a situation, since ECT increases intracerebral pressure. However, recent reports have indicated

that slow-growing meningiomas without mass effect, as well as similar lesions of other types, do

not present a high risk for ECT (Krystal and Coffey 1997) or the risk can be diminished

pharmacologically (Patkar et al. 2000). Recent myocardial infarction may markedly raise risk levels,

due to the effects of ECT on the sympathetic and parasympathetic nervous system (see “Side

Effects,” below). However, the extent of the lesion, degree of healing, and current cardiovascular

status contribute to the specific level of risk that applies in any given case. Other examples of

high-risk conditions are unstable angina, poorly compensated congestive heart failure, severe

valvular cardiac disease, bleeding (or otherwise unstable) vascular aneurysm or malformation,

recent cerebral infarction, severe pulmonary dysfunction, or additional causes of high anesthetic

risk. In many such cases, however, risk levels can be substantially diminished by pharmacologically

altering the body’s physiological response to the induced seizure (American Psychiatric Association

2001; Weiner 2000). ECT has also been safely administered to patients with a history of brain

surgery, deep brain stimulators, cardiac pacemakers, automatic implanted defibrillators, and vagus

nerve stimulators. Appropriate subspecialty consultation is recommended in such situations.

Side Effects

Mortality

The risk of death with ECT is very low: approximately 1 per 10,000 patients (Abrams 2002;

American Psychiatric Association 2001), comparable to the rate expected from a series of brief

anesthetic procedures alone. Most deaths occur in the above-noted high-risk cases. The most

common cause of death with ECT is cardiovascular decompensation; other causes include prolonged

apnea, status epilepticus, and cerebral herniation (e.g., in unrecognized cases of brain tumor).Print: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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Systemic Morbidity

The systemic morbidity associated with ECT is related to the physiological effects of induced

seizures in a setting of general anesthesia and muscular paralysis. Both sympathetic and

parasympathetic discharges typically produce transient benign disturbances in cardiac rate and

rhythm and in blood pressure. These changes can be associated with arrhythmias or cardiac

ischemia, although significant sequelae are rare (Weiner 2000). Such cardiovascular complications

are most likely in patients with severely compromised comorbid cardiac disease. Pharmacological

prophylaxis may be indicated (American Psychiatric Association 2001; Zielinski et al. 1993).

Although prolonged apnea and status epilepticus are rare events, resources to manage their

occurrence should be available. Bone fractures and other musculoskeletal injuries are prevented by

muscular paralysis, whereas injuries to teeth or soft tissues of the mouth are minimized by an oral

protective device (bite block). More common, usually mild systemic side effects include headache,

muscle pain, and nausea (American Psychiatric Association 2001).

Cognitive and Cerebral Morbidity

Cognitive dysfunction

Amnesia is the most commonly discussed side effect of ECT (American Psychiatric Association

2001; Sackeim 1992; Squire 1986). Memory difficulties increase over an index course of treatments

and diminish once ECT is stopped. Less often, memory function may actually improve following ECT,

especially when depression-related cognitive deficits or frank pseudodementia is present. Amnesic

effects with ECT are more prominent and last longer in patients with preexisting cerebral disease,

larger numbers of treatments in a course, or bilateral stimulus electrode placement, particularly

when treatment frequency is maintained at three times weekly.

Two types of memory deficits occur with ECT. More prominent is retrograde amnesia (i.e., difficulty

in remembering information learned before the ECT course). This deficit is greatest for more recent

memories, particularly those occurring within months before the ECT. Retrograde amnesia seems to

be more marked for information of an impersonal nature (Lisanby et al. 2000b). Objective testing

has revealed that these losses diminish over the weeks to months following ECT, except for some

recent memories—particularly those during the ECT treatment period and the preceding months

(American Psychiatric Association 2001; McElhiney et al. 1995). The proportion of patients with

persistent retrograde amnesia using objective testing following ECT is unknown; patient surveys

suggest that this may occur in a sizable minority (Sackeim 1992).

ECT can also induce anterograde amnesia (i.e., difficulty retaining newly learned information), most

severe during the ECT course and typically resolving in days to weeks following ECT

discontinuation.

The likelihood, severity, and persistence of ECT-induced amnesia are influenced by how ECT is

administered, particularly electrode placement and dosing (American Psychiatric Association 2001;

Sackeim et al. 1993, 2000; Sobin et al. 1995; Squire 1986). Severe amnesia during the ECT course

can be managed by increasing the interval between treatments (from three per week to two per

week or even one per week), changing ECT type (e.g., bilateral to unilateral electrode placement),

or, if necessary, ending the treatment course. Pharmacological attempts to ameliorate ECT-induced

amnesia (e.g., by using nootropics, hormones, stimulants, and peptides) have not been reliably

demonstrated (Krueger et al. 1992).

Complaints of more extensive or severe, long-lasting memory deficits have been reported by

patients (American Psychiatric Association 2001; Sackeim 1992). The incidence of these deficits,

while not precisely known, appears to be much lower than the more typical effects described above.

The etiology of these complaints is unclear. Many of these patients perform normally on objective

memory testing (although retrospectively testing for retrograde amnesia is difficult). These

complaints may involve nonphysiological characteristics (e.g., retrograde amnesia without a

temporal gradient) or other etiological factors (e.g., medication effects). Yet psychological factorsPrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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may also play a role (e.g., an increased sensitivity to normal forgetting following a transient

organic amnesic effect, the development of conversion-type syndromes, or secondary gain).

Delirium

A period of postictal confusion, from 10 minutes to more than 1 hour after the seizure, is common.

The occurrence of interictal delirium, however, is far less common and seems most likely in patients

with preexisting cerebral impairment (e.g., Parkinson’s disease) (Krystal and Coffey 1997).

Structural brain changes

Metabolic, neurochemical, and neuropathological evidence indicates that structural brain changes

do not occur with electrically and chemically induced seizures (Coffey et al. 1991; Devanand et al.

1994). Prospective long-term follow-up studies with brain magnetic resonance imaging in humans

have confirmed these findings. Furthermore, there has been no evidence for neuropathological

damage following chronic treatment with bilateral ECT in monkeys (Dwork et al. 2004).

Electroconvulsive Therapy Technique

Informed Consent Process

Informed consent is provided by the patient or by an individual designated under state law (usually

a family member) for patients who are incapable of informed consent. All consent procedures

should follow applicable state regulations (which vary considerably). Consent is an ongoing

process, which can be revoked at any time. Although the consent form covers the entire series of

ECT treatments (except in certain states), it is recommended that reconsent be obtained if an index

series is unusually prolonged. Because C/M ECT differs in a number of ways from an index course of

treatments, it is useful to have a separate consent form for such purposes. Specific information that

should be provided in the consent is provided in the American Psychiatric Association Committee on

ECT 2000 report (American Psychiatric Association 2001).

Lay information on ECT, in both written materials and videotapes, can be obtained from the APA

(i.e., “Fact Sheet” on ECT) and from ECT device manufacturers. Several books oriented to the

general public are available (Endler 1990; Fink 1999). Any major discrepancies between local

regulations and publicly obtained information should be pointed out to the consentee.

Pre-ECT Psychiatric and Medical Workup

Individuals privileged to administer ECT at the facility should evaluate patients before initiating

treatment (American Psychiatric Association 2001). The history and examination should 1)

delineate the indication for ECT; 2) address the nature and effects of prior treatments, including

ECT; 3) assess risk factors based on a medical, anesthetic, and dental history and address how

applicable risks might be reduced; and 4) make recommendations for any further pre-ECT

consultations or laboratory studies (many practitioners routinely screen patients with a complete

blood count, serum potassium and sodium levels, an electrocardiogram, and a pregnancy test for

women of child-bearing potential) or any changes in the patient’s management that are indicated

before or during ECT, including alterations in type and dosage of both psychotropic and medical

pharmacological agents. Furthermore, a preoperative anesthetic assessment by an anesthesia

provider to further clarify risk and to determine whether and how such risks could be minimized,

particularly in terms of modifications of the anesthetic procedure, should be conducted.

Management of Medications Before and During ECT Course

A plan to manage patients’ medication regimens (both psychotropics and other agents) is called for,

including which medications to discontinue and which to be taken before or held until after

treatment on ECT days. Medications that are medically essential or have a protective effect in

regard to ECT (e.g., most cardiac agents and antireflux preparations) should be administered before

ECT on treatment days, keeping fluid intake to a minimum. In general, agents that have a

potentially deleterious effect—either diminishing efficacy of ECT or increasing risk—should bePrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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discontinued or substituted by another agent whenever possible; at the least, dosages should be

decreased to the minimum necessary. Examples of medications that may interfere with the efficacy

and safety of ECT include theophylline, lithium, benzodiazepines, and anticonvulsants (American

Psychiatric Association 2001). Whether ECT increases the risk of cerebral toxicity from lithium is

debated (American Psychiatric Association 2001; Mukherjee 1993; Small and Milstein 1990).

Holding the lithium dose for 24 hours before each ECT treatment may decrease the risk and is

standard practice at some centers. When benzodiazepines cannot be withdrawn, held, or reduced,

the antagonist flumazenil can be used to reverse their anticonvulsant effect during ECT (Krystal et

1. 1998). In such cases, a parenteral benzodiazepine (e.g., intravenous midazolam) should be

administered immediately after the seizure to avoid withdrawal symptoms. Antipsychotic

medication should be continued during ECT in patients with psychosis, particularly those with

schizophrenia or schizoaffective disorder, as the two treatment types may have synergistic action.

Currently, the augmentation of ECT with antidepressant medications is widespread, but only

preliminary data directly address this practice (American Psychiatric Association 2001; Lauritzen et

1. 1996).

ECT in Patients With General Medical Illness

Patients receiving ECT often have concomitant general medical conditions, many of which raise

specific concerns when ECT is used (American Psychiatric Association 2001; Weiner 2000). Patients

with hypertension should have blood pressure stabilized before ECT and receive their routine

antihypertensive medication(s) before each treatment. Patients with coronary artery disease

should also receive their antianginal agents before ECT, and consideration should be given to the

use of acute sympatholytics when ECT is delivered to avoid peri-ECT angina. Cardiac pacemakers

reduce the cardiac risk of pathological arrhythmias with ECT, as do implanted cardiac defibrillators.

However, cardiologist consultation before ECT is still recommended for these individuals. Similarly,

patients who have diabetes mellitus or asthma and those who are pregnant require special

management (Miller 1994; Wisner 1988).

Staffing and Location of ECT Treatments

The provision of ECT requires highly trained and experienced staff. The anesthesia provider also

maintains the patient’s airway and handles medical emergencies (American Psychiatric Association

2001). Separate treatment and recovery areas should be provided whenever possible. Constraints

on clinical practice have increased the pressure to provide ECT on an outpatient basis, but this

should only be done in cases where the patient does not require hospitalization and can comply

with the treatment regimen (American Psychiatric Association 2001; Fink et al. 1996). Such

patients should be briefly evaluated before each treatment and not discharged until he or she is

capable of leaving with the assistance of a significant other.

Number and Frequency of Treatments

The number of ECT treatments administered in an index course is based on clinical progress (see

“Continuation/Maintenance Therapy” section for treatment number and frequency with that

modality). Typically, patients require 6–12 treatments in an index course, although as few as 3 or

greater than 20 may be required. As noted, reconsent should be considered when an unusually long

course is required (American Psychiatric Association 2001). There does not appear to be any

benefit in continuing ECT once a therapeutic plateau (i.e., no further improvement) is reached. In

cases of partial improvement, consideration should be given to optimize technique (see

“Management of Missed, Inadequate, or Prolonged Seizures,” later in chapter). There is no “lifetime

maximum” number of treatments.

In the United States, ECT is usually administered three times a week (American Psychiatric

Association 2001). Some recent studies indicate that administration of twice-weekly bilateral ECT

treatments (as performed elsewhere) results in a therapeutic response similar to that with

thrice-weekly treatments but with fewer short-term cognitive side effects, although response rate

is slower (Shapira et al. 1998). Patients with an urgent need for rapid response may be treatedPrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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daily for the first few treatments, whereas patients who develop delirium or severe cognitive

deficits may require a reduction in treatment frequency. Multiple monitored ECT (induction of

multiple seizures in a single treatment session [Maletzky 1981]) increases risks of cognitive

deficits, prolonged seizures, and exaggerated cardiovascular response (Abrams 1997). It is no

longer within the standard of practice, with the exception of double-seizure induction for dosage

titration (see “Stimulus Dosing,” later in chapter) at the initial ECT treatment.

Anesthetic Issues

Anticholinergic Agents

Anticholinergic agents are used to minimize oropharyngeal secretions and the risk of posttreatment

asystole or bradycardia. Glycopyrrolate is the agent preferred by many practitioners because it is

less likely to cross the blood-brain barrier and thus potentially exacerbate cognitive side effects.

Anticholinergic premedication is most important for cardiac patients and with use of subconvulsive

stimulations (American Psychiatric Association 2001).

Sympatholytic Agents

The transient surge in systolic pressure and heart rate following seizure onset is of concern in

patients at risk for cardiac ischemia. The effect can be attenuated, but hypotension should be

avoided. Careful agent selection includes consideration of duration of action and anticonvulsant

effects.

Ventilation

The airway should be ensured and oxygen ventilation begun before infusion of muscle relaxant and

anesthetic, and ventilation should be continued until the patient resumes spontaneous breathing

(except during electrical stimulus delivery) (American Psychiatric Association 2001). A flexible

mouth guard protects the patient from the involuntary muscle contractions that accompany the

electrical stimulus.

Anesthesia

A light level of anesthesia is used to provide amnesia for the effects of the muscular paralysis and

the electrical stimulation with minimal interference with seizure induction. The primary agent used

in the U.S. is methohexital, a rapidly acting barbiturate with a short half-life (American Psychiatric

Association 2001; Swartz 1993). Propofol has been avoided because of its even greater

anticonvulsant properties (Swartz 1992), although this effect has not been associated with

diminished efficacy (Martensson et al. 1994). Ketamine, which does not raise seizure threshold, is

an alternative agent for patients with very high seizure thresholds (Rasmussen et al. 1996), as is

etomidate, which can lengthen seizures (Avramov et al. 1995; Gazdag et al. 2004).

Muscular Relaxation and Physiological Monitoring

Because of its rapid action and extremely short half-life, succinylcholine is the muscle relaxant of

choice for ECT. Alternative agents include the muscarinic antagonists, which are associated with a

longer period of apnea. Current monitoring includes respiration, carbon dioxide, blood oxygen

saturation, blood pressure, and heart rate from before anesthesia induction until the time the

patient leaves the treatment room.

Stimulus Electrode Placement

For many years, ECT stimulus electrodes were applied bitemporally—so-called bilateral (BL) ECT.

Nondominant (and hence generally right) unilateral (RUL) ECT places both electrodes over the

nondominant cerebral hemisphere, thereby relatively sparing verbal memory function (Lancaster et

1. 1958).

Dozens of additional investigations comparing the efficacy and safety of various forms of RUL

versus more traditional BL ECT (reviewed in Abrams 2002) have demonstrated 1) less frequent,Print: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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severe, and persistent memory impairment, particularly in regard to left-hemisphere function, with

RUL ECT; and 2) a more rapid or pronounced antidepressant effect with BL ECT. RUL ECT

administered using a frontotemporal to high-centroparietal configuration (d’Elia 1970) in

combination with a significantly suprathreshold stimulus intensity (see “Stimulus Dosing,” below)

improves efficacy, although it is not necessarily equivalent to BL ECT (McCall et al. 2000; Sackeim

et al. 1993, 2000). The increases in RUL ECT stimulus intensity are associated with increased

amnesia, although less than is seen with BL ECT. Bifrontal electrode placement has also shown

evidence of improved cognitive outcome relative to BL. However, more evidence is needed

comparing bifrontal ECT with suprathreshold RUL ECT (Bailine et al. 2000; Ranjkesh et al. 2005).

Thus, electrode placement and stimulus intensity are made on a case-by-case analysis of

anticipated benefits versus likely risks (American Psychiatric Association 2001).

Electrical Stimulus

Electrical Principles Pertinent to ECT

The electrical stimulus is applied once maximal muscular paralysis has been attained and good

electrical continuity (i.e., low interelectrode impedance) is established. Contemporary ECT devices

made in the U.S. allow monitoring of this electrical continuity.

At present, ECT devices are produced by two companies in the U.S.: MECTA, Inc. (Lake Oswego,

OR), and Somatics, Inc. (Lake Bluff, IL). In both cases, the signal used for the ECT stimulus is the

bidirectional brief pulse. Sine wave stimuli delivered by older devices are no longer recommended.

Brief pulse ECT is characterized by pulse width (e.g., 0.25–2.0 msec), pulse frequency (e.g., 40–90

Hz, or pulse pairs per second), duration of the entire train of pulses (e.g., 0.5–8.0 seconds), and the

peak current of each pulse (e.g., 0.5–1.0 amp). The use of very narrow pulses (e.g., 0.25–0.5 msec)

is termed ultra-brief pulse ECT and may offer a further potential for stimulus optimization. A single

composite stimulus intensity parameter is the charge (in millicoulombs).

Stimulus Dosing

The seizure threshold is the minimum stimulus intensity required to induce a generalized seizure. It

varies as much as 50-fold across patients. Seizure threshold is higher in men and in older persons,

and it increases with more ECT treatments. Seizure threshold is lower with RUL d’Elia placement

(American Psychiatric Association 2001; Sackeim et al. 1991). Also for RUL ECT, efficacy increases

as a function of how much the stimulus intensity exceeds the seizure threshold. RUL ECT at 500%

above threshold approaches the efficacy of BL ECT (Sackeim et al. 1993, 2000).

Based on these relationships, the most precise method for stimulus dosing is to determine the

seizure threshold with a titration procedure at the first treatment and to then administer a stimulus

at a chosen degree above threshold subsequently. Various dosing schedules have been suggested

to individualize ECT delivery (Coffey et al. 1995). Fixed formula dosing techniques are available, but

less accurate (American Psychiatric Association 2001).

Seizure Monitoring

Monitoring of Motor Response

Visual seizure monitoring of the motor convulsive response (Weiner et al. 1991) has been used to

detect the presence and duration of the motor convulsive response. A blood pressure cuff inflated

to above the systolic pressure and placed on the hand or foot before infusion of the paralytic agent

is used. When RUL ECT is given, cuffing the right ankle is recommended to help ensure that the

seizure is bilateral.

Monitoring of Electroencephalographic Response

ECT-induced seizures involve the intense and highly synchronous discharge of neurons throughout

the cerebral hemispheres, which are best monitored by scalp-recorded electroencephalography

(EEG) (American Psychiatric Association 2001; Weiner et al. 1991). The EEG seizure typically lastsPrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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10–15 seconds longer than the ictal motor response. In some individuals, prolonged EEG seizures

occur that are not detected by motor response monitoring. Therefore, single- or double-channel EEG

monitoring is recommended. Double-channel monitoring (available on most U.S. ECT devices) is

recommended to observe seizure symmetry and to provide backup when substantial EEG artifacts

occur. The EEG seizure typically begins by the end of the stimulus. The tonic portion of the ictal

motor response is usually characterized by a polyspike format, whereas the clonic portion shows a

polyspike–slow-wave pattern. The end of the seizure may be abrupt or gradual, and the immediate

postictal EEG is suppressed and may appear “flat” (Krystal et al. 1993; Nobler et al. 1993).

Determination of Seizure Adequacy

Historically, seizure duration was assumed to be the primary measure of seizure adequacy, with a

typical clinical cutoff criterion of 25 seconds (Weiner et al. 1991). However, work by Sackeim et al.

1993) showed that for RUL ECT, seizure duration did not ensure the therapeutic efficacy of ECT as

well as increase in stimulus intensity. Alternative EEG-based measures sensitive to the extent to

which the stimulus is suprathreshold would better guide the determination of the lowest effective

stimulus intensity to maximize efficacy while keeping side effects to a minimum (Krystal et al.

1998). Some studies suggest that amplitude and regularity of ictal EEG slow waves and the degree

of postictal EEG suppression have promise in this regard (Krystal et al. 1998). However, no

EEG-based models have yet been validated for use in clinical dosing.

Management of Missed, Inadequate, or Prolonged Seizures

Missed seizures lack therapeutic effects. They should be followed by increasing the stimulus

intensity (e.g., 50%) after an interval of approximately 20 seconds (to rule out delayed ictal

response). Brief (abortive) or otherwise inadequate seizures should be followed by restimulation at

a higher stimulus intensity after 45 seconds to allow the relative refractory period to pass. If the

patient’s seizure threshold exceeds the capability of the ECT device, the threshold can be decreased

by lowering the dose of anesthetic agent (if possible), by switching to etomidate or ketamine

for anesthesia, or by stopping/decreasing concurrent medications with anticonvulsant properties

(American Psychiatric Association 2001). Prolonged seizures (i.e., lasting longer than 3 minutes)

should be terminated pharmacologically (American Psychiatric Association 2001). Poorly

suppressed postictal EEG or inappropriately high EEG amplification can be misinterpreted as a

prolonged seizure.

Continuation/Maintenance Therapy

Maintenance Pharmacotherapy

Most individuals who receive ECT have a chronic or recurrent prior course of illness that puts them

at risk for recurrence—particularly during the first 6 months after remission (American Psychiatric

Association 2001). The 1-year recurrence rate following ECT is 50% despite medications (Sackeim

1994; Sackeim et al. 1990). Thus, continuation therapy is essential (American Psychiatric

Association 2001). For most cases, psychotropic medications are used. However, patients with a

history of medication resistance during the index episode are less likely to maintain remission on

continuation pharmacotherapy than nonresistant patients (Sackeim et al. 1990). For

medication-resistant patients who respond to ECT, consider giving the patient either a class of

medication not previously used or continuation ECT (American Psychiatric Association 2001;

Sackeim 1994).

Continuation ECT

When continuation-phase medications do not maintain remission, C/M ECT should be considered.

Continuation ECT following successful ECT typically involves gradually shifting from frequent (e.g.,

weekly) to monthly treatments over 1–3 months and then maintaining the monthly administration

schedule for at least 6 months after remission (or longer if indicated) (American Psychiatric

Association 2001; Fink et al. 1996). Decisions regarding scheduling should be made on an ongoing

basis, based on the patient’s history and present response. Concomitant psychotropic agents mayPrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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be useful for patients who are unable to benefit fully with continuation C/M ECT alone. Although

C/M ECT may slow the resolution of the index ECT course–associated memory disturbance, the

development or worsening of memory impairment is thought to be unlikely unless there is

prolonged use of short-interval C/M ECT (weekly or bimonthly), though some patients tolerate it

well. The need for C/M ECT should be reviewed by the practitioner and patient at least twice a year;

consent should be reobtained at least every 6 months, as should anesthetic/medical and cognitive

reevaluations. The presence of persistent memory deficits should be weighed against the

anticipated benefits of continuing ECT.

Case Examples

Case 1

Mr. B, a 72-year-old right-handed man, was being treated for a major depressive episode. He was

transferred from the inpatient service of a freestanding psychiatric hospital because of serious medical

comorbidity (severe coronary artery disease) and deterioration in his overall condition. Mr. B had been

well until 3 months before admission. At the time of his transfer, his psychiatric presentation was

characterized by intense dysphoria, inability or unwillingness to answer questions, severe motor

retardation, a belief that he had committed terrible deeds and should be punished, and refusal to eat.

Although he had been hospitalized in the initial facility for a week, antidepressant medications had not

been initiated because of the staff’s concern about his medical condition. Medically, Mr. B’s coronary

artery disease was characterized by angina on exertion, requiring daily antianginal medication, and a

cardiac ejection fraction of 30% (indicating a severe level of dysfunction). The preliminary diagnosis was

major depression with psychotic features.

Because of the gravity of Mr. B’s presentation, a referral for ECT on a primary basis was indicated.

Although a cardiology consultation corroborated the level of cardiac dysfunction, the consultant also

agreed that Mr. B’s mental condition represented an even greater risk than proceeding with ECT. Mr. B

was not able to follow a discussion on ECT by the attending psychiatrist and indicated that he did not

want treatment or food because he deserved to die. Because he did not have the capacity for providing

informed consent, a guardianship procedure was begun and his son was adjudicated the appointed

guardian and provided surrogate consent.

Mr. B received his routine oral antianginal agent 2 hours before ECT and was further premedicated with

intravenous labetalol 5 mg, given 2 minutes before anesthesia induction. Because of the urgent need for

a rapid response, he was administered BL ECT at a rate of three treatments per week. Mr. B tolerated the

procedure well, except for some transient premature ventricular contractions lasting 2 minutes

postictally. These contractions were prevented in successive treatments by an increase in the labetalol

dose. After three treatments, a clear improvement in his symptoms was noted, along with some

confusion occurring between treatments. Decreasing the rate of treatments to two per week allowed

continued improvement with only mild levels of confusion and amnesia. After six treatments Mr. B was

back to his premorbid state. His son described the patient’s response as “being brought back from the

dead.” Mr. B was given nortriptyline on discharge from the hospital. He remained well at 1-year

follow-up.

Case 2

Ms. C was a 58-year-old right-handed woman with a long history of recurrent major depression. After

numerous unsuccessful trials of various antidepressant medications, both alone and in combination, her

prior 3 episodes had led to referrals for BL ECT. These courses of treatment were associated with a

marked improvement and were well tolerated except that she experienced moderate transient memory

impairment. After each course of ECT, the last of which ended 5 months previously, she was given

continuation pharmacotherapy, with only transient benefit. No medical risks were present on pre-ECT

evaluation during the last 3 episodes.

Because of her recent history of good response, except for memory disturbance with prior ECT, Ms. C was

referred for a course of RUL ECT treatments to reduce the risk of cumulative cognitive morbidity.Print: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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However, little therapeutic response was evident after the sixth treatment, in contrast to what had been

observed during her previous BL ECT courses. Following discussion with Ms. C and her husband, she was

switched to BL ECT and began to show improvement after two further treatments. During the tenth

treatment it was noted that Ms. C’s EEG seizure duration had fallen to 22 seconds, despite the use of

maximum electrical stimulation. Beginning at the eleventh treatment, her anesthetic agent was switched

from methohexital to ketamine, leading to a 100% increase in seizure duration. Ms. C continued to

improve and reached a therapeutic plateau after 13 treatments.

Because of her history of rapid relapse, Ms. C was referred for C/M ECT, for which she provided informed

consent. Treatments were begun at the rate of one per week for 4 weeks, followed by one every 2 weeks

for an additional 4 weeks, one per 3 weeks for the next 6 weeks, and then monthly. Throughout this

period, Ms. C remained in clinical remission without adverse effects. After 12 months on C/M ECT, the

treatments were stopped, with close follow-up maintained. At her most recent visit, 18 months following

the most recent index course, Ms. C was still taking no psychotropic medications, and she continued to

be euthymic.

VAGUS NERVE STIMULATION

Vagus nerve stimulation (VNS) is FDA approved for adjunctive treatment of chronic or recurrent

medication-resistant depressive episodes in adults, and it is also approved for treatment-refractory

partial-onset seizures. VNS entails the direct, intermittent electrical stimulation of the left cervical

vagus nerve via a pulse generator implanted in the left chest wall. The electrode is wrapped around

the left vagus nerve in the neck and is connected to the generator subcutaneously. Intermittent left

VNS sends afferent signals to the nucleus tractus solitarius and connected limbic and cortical areas

(George et al. 2000). Implantation surgery involves two incisions: one in the chest for the

generator, and another in the neck for the electrode. Surgery is usually performed under brief

general anesthesia, as day surgery or with an overnight stay. Stimulation parameters are adjusted

with a programming wand that communicates with the generator. Patients may turn off the

stimulation when needed by holding a magnet over the generator.

In the first study of 30 treatment-resistant depressed patients (Rush et al. 2000), response rates

were 40% after 10 weeks of open-label, adjunctive VNS treatment. The response rate was

sustained (46%), and the remission rate significantly increased (from 17% to 29%) after an

additional 9 months of VNS treatment (Rush et al. 2005b); in addition, substantial improvements in

function were reported with long-term VNS therapy.

In a subsequent report of an extended sample (n = 59) (Sackeim et al. 2001b), the short-term (3

months) and longer-term (24 months) effects of adjunctive VNS treatment (Nahas et al. 2005)

revealed 10-week response rates of 31% (after 3 months), 44% (after 1 year), and 42% (after 2

years). Remission rates were 15%, 27%, and 22% respectively, demonstrating continuous and

stable improvement. By 2 years, 81% were still receiving VNS.

However, a 10-week randomized, controlled, masked multicenter trial comparing adjunctive VNS

with sham treatment in 235 outpatients with treatment-resistant unipolar or bipolar depression

failed to show a significant difference on the primary outcomes between active and sham treatment

(Rush et al. 2005a). However, a naturalistic follow-up study of long-term (1-year) VNS treatment of

the same cohort (n = 202) revealed progressively increasing improvement, with a 12-month

response rate of 27.2% and a remission rate of 15.8%. These results, compared with those seen in

a comparably matched but nonrandomized control group that received treatment as usual,

indicated that VNS was associated with greater improvement than pharmacological treatment alone

(27% vs. 13%) (George et al. 2005). The finding of significant longer-term benefit of adjunctive

VNS relative to active treatment excluding VNS was from an open-label study in which treatment

was not controlled. On the other hand, the improvement in VNS patients was not attributable to

medication changes, nor was a delayed placebo effect likely in such chronically ill

treatment-resistant patients.

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VNS is generally well tolerated. Voice alteration, dyspnea, and neck pain are the most frequently

reported adverse events (George et al. 2005). The surgical implantation does carry the risks of

infection, vocal cord paralysis, and bradycardia or asystole (single occurrences for all, except no

vocal cord paralysis in the randomized controlled trial [Rush et al. 2005a]). In the long-term

naturalistic study of VNS for major depression, only 3 out of 235 patients (1%) terminated VNS

because of adverse events (George et al. 2005). VNS does not cause cognitive side effects (Sackeim

et al. 2001a). In fact, neurocognitive performance was significantly improved with VNS—apparently

due to the improvement in depression (Sackeim et al. 2001a).

Indications and Contraindications for VNS

VNS is approved as an adjunctive long-term treatment for chronic or recurrent depressive episodes

in adults with a major depressive episode who have not had an adequate response to four or more

adequate antidepressant trials. Determination of what constitutes an adequate trial requires careful

assessment of whether adequate dosages were prescribed (and taken) for an adequate period of

time. Optimally, this should be substantiated by careful review of treatment records, pharmacy

reports, and blood levels where appropriate. Trials should have included different medication

classes (i.e., not just selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake

inhibitors but also tricyclic antidepressants and monoamine oxidase inhibitors) or various

augmentation strategies with or without ECT. A second opinion from a clinician specializing in

treatment-resistant depression and knowledgeable regarding VNS is advisable.

VNS is contraindicated in patients with bilateral or left cervical vagotomy, and patients with a VNS

implant should not receive short-wave diathermy, microwave diathermy, or therapeutic ultrasound

diathermy. The efficacy of VNS in other disorders is unknown.

VNS does not exert rapid antidepressant action. Acutely suicidal patients and others in need of

rapid response would be more appropriately treated with other strategies. VNS is indicated as a

long-term treatment option only for those with a chronic or recurrent course of illness.

ECT can be safely used in patients with an implant if the VNS generator is turned off during delivery

of ECT to avoid anticonvulsant effects of VNS. Whether VNS would be useful in relapse prevention

post-ECT deserves study.

VNS Dosing

The optimal dose of VNS is unknown. The published studies were not designed to identify optimal

dosing parameters (time on, time off, frequency, current, pulse width). The epilepsy literature

suggests that there is a threshold current for efficacy. However, because that threshold is unknown

for VNS, current is typically increased up to >1 milliamperes (mA) and clinical benefit assessed

over several months. The side effects of VNS are known to be dose dependent (e.g., lowering pulse

width reduces neck pain, allowing patients to tolerate higher currents).

TRANSCRANIAL MAGNETIC STIMULATION

Transcranial magnetic stimulation (TMS) provides noninvasive brain stimulation with time-varying

magnetic fields to induce electrical current and neuronal depolarization in targeted cortical regions

(Barker et al. 1985). Repetitive TMS (rTMS) pulses are delivered at 1–20 Hz. Low-frequency ( 1 Hz)

rTMS reportedly decreases neuronal excitability, while high-frequency (10–20 Hz) rTMS increases it

(Speer et al. 2000). Unlike ECT, rTMS requires neither anesthesia nor seizure induction. rTMS does

not produce disorientation or clinically apparent cognitive side effects. rTMS sessions typically last

30 minutes and are repeated daily, 5 days per week, with the length of treatment ranging from 2 to

4 weeks. The few studies of longer acute treatment for depression revealed continued improvement

over the third and fourth weeks (Rumi et al. 2005). Although optimal dosing has not been fully

examined, studies generally suggest that higher intensities, more pulses per session, and more

pulses per course are associated with superior outcome (Gershon et al. 2003).

During rTMS, patients are awake and require no anesthesia. Other than headache and scalp pain,

there are no significant common side effects; thus, outpatients return to work or otherPrint: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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responsibilities immediately following each treatment session. rTMS carries a risk of seizure when

excessively high levels of stimulation are used. The intensity of the magnetic stimulus is measured

as a percentage of the motor threshold, the minimum intensity required to elicit a twitch in a target

hand muscle in 5 of 10 trials. Most treatment trials have used intensities between 80% and 120%

of the motor threshold. Careful attention to published safety guidelines regarding dosage selection

and medical monitoring is important to ensure safety (Belmaker et al. 2003; Wassermann 1998).

The FDA has labeled TMS devices “to be used by prescription only,” which means under the

direction of a physician. TMS must be given by clinically trained personnel supervised by a

physician.

The potential research and clinical use of TMS have been reviewed elsewhere (George et al. 1999;

Lisanby et al. 2002; Wassermann and Lisanby 2001). TMS is not currently FDA approved for any

clinical condition, although it is approved as a treatment for depression in Canada. Most of the

clinical work with TMS has focused on its potential therapeutic value in the treatment of

depression, but promising work is emerging in schizophrenia and anxiety disorders.

A growing number of studies suggest that rTMS may be useful in the treatment of major depressive

episodes (Aarre et al. 2003; Burt et al. 2002; Holtzheimer et al. 2001; Kozel and George 2002; Loo

and Mitchell 2005). The antidepressant efficacy of rTMS appears comparable to that of ECT in

nonpsychotic patients (Schreiber et al. 2002), but true double-blinding of such comparisons

remains evasive. Most rTMS studies have enrolled patients who are resistant to one or more classes

of antidepressants but not necessarily resistant to ECT. Despite many placebo-controlled trials

revealing a statistically significant difference between rTMS and sham treatment, only a few studies

have reported substantial rates of response or remission. Meta-analyses have reported relatively

low response rates for rTMS (>50% reduction in depressive symptoms; e.g., 13.7% with rTMS vs.

7.9% with sham stimulation [Holtzheimer et al. 2001]) (see also Burt et al. 2002; Kozel and George

2002). Findings from more recent studies using longer durations of treatment and sequential

bilateral stimulation are more encouraging (Fitzgerald et al. 2006; Gershon et al. 2003; Holtzheimer

et al. 2001). Recently released results of a major pivotal trial demonstrated a significant

improvement in the active rTMS group over sham treatment (Aaronson et al., in press).

MAGNETIC SEIZURE THERAPY

Magnetic seizure therapy (MST), a novel investigational treatment, uses high-dose rTMS to induce

seizures for therapeutic purposes (Kosel et al. 2003; Lisanby et al. 2001, 2003a). MST requires

anesthesia but offers better control over the site of stimulation and intracerebral current density

than does ECT. MST allows the targeting of specific brain regions implicated in depression while

reducing the spread to other brain areas. By limiting the spread of activation to limbic regions, MST

may reduce the cognitive side effects associated with ECT. In humans (Kosel et al. 2003; Lisanby et

1. 2003a) and other primates (Moscrip et al. 2005), MST has fewer cognitive side effects than does

ECT.

Since the first use of MST in a patient with treatment-resistant major depression (Lisanby et al.

2001), several trials of MST have been conducted, including a randomized, within-subject,

double-masked trial comparing ECT and MST in 10 patients with treatment-refractory major

depression (Lisanby et al. 2003a). MST seizures had shorter duration, lower ictal EEG amplitude,

less postictal suppression, and faster orientation recovery. Measures of attention, retrograde

amnesia, and category fluency were superior in MST, and fewer subjective side effects were

reported in MST recipients. Because MST has the potential of retaining the efficacy of ECT but with

fewer cognitive side effects, it may be of use for patients who are unresponsive to antidepressant

medications but cannot tolerate ECT.

DEEP BRAIN STIMULATION

With deep brain stimulation (DBS), intracranial electrodes are implanted and chronically stimulate

targeted brain areas. Unlike lesioning procedures, DBS is believed to be fully reversible, and the

intensity of stimulation can be adjusted according to the acute effect on symptoms. DBS has been

successfully used in treatment-refractory patients with Parkinson’s disease, essential tremor,Print: Chapter 27. Convulsive and Other Somatic Therapies http://www.psychiatryonline.com/popup.aspx?aID=257457&print=yes…

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dystonia, and other movement disorders. DBS is being studied for treatment of psychiatric

conditions, such as obsessive-compulsive disorder and depression (Kopell et al. 2004). At this time,

about 20 patients worldwide have received DBS for depressive disorders, with varying stimulation

sites: the white matter underlying cingulate area 25 (Mayberg et al. 2005), the internal

capsule/nucleus accumbens (T. Schlaepfer, personal communication, May 2006), and the inferior

thalamic peduncle (Jimenez et al. 2005).

An open-label series of six patients with treatment-refractory depression were treated with DBS

and demonstrated very encouraging results (Mayberg et al. 2005). Upon activation of DBS, all six

patients spontaneously reported immediate improvement in mood, a feeling of calm, and increased

interests. In four of six patients, antidepressant response was maintained at 6 months, and three of

these four subjects achieved full remission. Subsequent controlled studies are needed to establish

the safety and efficacy of this most focal, although most invasive, treatment for refractory

depression.

TRANSCRANIAL DIRECT CURRENT STIMULATION

Transcranial direct current stimulation (tDCS), or direct current polarization, is a noninvasive

means of electrically polarizing neurons in the human cerebral cortex. tDCS entails the delivery of

1–3 mA of direct current through scalp electrodes, exerting a polarity-dependent effect on cortical

neurons at the stimulation site locally and downstream. Anodal stimulation facilitates cortical

function, while cathodal stimulation inhibits it. tDCS may enhance verbal fluency, improve word

recall, and facilitate recovery from hand paresis in stroke patients (Hummel et al. 2005). A recent

double-blind, randomized, sham-controlled trial of tDCS in depression found significant

antidepressant effect after anodal stimulation over the dorsolateral prefrontal cortex given for

20 minutes per day over 5 alternate days (Fregni et al. 2005). The low cost and good safety profile

of tDCS make it an attractive modality relative to other more invasive and costly procedures

(Nitsche 2002). Further clinical trials of longer duration are indicated.

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