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Electroconvulsive Therapy in Late-Life Depression
Electroconvulsive Therapy in Late-Life Depression
Electroconvulsive Therapy in
Late-Life Depression
depressant medications are too risky, have macologic treatment, duration of the de-
proven ineffective, or when ensuring a pressive episode consistently correlates
rapid or full clinical response is particu- with a positive ECT response: patients (of
larly important. all ages) with longer duration of illness
respond less well.18–24 This relation be-
tween duration of illness and treatment
Indications for ECT response may reflect the impact of depres-
ECT is indicated for the acute treatment sion in CNS functioning. Duration of a
of depression as well as for maintenance depressed state correlates with the extent
treatment and prevention of relapse. Clin- of hippocampal atrophy associated with
ical outcome of ECT is more predictable chronic depression. Because the hippo-
in patients exhibiting particular charac- campus has an established role in regulat-
teristics of major depression. As with phar- ing the hypothalamic–pituitary—adrenal
(HPA) axis, the atrophic effects of depres- Studies comparing ECT to other forms
sion may lead to increased vulnerability of antidepressant treatment15,40 are rela-
to stress and prolongation of the episode. tively sparse. A metaanalysis of early com-
Patients with hippocampal atrophy are parative-age patient samples11 reports
especially resistant to antidepressant that the average response rate to ECT is
medications, particularly tricyclics. Poor 20% higher when compared to tricyclic
response to antidepressants, in turn, antidepressants (TCAs) and 45% higher
predicts/correlates with inferior short- when compared to monoamine oxidase
term response to ECT18,25–27 as well as to inhibitors (MAOIs), although by modern
other somatic treatments.28,29 ECT is standards, the pharmacologic treatments
likely to be of greatest value when it is ad- used were often suboptimal.18,33,41,42 No
ministered early in the course of a depres- study has ever found a pharmacologic reg-
sive episode and not as a last resort after imen to be superior in antidepressant ef-
all other treatments have failed. fects when compared to ECT. Rather,
Maintenance ECT, with treatments ECT consistently has had either equal or
spaced over weekly to monthly intervals, superior efficacy. In both young and el-
is increasingly used for relapse preven- derly populations, ECT is superior to a
tion.30–32 Unfortunately, continuation or standard antidepressant,15 although the
maintenance ECT is commonly employed addition of lithium to an antidepressant
only after pharmacologic methods of re- results in more rapid onset of improve-
lapse prevention have failed following suc- ment compared to ECT in patients with
cessful ECT. At present, the vast majority treatment-resistant depression.40,43,44
of patients who respond to ECT are then Other differences between ECT and
treated with antidepressant medications antidepressant treatments concern speed
despite evidence that failed medication and quality of clinical response as well as
regimens during the acute depressive epi- residual symptoms. Residual symptom-
sode are ineffective in preventing relapse atology resulting from incomplete re-
following ECT.24,26,30,33,34 sponse to antidepressant medications may
become chronic or lead to relapse.45 Be-
cause remission is more likely following
Efficacy ECT, there is less chance of recurrence of
chronic residual depressive symptoms.
Overall, research observations and clini- Whether ECT reduces depressive
cal experience indicate that ECT is partic- symptoms more quickly than antidepres-
ularly useful in the treatment of late-life sants in the elderly has not been ade-
depression. Prior to the introduction of quately tested. Nonetheless, evidence sug-
ECT, elderly depressed individuals often gests that no pharmacologic strategy
exhibited chronic depression or died of results in as rapid symptomatic improve-
intercurrent medical illnesses in psychiat- ment as ECT.10,12,13 Significant clinical
ric institutions.35 A number of studies con- improvement is usually seen within the
trast the clinical outcome of depressed pa- first few treatments, with maximal gains
tients who received inadequate or no seen by 3 weeks. This rapid improvement
somatic treatment to that of patients who is less common with antidepressant medi-
received ECT (Figure 3) While none of cations.
this work involves prospective, random-as-
signment designs, the findings are largely Aging and Efficacy
uniform. Contemporary ECT adminis-
tered to elderly patients results in de- The response rate to ECT is higher among
creased chronicity, decreased morbidity, older patients,46–49 and a positive associa-
and possible decreased rates of mor- tion is seen between patient age and de-
tality.36–39 gree of clinical improvement following
388 Part IV / Affective Disorders
Figure 13.3. Examples of waveforms used in ECT. Top left: sine wave. Top right: chopped, recti-
fied sine wave. Bottom left: brief pulse, square wave. Bottom right: ultra-brief pulse, square wave.
(From Sackeim HA, Long J, Luber B, et al. Physical properties and quantification of the ECT
stimulus: I. Basic principles. Convuls Ther 1994;10:93–123).
ECT.46–49 Table 13.1 provides a selective The extent to which the intensity of the
summary of studies addressing the rela- electroconvulsive stimulus exceeds the in-
tion between patient age and ECT out- dividual patient’s seizure threshold deter-
come. Older individuals, however, may mines the efficacy of right unilateral ECT
have a diminished response to unilateral, and speed of response regardless of elec-
as opposed to bilateral, ECT50,51 and may trode placement.58–62 Age is one of the
require longer courses of treatment to more reliable predictors of seizure thresh-
achieve the same level of remission as old62–64: the oldest patients generally have
younger patients.52,53 ECT may also be ef- the highest thresholds, shortest seizure
fective in the very oldest depressed pa- duration, and lowest EEG seizure ampli-
tients.54–57 tude.60,65,66
In addition to stimulus intensity, evi-
Predictors of Response
dence shows that among depressed pa-
Two factors correlate with response to tients, those with psychotic or delusional
ECT in the elderly: intensity of the electri- depression respond especially well to
cal stimulus, and the patient’s diagnosis. ECT.25,30,67–72 Although not definitively
Table 13.1. Relation Between Patient Age and ECT Outcome: Selected Studies
Prudic et al. 347 patients with major Prospective, naturalistic study of Modified ECT given 3 times/week; Age, treated as a continuous variable,
(2004) depression treated at 7 ECT practices and outcomes in diverse electrode placement and not related to symptom improvement
hospitals in the New York community settings; evaluations dosing practices or categorical clinical outcomes
metropolitan area before, immediately after, and
monthly for 6 months
following ECT
O’Connor 253 patients with major Prospective naturalistic acute Modified ECT given 3 times/week; Lower remission (70%) in youngest age
et al. depression, treated openly phase study followed by double- patients titrated at first session group than either older adults
(2001) with titrated (50% above blind continuation trial and treated afterward with (89.8%) or elderly (90%); when
seizure threshold) comparing nortriptyhline and suprathreshold intensity 50% these dimensions were treated as
bilateral ECT lithium with continuation ECT; above threshold continuous variables, age was also
acute response to ECT related to outcome.
contrasted in 3 patient groups:
young adult (!45 years), older
adult (46 to 64 years) and
elderly (65 years and older)
Sackeim et al. 80 inpatients with major Double-blind, prospective study Modified ECT given 3 times/week; High dosage right unilateral ECT
(2000) depression randomized of effects of electrical dosage patients randomized to 3 forms (6 " threshold) and bilateral ECT
to 4 groups (right and electrode placement; of right unilateral ECT (1.5, 2.5, (2.5 " threshold) equal in efficacy
unilateral at 1.5, 2.5, or patients evaluated before ECT or 6 " seizure threshold) or and superior to lower dosage right
6 times seizure and regularly during and after bilateral ECT (2.5 " ST) unilateral ECT; no age-related effects
threshold or bilateral treatment course
ECT at 2.5 times seizure
threshold); free of all
medications except
lorazepam (up to 3
Chapter 13 / Electroconvulsive Therapy in Late-Life Depression
mg/day PRN)
(continued)
389
390
Tew et al. 268 patients with major Prospective naturalistic acute phase Modified ECT given 3 times/week; More physical illness and cognitive
(1999) depression, treated openly study followed by double-blind patients titrated at first session impairment in both older age groups
with suprathreshold continuation pharmacotherapy and treated with suprathreshold than in adult group. Both older
unilateral or bilateral ECT; trial; acute response to ECT intensity selected by treating groups had shorter depressive
free of all medications contrasted in 3 patient groups: psychiatrist episodes and were less likely to be
Part IV / Affective Disorders
except lorazepam adult (59 years and younger), medication resistant. The adult
(up to 3 mg/day PRN) young-old (60 to 74 years) and patients had a lower rate of ECT
old-old (75 years and older) response (54%) than the young-old
patients (73%), while the old- old
patients had an intermediate rate of
response (67%).
Sackeim et al. 96 inpatients with major Double-blind, prospective study of Modified ECT given 3 times/week; Electrical dosage determined unilateral
(1993) depression randomized effects of electrical dosage and patients titrated at first session ECT efficacy and speed of response
to 4 groups (unilateral or electrode placement; patients and treated either at just above for unilateral and bilateral ECT; no
bilateral ECT at low- or evaluated before ECT and threshold or at 2.5 times initial age-related effects seen.
high-stimulus intensity); regularly during and after seizure threshold
free of all medications treatment course
except lorazepam (up to
3 mg/day PRN); age
range, 22–80; mean, 56.4
Black et al. 423 depressed inpatients Retrospective chart review using Modified ECT given 3 times/week; Patients rated as recovered (n # 295)
(1993) between 1970 and 1981 multiple logistic regression to bilateral, unilateral, mixed older than those rated as
identify response predictors courses included unrecovered (n # 128)
Sackeim et al. 52 inpatients with major Double-blind, prospective study Bilateral or right unilateral Low-dosage right unilateral ECT
(1987a, b) depression randomized comparing low-dose, titrated modified ECT 3 times/week; ineffective; regardless of ECT
to unilateral or bilateral bilateral and unilateral ECT; patients titrated and treated at modality, age unrelated to clinical
ECT; patients free of all patients evaluated before ECT just above threshold outcome
medications except and following treatments 1, 3, 5,
lorazepam (up to 3 6 and every treatment thereafter
mg/day PRN); age range,
25–83; mean, 61.3
Coryell & 31 patients with unipolar Prospective study of ECT response Most treatments unilateral; most Age independently associated with
Zimmerman depression selected predictors; ratings made on patients had at least 6 outcome on more than 1 of 3
(1984) prospectively HAM- D at weekly intervals by treatments; patients with fewer outcome measures; superior outcome
blind raters than 4 treatments excluded in older patients
Rich et al. Data from 2 groups of Prospective study of response rate to Modified ECT given 3 times/week; Age associated with longer time to
(1984) patients pooled: 66 with conventional ECT by identifying right unilateral ECT used $80% achieve response; study flawed by use
major depressive point of maximal improvement; of patients; mean no. of of different rating scales and
episode or organic patients rated on HAM-D before treatments for each of 2 groups different ECT devices for 2 groups
affective syndrome; first ECT and at 36–48 hours after 8.6 and 8.3
antidepressant each treatment
medications either
stopped prior to ECT
or held constant
Fraser & 29 depressed (Feigner Prospective, double-blind, Modified ECT with twice-weekly No age difference between good and
Glass criteria) elderly (64–86 randomized study; postictal treatment until patient well or moderate outcome groups
(1980) years) randomized to recovery times, memory changes, ECT stopped
unilateral or bilateral ECT and clinical improvement
assessed by HAM-D
Heshe et al. 51 patients with endogenous Prospective blind evaluations before Either modified unilateral (average In patients over 60, significantly better
(1978) depression randomized to ECT, at end of ECT, and 3 months 9.2 treatments) or bilateral ECT therapeutic effect from bilateral than
unilateral or bilateral ECT after final treatment (average 8.5 treatments), twice unilateral treatment; regardless of
weekly, number of treatments modality, satisfactory results in 75%
decided by treating clinician of patients $60 years and 96% of
Chapter 13 / Electroconvulsive Therapy in Late-Life Depression
Herrington 43 consecutive severely Patients rated on day before ECT given twice weekly for total of Age unrelated to outcome
et al. depressed patients (aged treatment and weekly thereafter 6–8 treatments
(1974) 25–69) randomized to ECT for 4 weeks
or l-tryptophan (up to 8
g/day); 40 patients included
in efficacy analysis
Strömgren 100 patients with endogenous Prospective, double-blind study Minimum of 6 treatments given; Of 53 patients aged 19–44, 17 were
(1974) unipolar or bipolar contrasting unilateral and duration of current resistant; 7 of 47 aged 45–65 were
Part IV / Affective Disorders
depression; aged 19–65; bilateral ECT individualized; average of 9 resistant–a significant difference
patients drug-free except treatments given to younger efficacy superior in older patients for
for hypnotics and mild patients, 8.7 to older patients both bilateral and unilateral ECT
sedatives
Folstein et al. 118 consecutive patients who Retrospective chart review: progress Nature and duration of ECT not Improvement related to older age and
(1973) received ECT; diagnoses of notes at time of discharge rated as described shorter hospital stay; no significance
schizophrenia, neurotic to whether or not patient improved tests provided; mean age of improved
reactions, and affective patients (n # 86) 50, compared with
disorders 31 inpatients rated not improved
(n # 32)
Mendels 53 consecutive inpatients Prospective study: patients rated with 4–11 treatments (mean 6.4) with Superior outcome in patients over 50 at
(1965a, evaluated pre-ECT and 1 HAM-D; evaluators not blind to modified ECT 3-month follow-up but not at
1965b) and 3 months post- ECT; treatment history 1-month follow-up
age 21–76, mean 48.8
Carney et al. 129 depressed inpatients Prospective study to establish Patients received 3 or more Better response in endogenous
(1965) predictive factors; patients scored treatments depressives at 3 and 6 months (per
for presence or absence of 35 factor analysis); in patients over 40,
features, followed up at 3 and 6 type of depression not associated
months post-ECT; outcome with outcome
criteria defined
Nystrom 2 series of patients: 254 in Prospective, blind evaluation; Modified bilateral ECT at 2 Lund series: positive association
(1964) Gothenburg series, 188 outcome criteria specified treatments/week initially; between age and degree of
in Lund; most cases average number in Lund series improvement in females; Gothenberg
depressed but other 6.9, 4.4 in Gothenberg series: age !25 years negatively
diagnoses included related to outcome
Greenblatt 128 patients randomized Prospective study compared ECT and ECT modified by succinylcholine Medications and ECT equally effective
et al. to 4 treatment groups; antidepressant medications; given 3/weekly for 3 weeks in youngest age group; ECT
(1962) diagnosis of schizophrenia, explicit outcome criteria used minimum, more at discretion of significantly more effective than
psychoneurotic and psychiatrist medications in oldest age group
psychotic depressive
reactions, involutional
psychosis; 28 received ECT;
age 16–70, mean 46
Ottoson 44 (18 males, 26 females) with Prospective study with blind raters; Modified bilateral ECT with Age not significantly related to efficacy;
(1960) endogenous depression; efficacy evaluated by outcome 1 intervals between first 3 therapeutic response later in older
age 36–70, mean 55.8 week after 4th treatment, 1 week treatments of 2–4 days and patients
after end of ECT course, and total between following treatments of
number of treatments required 3–7 days; dose adjusted upward
for age; patients divided into 2
groups: one received stimulus
grossly above threshold, one
moderately above threshold
Hamilton & 49 hospitalized male patients Patients assessed prospectively and 1 Usual course 6 treatments, Age unrelated to Outcome
White with severe depression; age month after end of ECT maximum 10; 14 patients had
(1960) range 21–69, mean 51.7 second course
Roberts 50 patients, women 41–60 Prospective study of predictors of Twice weekly modified ECT until Symptom scores at 1 month: significant
(1959a,b) years ECT response; patients scored on maximum benefit; averaged inverse correlation with age (older
clinical features prior to ECT and between 7 and 8 treatments women more improved); no
presence or absence of symptoms correlation at 3 months
at 1 and 3 months post-ECT
Chapter 13 / Electroconvulsive Therapy in Late-Life Depression
(continued)
393
394
Herzberg 227 cases selected from all Retrospective chart review of patients Nature and duration of ECT not Superior outcome or sustained
(1954) patients who had received rated for initial response to ECT, described improvement in patients in 4th
ECT; diagnoses of continued response, no relapse decade compared with patients in
schizophrenia, manic after discharge other age groups
Part IV / Affective Disorders
depressive psychoses,
involutional melancholia
Hobson 150 patients at Maudsley Prospective study to identify Nature and number of ECT Age unrelated to outcome; several
(1953) Hospital; no diagnostic predictors of ECT response; treatments not described other predictors identified
criteria used, but almost patients categorized as either free
all cases were depressed; of symptoms or still having
127 included in analyses marked symptoms after ECT
Rickles & 200 private patients treated Retrospective study of why patients Usual course 10–12 treatments; Authors felt that ECT failed if patient
Polan with ECT; diverse failed ECT; treatment considered patients with schizophrenia also was menopausal or postmenopausal;
(1948) diagnostic categories failed when improvement not received 24–40 subcoma insulin statistics not presented
included schizophrenia maintained for at least 1 year shocks
Gold & 121 consecutive male Prospective study of outcome Type and number of treatments Superior clinical outcome in older age
Chiarello patients, 103 diagnosed as predictors and outcome; patients not described groups
(1944) schizophrenic; age range placed in 1 of 4 categories from
15–60 much improved to no change
patients later develop a dementing ill- tients with psychotic depression. How-
ness.88 ever, recent experience suggests that
Elderly patients with psychotic depres- high-dosage right unilateral ECT is at least
sion respond less positively to pharmaco- as effective as bilateral ECT, with less long-
logic treatment (particularly monother- term amnesia, which usually accompanies
apy) but more positively to ECT than bilateral electrode placement. In the case
nonpsychotic patients.89 Specific delu- of right unilateral ECT, high dosage is de-
sions, in addition to vegetative or melan- fined as treatment at least 6 times the sei-
cholic symptoms, predict favorable re- zure threshold. In the case of bilateral
sponse,19,70,90–93 as may psychomotor ECT, high dosage is defined as 2.5 times
disturbance.67,94 In elderly patients with the seizure threshold (Figure 4).
psychotic depression, observation of early The average number of ECT treat-
resolution of delusions, appetite and ments given to patients of all ages in the
sleep disruption, with later improvement United States in previous years for major
in subjective mood and feelings of self- depression was approximately 6; at pres-
worth is common. Certain delusional ele- ent, the average is approximately 8 to 9
ments (bizarreness, effect on behavior, (possibly indicating increasing ECT treat-
strength of delusional conviction, insight ment resistance) and the use of lower-in-
into delusional thoughts) may take longer tensity stimulation. Some depressed pa-
to improve, with gradual recession during tients only begin to show clinical benefit
the course of ECT. after an extended ECT course, i.e., 10 to
Traditionally, bilateral ECT has been 12 treatments. Other elderly depressed
the standard treatment for elderly pa- patients with psychosis who do not im-
Figure 13.4. Initial seizure threshold as a function of age for 245 patients treated with right
unilateral ECT (From Boylon LS, Haskett RF, Mulsant BH, et al. Determinants of seizure threshold
in ECT: benzodiazepine use, anesthetic dosage, and other factors. J ECT 2000;16:3–18). The line
at the diagonal represents the dosage patients would receive based on age-based dosing, e.g.,
50% of device output for 50-year-old. The lower line is the fit of the regression of age on seizure
threshold. While there is a significant relationship (r ! 0.19 for raw values), there is marked
variability. Dosing based solely on age provides a poor approximation of dosing needs and results
in the greatest over-dosing in the oldest age patients.
Chapter 13 / Electroconvulsive Therapy in Late-Life Depression 397
elderly patients, an organic mental syn- fects. Patients vary considerably in the de-
drome characterized by marked disorien- gree of cognitive impairment, regardless
tation.170,174 The development of a severe of how ECT is administered.
organic mental syndrome often results in
Individual Correlates of Cognitive
interruption or premature termination of
Dysfunction
ECT since patients, relatives, and clini-
cians are unwilling to risk further deterio- Two key clinical questions arise regarding
ration of mental status functioning.175 ECT-induced cognitive impairment: (1),
Within days of ECT termination, el- are there signs during the ECT course that
derly depressed patients often manifest predict which patients will develop more
superior cognitive performance relative severe and/or persistent short- and long-
to their pretreatment baseline. Intelli- term cognitive deficits and (2), can we
gence test scores for all age groups, in- identify the patients most at risk for severe
cluding the elderly, may even be higher and/or persistent amnesia prior to the
shortly after ECT relative to scores in the start of ECT?
untreated depressed state.148,176 More Over the 70-year history of convulsive
than a week or two following the end of therapy, numerous investigations of the
the ECT course, differences in the cogni- technical factors that influence the de-
tive effects of bilateral and right unilateral gree of cognitive side effects have been
electrode placements are difficult to dis- conducted. Surprisingly, only in the last
cern in domains other than retrograde few years has investigation focused on the
amnesia.27,59,148,164,165 Early evidence of patient factors that predict the variability
improved cognition following ECT is in these deficits. Some patients will take
manifested in patients’ activities. After a twice or three times as long to reorient
few treatments with ECT, elderly individu- and be capable of leaving the recovery
als may begin to read books, attend group room; others will develop an organic men-
meetings, and become capable of follow- tal syndrome, a continuous confusional
ing complex instructions. However, de- state.170,171 Although rapid improvement
spite this improvement in attention and in global cognitive status immediately fol-
concentration, elderly patients still may lowing termination of ECT will occur, pa-
not retain information after a brief time tients with prolonged postictal disorienta-
period. This anterograde amnesia typi- tion are likely to develop the most severe
cally resolves within a few weeks of ECT and persistent retrograde amnesia.
termination.59,148 It is doubtful that ECT A range of retrospective studies indi-
alone ever causes a persistent deficit in an- cates that patient age and medical status
terograde amnesia.59,177 Not infrequently, are also predictors of the development
elderly inpatients will repeatedly request of persistent confusion during the ECT
information about a pass for the weekend course.20,57,103,110,111,113,175,180 Older pa-
or an expected visit from a relative tients and those with compromised medi-
whereas memory for more remote events cal status are most at risk for prolonged
is intact. Patients may have difficulty re- confusion during the course of ECT.
calling events that occurred during treat- Older depressed patients experience
ment, and months or, in rare instances, more severe anterograde and retrograde
years prior to the ECT course.178 amnesia immediately following the end of
Retrograde amnesia gradually disap- ECT relative to younger patients, with
pears so that over time more distant mem- some differences persisting at one-month
ories, seemingly ‘‘forgotten’’ immediately follow-up.181 Elderly patients with preex-
following the treatment course, subse- isting cognitive impairment, even outside
quently return.163,165,177,179 However, in the context of frank neurologic disease,
some patients amnestic effects of ECT per- are at risk for more prolonged retrograde
sist,27,163,165 most likely due to a combina- amnesia and require appropriate modifi-
tion of retrograde and anterograde ef- cation of ECT technique to lessen cogni-
400 Part IV / Affective Disorders
tive deficit (see Table 13.2). Global cogni- Electrode Placement and Cognitive
tive impairment seen in the depressed Dysfunction
state also increases vulnerability for the Over the past 30 years, one of the most
amnestic effects of seizure induction. For controversial aspects of ECT administra-
example, elderly pseudodemented pa- tion has been the anatomic positioning of
tients87 often show dramatic improve- stimulating electrodes, specifically the use
ment in global cognitive status during and
of bilateral and right unilateral ECT. This
following ECT but are at increased risk
debate has centered on possible differ-
for more prolonged and deeper amnesia.
ences in efficacy as well as experience sug-
Consequently, baseline cognitive impair-
gesting that bilateral ECT accentuates
ment in the elderly depressed patient may
long-term amnesia.48,149,186,187 That bilat-
denote a subgroup whose memory func-
eral ECT results in more profound acute
tion is more fragile and likely to be af-
and short-term cognitive impairment
fected by ECT.
rather than right unilateral ECT is widely
Technical Administration recognized.148 In the immediate postictal
A variety of technical factors associated period, the duration of disorientation will
with ECT administration determine the be considerably longer after bilateral rela-
degree and persistence of the cognitive tive to right unilateral ECT position-
side effects. These include the nature of ing.59,169,170,188 During treatment and in
electrical waveform, anatomic positioning the days following ECT termination, bilat-
of stimulating electrodes (electrode eral ECT will result in greater retrograde
placement), electrical stimulus intensity, amnesia for personal and general in-
spacing or frequency of treatments, total formation.59,163–165 Anterograde amne-
number of treatments, duration of sei- sia—verbal memory in particular—will
zures, type and dosage of anesthetic also be greater following bilateral
agent, adequacy of oxygenation, and use ECT.59,151,165,189 Compared to depressed
of concomitant medications.5,148 Table patients treated with medications, pa-
13.2 summarizes the steps that can be tients treated with right unilateral ECT do
taken to minimize cognitive side effects by not show greater retrograde amnesia for
altering ECT technique. autobiographical information 6 months
In recent years, sine wave stimulation after the ECT course.165
has been replaced by standard brief-pulse Bilateral ECT is usually reserved for
stimulus, which dramatically reduces the psychiatric or medical emergency or for
acute cognitive side effects of ECT. (see medically high-risk patients for whom the
Figure 6) Another recent modification, number of treatments must be mini-
ultrabrief pulse stimulation, reduces ad- mized. When bilateral ECT is adminis-
verse cognitive effects.182–185 Ultrabrief tered, a switch to right unilateral ECT
pulse (0.3 ms) right unilateral ECT ad- should be considered for patients exhibit-
ministered at 6 times initial seizure thresh- ing substantial clinical progress but unac-
old is comparable in efficacy to standard ceptable cognitive side effects. When right
pulse width (1.5 ms), bilateral (2.5 " ST), unilateral ECT is ineffective, increased
or right unilateral (6 " ST) ECT. In con- stimulus dosage should be considered be-
trast, ultrabrief pulse (2.5 " ST) bilateral fore a switch back to bilateral ECT.
ECT lacks efficacy and has markedly infe-
rior therapeutic effects than right unilat- Stimulus Dosing and Seizure
eral ECT. Because ultrabrief right unilat- Threshold
eral ECT (0.3 ms and 6 " ST) is highly Three factors reliably predict seizure
effective and has a profoundly reduced threshold: electrode placement, gender,
side-effect profile, it is likely to become and age.60–62,190–192 In males relative to
widely adopted as the ‘‘standard’’ ECT females, and in older patients, seizure
treatment. threshold is higher with bilateral place-
Chapter 13 / Electroconvulsive Therapy in Late-Life Depression 401
Stimulus Sine wave stimulation Use square wave, brief pulse Weiner et al. (1986)
waveform grossly increases stimulation Daniel & Crovitz (1983a)
cognitive side effects Valentine et al. (1968)
Electrode Standard bilateral Switch to right unilateral McElhiney et al. (1995)
placement (bifrontotemporal) ECT Sackeim et al.
ECT results in more (2000, 1993, 1996)
widespread, severe, Weiner et al. (1986)
and persistent cognitive Daniel & Crovitz (1983b)
side effects
Stimulus Grossly suprathreshold Adjust stimulus intensity Sobin et al. (1995)
dosage stimulus intensity to needs of individual Sackeim et al. (1993)
increases acute and patients by dosage Sackeim et al. (1986)
short-term cognitive titration Squire & Zouzounis
side effects (1986)
Number of Progressive cognitive Limit treatments to Calev et al. (1991)
treatments decline with high- number necessary to Sackeim et al. (1986)
intensity treatments achieve maximal clinical Daniel & Crovitz (1983a)
(sine wave, bilateral, or gains Fraser & Glass (1978,
grossly suprathreshold) 1980)
Frequency More frequent treatments Decrease frequency of ECT Lerer et al. (1995)
of treatments (3–5 per week) result McAllister et al. (1987)
in greater cognitive
deficits
Oxygenation Poor oxygenation can Pulse oximetry to monitor APA (2001, 1990)
result in hypoxia and oxygen saturation and Holmberg (1953)
increased cognitive administer 100% 02 prior
deficits to seizure induction
Concomitant High anesthetic dose Reduce anesthetic dose to Mukherjee (1993)
medications may increase cognitive produce light level of APA (2001, 1990)
effects, which some anesthesia; decrease or Small & Milstein (1990)
psychotropics can discontinue psychotropic Miller et al. (1985)
augment dosage; discontinue
lithium prior to ECT
Adapted from American Psychiatric Association Task Force on ECT. The practice of ECT: recommendations
for treatment, training, and privileging. Washington, D.C.: American Psychiatric Press, 2001, with permission.
a
Complete reference citations at end of chapter.
ment than with right unilateral electrode may partially redress this issue. Since this
placement. However, the combined pre- form of stimulation is considerably more
dictive power of these features is insuffi- efficient, seizure thresholds are much re-
cient to base choice of electrical dosage duced, allowing greater effective range
on a formula.5,192,193 Regardless of dosage for dosing relative to threshold.
choice, patients with the highest seizure The efficacy of right unilateral ECT is
thresholds are predominantly elderly especially sensitive to electrical dosage.
males, especially those with cardiac dis- When stimulus intensity is near the sei-
ease.194 The use of ultrabrief stimulation zure threshold, right unilateral ECT lacks
402 Part IV / Affective Disorders
frequency and number of treat- tropic agents may increase cognitive side
ments.20,110,172,188,202 Some clinicians re- effects. Benzodiazepines and anticonvul-
duce the frequency of treatment to twice sant medications may also interfere with
weekly in elderly patients who show pro- efficacy by raising seizure threshold.217,218
gressive clinical improvement but exces-
sive cognitive deficit.
ECT for Depressed Patients with
Concomitant Medications and Neurologic Disorders
Cognitive Effects
Increasingly, ECT is used to treat psychiat-
Evidence suggests that the dose of anes-
ric manifestations in a variety of patient
thetic agent may contribute to the severity
populations with frank neurologic illness,
of cognitive impairment during the post-
including Parkinson’s disease,219–225
ictal recovery period.203 Not surprisingly,
poststroke depression,226–228 and to a
excessive anesthetic dose may result in
lesser extent, dementing disorders.229,230
prolonged postictal disorientation. For
Across a variety of neurologic disorders,
this reason, older patients should receive
ECT is effective in the treatment of pri-
lower doses of anesthetic agents than
mary or secondary mood disorders. In the
younger patients. This is particularly im-
case of Parkinson’s disease, ECT fre-
portant since the dose of the anesthetic
quently exerts beneficial effects on as-
may also alter seizure duration and inten-
pects of the movement disorder and has
sity.60,204
been used as a primary treatment for the
A small dose of a muscarinic anticho-
neurologic condition. Duration of the an-
linergic agent (0.4–0.8 mg atropine or
tiparkinsonian effects is, however, unpre-
0.2–0.4 mg glycopyrrolate) is commonly
dictable; some patients lose benefit within
administered intravenously in ECT, just
days, while others maintain improvement
prior to the anesthetic agent. The anticho-
in the movement disorder for months or
linergic agent serves to block vagal out-
longer.231 The role of continuation or
flow and limit the bradycardia produced
maintenance ECT in sustaining improve-
by the ECT stimulus. This is especially nec-
ment in the movement disorder is largely
essary whenever the possibility of subcon-
undocumented, although clinical experi-
vulsive stimulation exists, or when patients
ence indicates that such long-term treat-
are administered a !-blocker.100 Atropine
ment can be highly effective. Patients with
is preferred to glycopyrrolate since pro-
Parkinson’s disease who receive ECT may
tection against bradycardia is less certain
be at increased risk for prolonged confu-
with glycopyrrolate. In addition, inci-
sion or delirium.232,233 ECT is also effec-
dence of postictal nausea is also higher
tive in treating poststroke depression and
with glycopyrrate,205,206 and glycopyrro-
major depression in the context of de-
late holds no advantage with respect to
menting illness,229,230 although there is
cognitive effects during ECT.205–211
risk of increased severe cognitive side ef-
In sensitive elderly patients, a variety of
fects.
psychotropic agents may intensify the ad-
verse cognitive effects of ECT. Lithium
carbonate, for example, causes acute con- CLINICAL VIGNETTES
fusion during ECT in approximately 1 in
15 patients; more rarely, status epilepticus Case 13.1
occurs.212–216 Lithium should be discon-
tinued prior to the start of an ECT series, Ms. A., a 71-year-old married retired school-
or it can be withheld the night and morn- teacher, was seen in consultation regarding a
serious chronic depression. Over the course of
ing before an ECT treatment. In the el- her adult life, she had suffered many such
derly, concurrent use of benzodiazepines, depressions that were always characterized by
neuroleptics, or other sedating psycho- extreme anergia, anhedonia, and a sense of
404 Part IV / Affective Disorders
pointlessness. Ms. A. was never psychotic and during the memory loss. This is consistent with
never suicidal, but her diminished energy would observations of clinicians experienced with use
often reach such severe proportions that she of ECT who have noted that some patients’ re-
was unable to get out of bed for long periods sponse to ECT does seem to produce a better
during the day. She maintained her weight by remission than chemical antidepressants,
forcing herself to eat, but no longer enjoyed the which may produce only a response or a partial
preparation or taste of food or, indeed, any- response.
thing else. What was most striking to her was her
subjective loss of interest in her grandchildren.
Untreated, these depressive periods could last Case 13.2
up to one year. Typically, however, although
Ms. A. would begin to feel some symptomatic Mr. B., a 76-year-old widowed attorney, devel-
relief after a few months, a chronic pessimism oped a classical syndrome of severe major
and dysphoria persisted even in the absence depression with melancholia. His first symptoms
of serious depressive symptoms (double of depression appeared at the age of 73 after
depression). partial retirement from his law firm. Treatment
with desipramine 85 mg daily (blood level of
Over the course of her life, Ms. A. had been 140 ng/mL) led to dry mouth and mild urinary
treated with at least one antidepressant from hesitancy; intravenous pyelogram revealed no
each class of medication and had responded significant residual urine. After approximately 4
at least once to each. She had successful trials weeks on desipramine, Mr. B.’s symptoms of
of imipramine, fluoxetine, venlafaxine; her re- depression remitted, although a feeling of
sponse to monotherapy with nefazodone, mir- ‘‘mild uneasiness’’ remained. He was able to
tazapine, and bupropion was nontherapeutic. return to work for a few hours a week and re-
She never took an MAO inhibitor and never had sumed most of his social activities. Approxi-
lithium augmentation. mately 3 months after the initial response, Mr.
B.’s ‘‘uneasiness’’ intensified and became par-
At the time she presented for evaluation, Ms. ticularly prominent in the morning. Finally, de-
A. was in a state of profound melancholic, pressed mood and feelings of hopelessness as
nonpsychotic depression. Out of desperation, well as insomnia and appetite loss developed
she requested a consultation regarding ECT over a period of 2 months despite mainte-
and agreed to a course of treatment. She ini- nance therapy with desipramine together with
tially received 2 bilateral treatments, and then supportive psychotherapy.
was given 4 more treatments applied to the uni-
lateral nondominant hemisphere on a thrice- Severe exacerbation of his depressive symp-
weekly basis. Ms. A.’s response was rapid and toms followed some changes in Mr. B.’s law firm.
dramatic. After the first 2 treatments, she no Desipramine dosage was raised to a blood
longer remained in bed and began actively to level of 182 ng/mL; later, thyroid augmentation
participate in family life. By the sixth treatment was attempted with triiodothyronine (up to 50
she proclaimed herself to be ‘‘back to nor- mg daily) for 2 weeks. Because no change in
mal.’’ Based on evidence regarding high rates his mental status occurred, triiodothyronine was
of relapse following ECT, Ms. A. was placed on discontinued, and lithium augmentation was
a low dose of lithium carbonate (600 mg; blood attempted, with dosage gradually increased
level 0.4) for maintenance. She remained to 600 mg daily (blood level of 0.75 mEg/L). De-
depression-free at one-year followup. pressive symptoms were ameliorated approxi-
mately 3 weeks after the introduction of lithium,
This case illustrates the importance of consider- but he developed tremor and unstable gait
ing this most useful antidepressant treatment that required reducing the dosage to 300 mg
even for older patients who have had chronic daily (blood level of 0.44 mEg/L). Mr. B. re-
depression over the course of a lifetime. Her mained partially symptomatic with mildly anx-
treatment also illustrates the usefulness of post- ious and depressed mood, particularly in the
ECT lithium maintenance to prevent relapse. Al- morning, with early morning awakening and
though Ms. A. experienced impairment of re- complaints of poor concentration.
cent recall for the period during and prior to
the ECT, she reported that this memory loss was Approximately 2 months after the improvement
a small price to pay for the dramatic improve- induced by lithium, Mr. B.’s depression wors-
ment in her mood. Like other older patients ened severely; suicidal ideation developed,
whose depression has responded to ECT, she and he was hospitalized in a geriatric psychiatry
also indicated that the quality of the response unit. Psychotropic drugs were discontinued,
to treatment was better than that from chemi- and 10 unilateral ECTs were administered, re-
cal antidepressants. She stated that her mood sulting in complete remission of his depression.
and thinking felt ‘‘clearer’’ following the ECT Sertraline, 50 mg daily, was started immediately
Chapter 13 / Electroconvulsive Therapy in Late-Life Depression 405
after the last ECT and increased to 75 mg 5 days After a fall, Mrs. C. sprained her right ankle, and
later. This drug was chosen because the tri- her mobility decreased for 2 to 3 weeks. During
cyclic antidepressant desipramine had failed this time, she became apathetic, lost interest in
to maintain Mr. B.’s remission. However, 3 weeks television or socialization, and developed in-
after the last ECT, Mr. B. began again to experi- somnia and appetite loss. After a diagnosis of
ence depressed mood, early morning awaken- depression, imipramine was begun, with dos-
ing, and suicidal ideation. Sertraline was dis- age increased by 25 mg every other day up to
continued a week later, and three additional 75 mg daily. After 6 days on imipramine 75 mg,
unilateral ECT treatments were administered, Mrs. C. developed agitation, confusion, inabil-
with excellent response. Although therapy with ity to sustain her attention, and incoherent
MAOIs was considered, maintenance ECT was speech. Her symptoms were significantly worse
chosen because his rapid development of sui- at night; she appeared frightened and kept
cidal ideation and lack of supervision after dis- saying that her neighbors were coming to ‘‘put
charge placed him at risk. Compliance with her away.’’ Her face was flushed, her skin dry,
MAO diet was also a concern, especially during and her pulse was 120 beats per minute.
the period after ECT when his memory was im-
paired. Maintenance ECT was given every 2 Mrs. C. was admitted to an acute psychiatric
weeks during the first 2 months and then unit with a diagnosis of anticholinergic delirium.
monthly. Nine months after completion of the Imipramine was discontinued, a course of hy-
initial ECT trial, Mr. B. was still asymptomatic. dration was begun, her vital signs were moni-
tored closely, and her pulse decreased to 95
Some depressed geriatric patients respond well
to antidepressant treatment but cannot sustain beats per minute within 24 hours. Three days
remission despite continuation therapy with later, her confusion and agitation lessened, but
antidepressant drugs. Mr. B.’s major depression the symptoms of depression were even more
with onset in late life responded favorably to apparent. She gradually developed severe
desipramine, desipramine combined with lith- psychomotor retardation and began refusing
ium, and a trial of ECT at various times. How- to eat or drink. Treatment with desipramine, 10
ever, approximately 1 to 3 months after initial mg daily, began and was increased by 10 mg
improvement, his depression returned, necessi- every 3 days. A week later, Mrs. C. required
tating additional antidepressant treatment. Pa- tube feeding. At 40 mg of desipramine daily,
tients like Mr. B. often are difficult to treat, par- her pulse rate ranged between 100 and 110
ticularly if they cannot tolerate particular beats per minute. At this point, desipramine was
antidepressants or therapies. ECT is usually ef- discontinued, and 5 days later unilateral ECT
fective in such cases and should be consid- was begun. ECT was administered twice a
ered, especially when the patient becomes dis- week, and after a total of eight treatments, Mrs.
heartened by the repeated failures. The C.’s depression was in complete remission.
rollercoaster of hope and disappointment,
coupled with the pessimism of the depressive Elderly patients are sensitive to the anticholiner-
syndrome, may cause the patient to give up gic effect of heterocyclic antidepressants. De-
and facilitate development of suicidal idea- lirium, persistent sinus tachycardia, or urinary re-
tion. tention often lead to discontinuation of these
drugs. When the diagnosis of anticholinergic
Maintenance ECT needs further investigation. delirium is in doubt, physostigmine 1 mg diluted
Many patients, however, remain in remission in 10 mL of normal saline should be adminis-
from depression while receiving ECT every 4 to
tered intravenously over 5 to 7 minutes. The
6 weeks. ECT appears to be a reasonable op-
mental status of patients with anticholinergic
tion for patients with severe depression who fail
delirium improves almost immediately. How-
to remain in remission while on an adequate
ever, physostigmine should be avoided for very
dosage of a heterocyclic antidepressant, a se-
old patients or those with cardiac disease be-
rotonin-reuptake inhibitor, or an MAOI. Only de-
cause it may cause sinus brachycardia or tran-
pressed patients who are able to tolerate and
sient sinus arrest. Patients with bronchial asthma
respond to a trial of ECT should be considered
for maintenance ECT. may develop bronchospasm after administra-
tion of physostigmine.
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