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Psychiatric Times
Refinements in ECT Techniques
April 19, 2013 |Electroconvulsive TherapyByKaron Dawkins, MD
Electroconvulsive therapy (ECT) has been practiced since 1938 and is one of the best-studiedtreatment modalities. Because of its long history it has been the comparator for a number ofsubsequent therapies including pharmacological and other somatic interventions. Even with ECThowever the response rate for treatment-refractory patients is sobering and the treatment is notwithout risks and adverse effects.
1Still it can be effective when other interventions have failed.
Treatment-refractory major depression is the primary indication for ECT although ECT may haveparticular utility in psychotic depression catatonia and suicidality as well.2 The AmericanPsychiatric Association (APA) guidelines also list an indication for schizophrenia.
3
The Case Vignette illustrates a fairly typical case for ECT referral and the pati ent is a reasonablecandidate.
CASE VIGNETTE
John 55 years old is referred for ECT evaluation. He has a long history of recurrent majordepression (including in childhood) with onset of the current episode 6 months earlier. He presentswith depressed mood anxiety middle insomnia social isolation marked fatigue significantanhedonia and profound loss of interest and motivation. His concentration attention and short -term memory are also negatively affected. His appetite is normal and his weight is stable. He denies
suicidal ideation and past suicide attempts but acknowledges thinking that his life is pointless. He
denies psychotic or manic symptoms. He is having problems at work and there is significant maritaldiscord at home.
John first sought treatment in his early 30s. He has taken a number of antidepressants of differentclasses some of which worked partially until they lost their effectiveness or he had unacceptableadverse effects. He desperately wants symptom relief as soon as possible but is very concernedabout cognitive adverse effects of ECT.
To suppress the electrically induced tonic-clonic motor seizure activity and thus minimizemusculoskeletal complications paralytic agents are administered. Because conscious paralysiswould be very distressful patients receive general anesthesia. ECT entails a series of treatmentstypically 6 to 12 to achieve response or remission. Cognitive adverse effects are the major concernespecially for patients and their families.45 Even with full remission relapse rates remain highparticularly for the nonpsychotic medicationresistant population.1 Generally once symptomremission is achieved ECT is frequently discontinued. However some patients get continuation (toprevent relapse) or maintenance (recurrence prophylaxis) ECT.
367
When to refer
The decision to pursue ECT is based on a number of factors including diagnosis type andseverity of symptoms treatment history consideration of the anticipated risks and benefits of ECT
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and alternative treatment options and patient preference.3 The principal diagnostic indication isunipolar or bipolar depression. Policies and procedures should be developed to ensure properinformed consent including when how and from whom consent is to be obtained and the natureand scope of information to be provided. . . . Informed consent should be obtained from the patient
except when the patient lacks capacity to consent.3
There is evidence to suggest that a significant number of patients referred for ECT have not had
adequate medication trials.689 The response rate for patients who are not medication-resistant ishigher up to 90% in one multisite study (log-linear analysis x2 = 6.82 df = 1 P = .009) with sitedifferences in the rates of patients classified as medication-resistant patient age Hamiltondepression scores and total number of ECT sessions.
The global rating of reliability did not differ among patients who were classified as medication-
resistant and having inadequate pharmacotherapy before ECT.8
The FDA efficacy review estimated
the overall treatment effect to be 78%.10 For treatment-refractory patients the ECT response ratemay be about 50% to 60%.
89
Personality disorders comorbid with major depression are common with poorer outcomes with
psychotherapy or pharmacotherapy. Patients with these comorbid conditions are likely to bereferred for ECT. One study examined 139 patients with a primary diagnosis of unipolar majordepression and scores of at least 20 on the 24-item Hamilton Depression Rating Scale; personality
disorders were assessed with a structured interview. Outcomes were compared in patients with no
personality disorder patients with borderline personality disorder and patients with personalitydisorders other than borderline personality disorder. Only 22% of patients with borderlinepersonality disorder met criteria for remission compared with 56% of patients with personalitydisorders other than borderline personality disorder and 70% of patients with no personality
disorder.
Findings from the study indicate that the diagnosis of borderline personality disorder is a predictor
of poor response to ECT (x2 = 11.63 df = 1 P = .001) and has potentially significant implicationsfor the selection of candidates for ECT.
11Still the APA guidelines do not suggest a prohibition of
ECT in patients with comorbid borderline personality disorder. There is a similar stance for patients
with comorbid dysthymia because ECT is rarely used for dysthymia alone.3
ECT can be rapidly effective in mania and catatonia and it can be an early consideration fordepressions with psychotic features. Although antipsychotics continue to be the first-lineintervention ECT can be considered in patients with medication-resistant schizophrenia. Howeverthe probability of significant improvement may be low. There are special considerations for
children and adolescents (additional evaluation from a child and adolescent psychiatrist is
recommended) and for pregnant women (procedural considerations and additional monitoring are
needed).3
Contraindications
Unfortunately some practitioners see ECT as a treatment of last resort whatever the presentingdiagnosis. This kind of thinking on the part of referring psychiatrists and patients is discouraged.There are relative contraindications for ECT but few absolute ones. Many patients present withcomorbid psychiatric disorders for which ECT is not indicated. There are comorbid medical
conditions that also affect the risk to benefit ratio.
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Electrically induced seizures can be associated with transient cardiovascular changes (asytolebradycardia tachycardia hypertension increased myocardial oxygen demand) increasedintracranial pressure increased intraocular pressure release of catecholamines and other effectsthat can exacerbate preexisting conditions. These conditions require optimization of their
management and/or procedural changes to minimize morbidity and mortality.
Precautions must be taken in patients with unstable or severe cardiovascular conditions (eg recent
myocardial infarction unstable angina congestive heart failure uncontrolled hypertension)aneurysm increased intracranial pressure recent cerebral infarction or pulmonary conditions (egchronic obstructive pulmonary disease asthma pneumonia) and in patients who fall into theAmerican Society of Anesthesiologists rating level 4 or 5.3
The mortality rate has fallen over the decades of ECT practice.12 The number of deaths resulting
from ECT is estimated to be 1 per 10000 patients or 1 per 80000 treatments. 3 The VeteransAffairs (VA) National Center for Patient Safety database estimate is less than 1 death per 73400treatments (or less than 1 per 14000 patients). No associated deaths were reported in any VAhospital between 1999 and 2010.
13In California from 1984 to 1994 and in Texas from 1993 to
1998 there were less than 2 deaths per 100000 treatments.1415
TECHNIQUE
The mainstays for the reduction of adverse effects include electrode placement stimulus energy waveform and frequency of treatment (Figure 1).16
Figure 1
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Electrode placement
The two best-studied placements are right unilateral (RUL) and bilateral (BL also known asbitemporal and bifrontotemporal) placements. RUL ECT has fewer cognitive adverse effects than
BL ECT; however unless it is administered well above seizure threshold RUL ECT is lesseffective (double-blind randomized trial P = .054).17 Suprathreshold RUL ECT can approach theefficacy ofBL ECT. In one study the response rates of both were 65%.9 In another study in which
patients were randomized to titrated moderate suprathreshold or fixed high-dose RUL ECT theresponse rates were 39% and 67% respectively (x2 = 5.6 P = .02).18
ECT practitioners must often choose between maximizing effectiveness and minimizing adverseeffects. This prompts some practitioners to use BL placement frequently at high stimulus energyalmost exclusively. Others start with RUL and switch to BL placement ifthere is a lack of responsegenerally after 4 to 6 treatments.19 The APA guidelines suggest reassessing the indication for
continued ECT and making a change in implementation after 6 to 10 treatments if the patient hasslow or minimal clinical improvement. These changes could include switching electrode placement
from RUL to BL increasing stimulus energy and augmentation strategies.3
Semkovska and colleagues20 performed a meta-analysis (with an effort to control for publicationbias) of 39 studies (1415 patients) to clarify the advantages of RUL relative to BL stimulusintensity and time interval between final assessment and cognitive assessment. They found thatcognitive differences associated with electrode placement and stimulus intensity were limited to the
first 3 days after unilateral treatment: effect sizes ranged from 1.10 to 0.21 (95% confidenceinterval [CI] 1.53 to0.67 0.40 to 0.01 respectively).
Within this time frame there were fewer cognitive disturbances compared with BL placement andmore compared with higher stimulus intensity. After this subacute period there were no significantdifferences between RUL and BL and no remaining significant relationship between stimulus
intensity and cognitive performance after RUL ECT. The time interval after final treatment was
predictive of continuous improvement in anterograde episodic memory autobiographical memoryand executive functioning.
Left unilateral ECT is considered an alternative when RUL is contraindicated typically when thereis a skull defect. It is also a consideration for left-handed patients in an effort to avoid stimulationof language centers. However the lateralization of language centers for an estimated 70% of thisgroup of patients is similar to that for right-handed patients; 15% have bilateral representation; andonly 15% are right dominant for language. Handedness may also be an unreliable predictor. While
most practitioners use RUL placement regardless of handedness an alternative strategy is to switchlaterality over the initial sessions to gauge which is associated with fewer cognitive adverse
effects.321
Bifrontal ECT has been investigated as a way to maximize response without increasing cognitive
adverse effects (by avoiding stimulation over the temporal region) and directing treatment towardcircuits in the frontal cortex that may play an important role in depression.
22As described by
Abrams2324 bifrontal placement was initially sidelined because benefits were intermediate; theelectrodes were too close together and there were skin burns secondary to shunting. Interest wasrenewed in the 1990s with a number of published clinical trials and apparent widespread use.
21
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One study showed bifrontal ECT had the best antidepressant (P < .01) and cognitive (P < .05)outcomes and required the fewest treatments compared with BL and RUL ECT. However thedifferential cognitive effects were not evident 3 months after the last ECT.
2526
Bailine and colleagues27
randomized 48 patients to either BL or bifrontal ECT (stimulus titration atfirst treatment subsequent treatments 1.5 times seizure threshold). All 24 patients in the bifrontalgroup and 23 of the 24 patients in the BL group met remission criteria (Hamilton Depression scale
less than 10 first Hamilton Depression scale less than 3 or Clinical Global Impressionimprovement score less than 3) by the 12th treatment. The BL group had a significant decrease in
the mini-mental state score that was considered to be clinically significant albeit small (P = .03).
The researchers attributed efficacy and improved cognitive performance to avoidance of stimulation
over the temporal areas while retaining bilateral stimulation. They also speculated that bifrontal
placement may have the advantage of fewer dental complications since the masseter muscles mayreceive less direct stimulation.
In a double-blind controlled trial Eschweiler and colleagues28 randomized 92 patients to either 6RUL (2.5 times seizure threshold) or 6 BL (1.5 times seizure threshold) sessions. While there was
no difference in the response rate and only a minor cognitive difference between the two groupsonly 12 of the 46 patients (26%) in each group responded (odds ratio tested by Fishers exact testand used to calculate 95% CI; CI 18-36; odds ratio 0.35 to 2.8). The reasons for this low responserate were unclear although this may have been a function of selection bias of a particularlytreatment-resistant population late in the course of their illness.
Kellner and colleagues29
report the results of a large double-blind controlled trial of 230 patientswho were randomized to bifrontal placement at 1.5 times seizure threshold BL at 1.5 times seizurethreshold or RUL at 6 times seizure threshold. Antidepressant outcomes were comparable withremission rates of 55% for RUL (95% CI 43-66) 61% for bifrontal (95% CI 50-71) and 64% forBL (95% CI 53-75). BL placement resulted in a faster reduction of symptoms but there were few
cognitive differences among the 3 treatment arms. The researchers note that BL placement could beused preferentially in urgent clinical situations. RUL placement can be effective at high stimulus
intensity and could be the initial choice if there is concern about retrograde amnesia. Bifrontal
placement did not have a cognitive advantage nor was RUL consistently better than BL placementon cognitive measures.
One potential advantage of bifrontal ECT is a lower risk of bradycardia and asystole compared withBL and standard pulse width RUL ECT. Bifrontal ECT could be considered for patients with
arrhythmia. Ultrabrief pulse width RUL ECT is associated with less bradycardia (P = .004) and
asystole (P = .001) than standard pulse width RUL ECT although the data were collected in thecontext of clinical service via printed ECGs and were not systematically controlled.30
Left anterior right temporal (LART or left frontal right temporal) placement seeks to decreasecognitive adverse effects by minimizing the impact on the temporal/hippocampal areas. Thisplacement is less well studied although in small open and double-blind pilot trials LART hadcomparable efficacy and fewer cognitive adverse effects.
31-33It is not known how widely this
modality is used. Some practitioners use it as an intermediate step between RUL and BL ECT.
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Stimulus energy
It is well established that the stimulus energy must be above seizure threshold (suprathreshold) to
maximize treatment efficacy. Seizure thresholdthe minimum amount of energy to elicit ageneralized seizureis highly variable up to 40-fold in some estimates. Men the elderly and BLplacement tend to have a higher seizure threshold. Seizure threshold is also inconstant because ECT
has an anticonvulsant effect that raises seizure threshold (paired t P < .001). 34 Treatment protocols
vary from titration procedures to fixed-dose strategies because there are different schools of thoughtabout how much above seizure threshold a stimulus should be.
Some practitioners during the first treatment session determine seizure threshold by deliveringincreasingly larger stimuli until a generalized seizure of adequate length (at least 15 seconds as
measured by motor activity or electroencephalogram) is obtained. There are a number of
methodologies by which this stimulus titration is done. Electrode placement sex age dosages ofanesthetics and concomitant medications can be used to predict seizure threshold. 3 Howeverseizure threshold typically increases over the series. Proxies such as seizure length seizure qualityand clinical response are signs that stimulation is no longer suprathreshold and stimulus intensity
should be increased.
Seizure threshold increases with age; thus a method that sets the stimulus energy based on thepatients age can be used.35 Because this might cause patients to be stimulated at higher intensitythan necessary some practitioners use the half age method.28 The APA guidelines recommendthat unilateral treatments be moderately to markedly suprathreshold (2.5 to 6 times seizure
threshold) and that BL treatments be moderately suprathreshold (1.5 to 2.5 times seizure threshold)because the efficacy of BL placement is less sensitive to suprathreshold dosing than is unilateral
placement.3
There have been calls for higher-output machines in the United States to achieve the dosages
required for effective unilateral ECT.36
However whatever the placement higher-energy
stimulation is associated with increased cognitive adverse effects. Manipulation of pulse width mayallow for more efficiency in inducing seizures with fewer cognitive adverse effects.
Waveform
The first ECT apparatus used sine waves which were inefficient in inducing seizures and wereassociated with significant cognitive adverse effects.
537Brief pulse has fewer cognitive adverse
effects without a reduction in efficacy. As a result the APA guidelines state that the continued useof sine wave stimulation is not justified.
3However the ideal pulse width continues to be studied.
The chronaxie or optimal width for neuronal polarization is estimated to be 0.1 to 0.2
millisecond.3839
Until recently most devices had a pulse width range of 0.5 to 2 milliseconds.Ultrabrief pulse width of less than 0.5 millisecond had been considered earlier in ECT history butwas not pursued because of concerns about efficacy. Now there is resurgent interest.
Using a double-masked study Sackeim and colleagues40 sought to determine whether ultrabriefpulse and RUL placement would minimize cognitive adverse effects but not at the expense of
efficacy. Patients were randomized to RUL ECT at 6 times seizure threshold or BL ECT at 2.5
times seizure threshold using brief pulse (1.5 milliseconds) or ultrabrief pulse (0.3 millisecond).The remission rate was 73% for ultrabrief pulse RUL ECT 65% for standard brief pulse BL ECT
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59% for standard brief pulse RUL ECT and 35% for ultrabrief pulse BL ECT (all P < .05 aftercovariate adjustment). The ultrabrief pulse RUL group had less severe cognitive adverse effects (P
< .001).
The researchers concluded that ultrabrief stimulus markedly reduces cognitive adverse effects(acute short-term and long-term) and efficacy can be preserved with markedly suprathresholdRUL ECTefficacy comparable to high-dose BL ECT. There was speculation that the efficacy of
BL ECT may have been improved if stimulus intensity had been greater than 2.5 times the initialseizure threshold although cognitive adverse effects may have also increased.
Niemantsverdriet and colleagues41
compared 0.25-millisecond ultrabrief pulse with 0.5-millisecondbrief pulse in BL ECT. In their study where response was defined as 50% or greater decrease inHamilton depression score and remission as a score of less than 7 73.6% of ultrabrief pulserecipients were responders (42.1% remitters) and 75.6% of brief pulse recipients were responders
(45.6% remitters); no significant difference was found between the two groups (P = .947). Theresearchers attributed different outcomes to study design (retrospective vs prospective) patientpopulation (unipolar depression only vs both bipolar and unipolar depression their sample perhapsmore severely depressed) prior history of ECT (their sample was ECT-naive) and the differences
in the comparator pulse widths (0.25 and 0.5 millisecond vs 0.3 and 1.5 milliseconds).
Sienaert and colleagues42
compared ultrabrief (0.3 millisecond) bifrontal ECT at 1.5 times seizure
threshold with RUL ECT at 6 times seizure threshold. Of the 64 patients 78% were responders (n =50) and 65% (n = 42) were remitters. There was no significant difference in response andremission between the two groups. Not only was there no deterioration in neuropsychologicalmeasures (attention executive function/working memory anterograde episodic memory episodicautobiographical memory and subjective memory) but patients assessed their memory asimproved and there were no significant differences between groups.
The authors caution that ultrabrief ECT may require more sessions (and therefore may produce
more cognitive adverse effects) that perceived memory improvement may be a function ofimproved depression and that only 72.8% of their sample completed the post -ECT battery ofneuropsychological tests.
Loo and colleagues43
compared ultrabrief pulse (0.3 millisecond) at 6 times seizure threshold with
brief pulse (1.0 millisecond) at 5 times seizure threshold in RUL placement in a study limited by its
naturalistic nonrandomized design. The remission rate was lower than that found in the Sackeim40study but the difference was not significant. If those patients who completed treatment with RU LECT only (not switched to BL placement) are considered the response/remission rates were97%/61% for the ultrabrief pulse RUL group and 79%/57% for the brief pulse RUL group.
Patients who received ultrabrief pulse width did require more ECT treatments. However theircognitive measures were superior especially on retention (P < .05) and autobiographical memory(P < .01).
Quante and colleagues44
compared 3 stimulus intensities (4 7 and 10 times seizure threshold) ofultrabrief pulse width (0.3 millisecond) in RUL ECT in a randomized double-blind pilot studylimited by its small number of subjects and lack of acute reorientation data. There was no
significant difference in the response rate: all 3 groups had a significant response to 9 treatments (P
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< .005) although the higher stimulus intensity groups had significant impairment in verbal memory(x2 = 6398 df = 2 P = .041).
There is evidence to suggest that patients who respond to ultrabrief RUL ECT are not clinically
different from other ECT responders.45
Ultrabrief pulse may be a way to increase the effectivenessof RUL ECT by allowing for suprathreshold stimulation without increasing cognitive adverse
effects. It may also allow for lower stimulus intensity in BL ECT which would decrease cognitive
adverse effects while maintaining efficacy.
Frequency of treatments
Cognitive adverse effects tend to accumulate as a function of the frequency and total number of
treatments. Index ECT is done acutely for symptom reduction with the goal of response orremission. In the United States index ECT is typically done 3 times a week usually for 6 to 12treatments. Some patients have dramatic response to the first treatment and significant improvement
after a few treatments while others require more than 12 treatments to achieve maximum response.Index treatments can be done on an inpatient or outpatient basis.
In the United Kingdom and other countries ECT is done twice a week. Lerer and colleagues46found that twice-weekly ECT was just as effective with fewer cognitive adverse effects (P = .05)although the total number of treatments was higher.
Charlson and associates47
performed a comprehensive review and meta-analysis of the existingliterature to examine the efficacy of 2- and 3-times-a-week treatment schedules. Their findings
showed similar efficacy between the two schedules. With the twice-a-week regimen the duration ofeach treatment was longer but the number of actual treatments was lower. Data were insufficient fora pooled analysis of cognitive data but findings suggest that twice-weekly ECT was associatedwith fewer cognitive adverse effects.
Continuation ECT is done weekly to monthly as prophylaxis against relapse which can occur asquickly as 1 week after the last index treatment. In a multisite randomized parallel 6-month trialKellner and colleagues6 compared continuation ECT with pharmacotherapy in patients whoachieved remission after ECT. In the continuation ECT group 37.1% of the patients relapsed and46.1% of the patients maintained symptom remission. In the continuation pharmacotherapy group
(nortriptyline plus lithiuma combination shown to be effective in relapse prevention aftersuccessful ECT1) 31.6% of the patients relapsed and 46.3% of the patients maintained symptomremission. They were statistically equivalent.
In addition more than half of the patients relapsed or dropped out of the study. Better initialinterventions and strategies to prevent relapse are needed. Maintenance ECT can be used long-term
to prevent new episodes much as one would continue effective pharmacotherapy.
COGNITIVE ADVERSE EFFECTS
As a procedure administered under general anesthesia and secondary to cognitive adverse effectswritten informed consent is the standard of care for ECT. A prominent safety concern about ECT is
its cognitive adverse effects which can include acute/short-term as well as long-term cognitiveadverse effects.
1016 According to an FDA review10 patients can experience postictal confusion
that typically quickly resolves and there has been no evidence of persistent disorientation.
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Anterograde memory disturbances typically resolve within 2 weeks. Global cognitive functioning isunchanged or improved within 3 to 6 months compared with baselinethe latter perhaps a functionof improved depression.
Retrograde amnesia both autobiographical and impersonal is a particular concern. The ability toretrieve historical or factual information seems to return to baseline within 6 months but evidenceis inconclusive about personal memory. Autobiographical memory is harder to measure and verify
and can be influenced by depression and comorbid preexisting cognitive disorders. The reports ofloss of autobiographical information are sobering.
1016It is a potential adverse effect that patients
and their families seem to fear most.
Retrograde amnesia with ECT appears to be more problematic than anterograde amnesia. ECT
produces deficits in both autobiographical and impersonal memory but both improve after an ECTcourse. However some patients are left with residual deficits. Retrograde amnesia is worse with BLECT and sine wave stimuli; the extent of retrograde deficits does not significantly correlate withclinical improvement; and measurement is complicated by self-report which correlates better withtherapeutic outcome than more objective measures.
48
A seminal study by Lisanby and associates4 attempted to tease apart the differential effects onautobiographical and impersonal memory. For the cognitive assessments patients with majordepression were randomized to RUL or BL ECT (each at either low or high stimulus energy). The
researchers created the Personal and Impersonal Memory Test (PIMT) to elicit memories of events
4 years before assessment and to rate each personal event for its salience. The PIMT was
administered to affected individuals and controls at baseline during the week after ECT and at 2-month follow-up.
The authors noted that it had been thought that ECT had its most negative impact onautobiographical memory. In contrast they found that deficits were greatest and most persistent forimpersonal memory (knowledge about the world and public events) recent events compared with
distant ones and less salient events. As expected BL ECT produced more profound deficitsespecially for impersonal events (P < .001).
Sackeim and colleagues5
also found that BL ECT caused more severe and persisting retrogradeamnesia 6 months after acute treatment.
OTHER ADVERSE EFFECTS
Common adverse effects can include headache (including precipitation of migraine headaches)musculoskeletal discomfort (including jaw pain and exacerbation of temporomandibular joint
problems) and nausea. There is a risk of injury to teeth and tongue laceration if they are not
adequately protected by a bite block. Cardiovascular adverse effects include bradycardiatachycardia and hypertension. Infrequent but serious complications include postictal agitation oremergence delirium takotsubo cardiomyopathy (catecholamine release causes myocardial stunningand a reversible cardiomyopathy) prolonged seizures and status epilepticus.49 Rarer still is ruptureof the bladder.
5051
The choice of anesthetic agent (eg methohexital propofol ketamine etomidate remifentanil) canhave a differential impact on adverse effects such as nausea and cardiovascular events withoutnecessarily reducing efficacy.
52-55The choice of anesthetic can also influence seizure threshold and
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seizure length which becomes an issue when it is difficult to induce an adequate seizure in patientswith high seizure thresholds. If stimulus energy can be lowered cognitive adverse effects ma y beminimized.
IMPROVING OUTCOMES
The FDA review10
estimated an ECT response rate of 78% but found its impact limited to the acute
phase of less than 4 weeks. Efforts made to improve ECT outcomes include increasing seizurelength with hyperventilation intravenous caffeine and switching anesthetic agents.5657 Howeverseizure length may not correlate with clinical outcome.
The choice of anesthetic agent may have differential effects on cognition. These effects may be a
function of impact on seizure threshold because lowering seizure threshold allows for less stimulusenergy to induce a seizure less energy to stay above seizure threshold and perhaps fewertreatments as a result of this improved efficiency. Some patients get switched to BL placementwhich is associated with more cognitive adverse effects primarily because of an issue with seizurethreshold and seizure length. This is an important consideration if high-dose (either titrated or fixed-dose) RUL ECT can approach the clinical efficacy of BL ECT.
918
Ketamine has garnered interest as an anesthetic agent an antidepressant in its own right and acognitive enhancer with improved short-term memory after ECT.
58Although more research is
needed combining ECT with antidepressants may improve outcomes in some patients.
Sackeim and colleagues59
undertook a prospective triple-masked placebo-controlled study ofpatients who were randomized to nortriptyline venlafaxine or placebo during high-dose RUL ormoderate-dose BL ECT. The patients who received concomitant nortriptyline and venlafaxine hadimproved remission rates without an increase in adverse effects (analysis of covariance [ANCOVA]
on post-ECT Hamilton Depression scores intent-to-treat F2308 = 3.44; P = .03 and completersF2242 = 2.88; P = .06; log-linear analyses on remission rates intent-to-treat P = .04 and completers
P = .02).
Nortriptyline improved remission rates by about 15% and had a slight cognitive advantage (exceptfor measures of retrograde amnesia all other measured cognitive adverse effects were reduced withnortriptyline). Venlafaxine also improved ECT outcomes although less so than nortriptyline with arange of no impact to modestly negative impact on cognition.
The combination of ECT and psychotherapy is also worthy of further investigation because patients
frequently have comorbidities that are not amenable to ECT.60
The data for pharmacologicalattempts to reduce cognitive adverse effects are limited and inconsistent although they arepromising for the cholinesterase inhibitors.
61 With the use of cholinesterase inhibitors initial
concerns about drug-drug interaction with succinylcholine that could prolong paralysis; precipitatebradycardia cardiac arrhythmias and asystole; or prolong seizures have not been widelyreported.
62The study of neuroprotective agents in ECT is intricate because the mechanisms for
ECT-mediated cognitive adverse effects are poorly understood; clinical trials are methodologically
challenging; and a wide range of tools are needed to assess short- and long- term subjective andobjective and anterograde and retrograde (autobiographical and impersonal) cognitive deficits.61
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CONCLUSION
Manipulating stimulus intensity (by lowering seizure threshold) electrode placement (avoidingtemporal areas) waveform (ultrabrief pulse width) and frequency of ECT (consider twice a week ifthere are cognitive adverse effects) and adding concomitant antidepressants may allow improvedresponse as well as decreased adverse effects. However because ECT is frequently used because ofpast treatment failure when conservative implementation fails providers reasonably become more
assertive in all of those parameters. This can increase cognitive adverse effects.
We know ECT is not always effective. The APA guidelines indicate that patients can be considered
nonresponders after at least 10 treatments if optimization efforts are not successful.3 Until there areconsistently better alternatives for severe depression ECT remains a safe and effective intervention.In the interim we will await the findings of the FDA on the classification of ECT devices.Practitioners should use ECT judiciously and take care to minimize adverse effects as much as
possible (Figure 2).
Figure 2
The following are some suggestions for reducing adverse effects of ECT and improving patient
outcomes:
Patients and referring mental health professionals should be educated about the likelihood ofresponse remission and adverse effects: ECT is not globally effective; medication-resistantpatients can be resistant to ECT as well
Prospective patients and their families should be well informed of potential adverse effectsincluding cognitive ones that can persist well beyond index treatment: written informed consent isthe standard of care
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Care should be taken after ECT has started to ensure that patients understand changes in theregimen because they may have already experienced adverse cognitive effects
Cognitive batteries used in research protocols while sensitive are not easily generalized toclinical practice: user- (and resource-) friendly methods of ongoing cognitive assessment would bea boon to patients families and ECT practitioners
If a patient has responded relapse prevention should be assertive regardless of the method that ischosen
References
1.Sackeim HA Haskett RF Mulsant BH et al. Continuation pharmacotherapy in the prevention ofrelapse following electroconvulsive therapy: a randomized controlled trial. JAMA.2001;285:1299-
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2.Kellner CH Fink M Knapp R et al. Relief of expressed suicidal intent by ECT: a consortiumfor research in ECT study. Am J Psychiatry. 2005;162:977-982.
3. American Psychiatric Association Committee on Electroconvulsive Therapy. The Practice of
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techniques/page/0/4#sthash.EwehV4I9.dpuf
[Editor's note: This article was originally published in the February 2012 issue ofPsychiatric Timesas a CME. Now expired as a CME activity, it is published here for educational purposes only]
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