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The Cognitive Effects of Electroconvulsive Therapy inCommunity Settings
Harold A Sackeim*
, Joan Prudic
, Rice Fuller 
, John Keilp
, Philip W Lavori
and Mark Olfson
Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY, USA;
Department of Psychiatry, College of Physiciansand Surgeons, Columbia University, New York, NY, USA;
Department of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA;
Institute for Health, Health Care Policy, and Aging Research, Rutgers University, New Brunswick, NJ, USA;
Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA;
Department of Veterans Affairs Cooperative Studies Program and theDivision of Biostatistics, Department of Health Research and Policy, Stanford University, Palo Alto, CA, USA;
Department of Clinical and GeneticEpidemiology, New York State Psychiatric Institute, New York, NY, USA
Despite ongoing controversy, there has never been a large-scale, prospective study of the cognitive effects of electroconvulsive therapy (ECT). We conducted a prospective, naturalistic, longitudinal study of clinical and cognitive outcomes in patients with major depression treated at seven facilities in the New York City metropolitan area. Of 751 patients referred for ECT with a provisional diagnosis of adepressive disorder, 347 patients were eligible and participated in at least one post-ECT outcome evaluation. The primary outcomemeasures, Modified Mini-Mental State exam scores, delayed recall scores from the Buschke Selective Reminding Test, and retrogradeamnesia scores from the Columbia University Autobiographical Memory Interview–SF (AMI–SF), were evaluated shortly following theECT course and 6 months later. A substantial number of secondary cognitive measures were also administered. The seven sites differedsignificantly in cognitive outcomes both immediately and 6 months following ECT, even when controlling for patient characteristics.Electrical waveform and electrode placement had marked cognitive effects. Sine wave stimulation resulted in pronounced slowing of reaction time, both immediately and 6 months following ECT. Bilateral (BL) ECT resulted in more severe and persisting retrogradeamnesia than right unilateral ECT. Advancing age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits. Thus, adverse cognitive effects were detected 6 months following the acute treatment course. Cognitive outcomesvaried across treatment facilities and differences in ECT technique largely accounted for these differences. Sine wave stimulation and BLelectrode placement resulted in more severe and persistent deficits.
244–254. doi:10.1038/sj.npp.1301180; published online 23 August 2006
electroconvulsive therapy; major depression; memory; cognitive side effects; amnesia
Electroconvulsive therapy (ECT) is widely considered themost effective antidepressant treatment, with medicationresistance its leading indication (American PsychiatricAssociation, 2001). However, critics contend that ECTinvariably results in substantial and permanent memory loss (Breggin, 1986; Sterling, 2000), with some patientsexperiencing a dense retrograde amnesia extending backseveral years (Donahue, 2000; Sackeim, 2000). In contrast,some authorities have argued that, with the introduction of general anesthesia and more efficient electrical waveforms,ECT’s adverse cognitive effects are short-lived, with nopersistent effects on memory (Abrams, 2002; Fink, 2004).Shortly following the ECT course, most patients manifestdeficits in retaining newly learned information (anterogradeamnesia) and recalling events that occurred in the weeks ormonths preceding the ECT course (retrograde amnesia)(Sackeim, 1992; Squire, 1986). Randomized-controlled trialshave shown more severe short-term memory deficits withsine wave compared to brief pulse stimulation (Valentine
et al 
, 1968; Weiner
et al 
, 1986), bilateral (BL) compared toright unilateral (RUL) electrode placement (Lancaster
et al 
,1958; Sackeim
et al 
, 1986; Sackeim
et al 
, 1993; Sackeim
et al 
,2000), and higher electrical dosage (McCall
et al 
, 2000;Ottosson, 1960; Sackeim
et al 
, 1993). These adverse effectsare reduced by the use of RUL ECT with brief or ultrabrief pulse stimulation and electrical dosage titrated to the needsof the individual patient (Sackeim, 2004b). Nonetheless, aminority of US practitioners still use sine wave stimulation,approximately half do not adjust dosage relative to the
Online publication: 12 July 2006 at http://www.acnp.org/citations/Npp071206060157/default.pdf Received 9 March 2006; revised 17 May 2006; accepted 18 May 2006*Correspondence: Dr HA Sackeim, Department of BiologicalPsychiatry, New York State Psychiatric Institute, 1051 Riverside Drive,New York, NY 10032, USA, Tel: +1 212 543 5855, Fax: +1 212 5435854, E-mail: has1@columbia.edu
Neuropsychopharmacology (2007) 32,
2007 Nature Publishing Group All rights reserved 0893-133X/07
patient’s seizure threshold, and a majority administermainly or exclusively BL ECT (Farah and McCall, 1993;Prudic
et al 
, 2004; Prudic
et al 
, 2001). The continueduse of treatment techniques associated with more severeshort-term cognitive deficits may reflect the beliefs thatthe cognitive deficits are transient and that older treatmentmethods provide greater assurance of efficacy (Scott
et al 
,1992).Empirical information about ECT’s long-term effectsderives mainly from small sample studies conducted inresearch settings, with follow-up intervals frequently limitedto 2 months or less. By excluding individuals withsignificant medical and psychiatric comorbidities, use of optimized forms of ECT, and limited statistical power, thesestudies could not adequately assess the severity andpersistence of long-term deficits. In a sample treated incommunity settings, we conducted the first large-scale,prospective long-term study of cognitive outcomes follow-ing ECT. We characterized the profile of cognitive changeimmediately and 6 months following completion of ECT,and examined the relationships of treatment techniqueand patient characteristics to cognitive outcomes. We alsodetermined whether a patient subgroup had especially marked long-term deficits and whether particular forms of ECT administration were overrepresented among thesepatients.
PATIENTS AND METHODSStudy Sites and Study Participation
The study was conducted at seven hospitals in the New YorkCity metropolitan area: two private psychiatric hospitals,three community general hospitals, and two hospitals atuniversity medical centers. A clinical outcomes evaluatorwas assigned to each hospital and collected all researchinformation. The study was conducted by investigators atthe New York State Psychiatric Institute (NYSPI), andpatients at this facility did not participate. InstitutionalReview Boards at NYSPI and each of the seven hospitalsapproved the study.Participants were recruited from the in-patients andoutpatients referred for ECT with a clinical diagnosis of adepressive disorder. Over a 26-month period, 751 patientswere so referred (see Prudic
et al 
(2004) and Figure 1 fordetails on sample composition). Study participants met theDiagnostic and Statistical Manual (DSM-IV) criteria fora major depressive episode (unipolar or bipolar) or schizo-affective disorder, depressed, on the basis of the StructuredClinical Interview for DSM-IV Axis I Disorders (SCID-I/P)(First
et al 
, 1996a). Patients were excluded if they receivedECT in the past 2 months, scored below 15 on the Mini-Mental State Exam (Folstein
et al 
, 1975), or spoke neitherEnglish nor Spanish. Patients were at least 18 years of age
Screened Patients (N = 751)Non-participants (N = 353)Entered Study (N = 398)Excluded from All Analysis (N =51)
16 Did Not Receive ECT35 No Clinical Outcome Evaluation19 Unable to Contact14 Refused PostECT Evaluation2 Untestable Due to Cognitive Impairment
Intent-to-Treat Sample (N = 347)Baseline Neuropsychological Testing(N = 242-347)PostECT Neuropsychological Testing(N = 224-346)6-Months Follow-up Neuropsychological Testing(N = 202-260)Met Exclusion Criteria (N = 128)
Not Depressive Disorder (N = 46)ECT Within Past 2 Months (N = 27)Mini-Mental State Exam < 15 (N = 25)Not English or Spanish Speaking (N= 23)Previously Participated in Study (N = 7)
Potentially Eligible (N = 225)
Insufficient Time for Evaluation (N = 84)Refused Participation (N = 74)Physical Limitations (N = 45)Attending Requested Non-participation (N = 14)Psychiatric Condition Precluded Evaluation (N =5)Other Factors (N = 3)
Figure 1
Participant flow.
Cognitive effects of ECT
HA Sackeim
et al
and provided informed consent after study procedures hadbeen fully explained.
Study Measures
The primary instrument to assess severity of depressivesymptoms was the Hamilton Rating Scale for Depression(HRSD, 24-item) (Hamilton, 1967). Comorbid DSM-IVpsychiatric Axis I disorders, including substance abuse ordependence, were determined using a full SCID-I/P inter-view (First
et al 
, 1996a). Medical comorbidity was assessedwith the Cumulative Illness Rating Scale (CIRS) (Miller
et al 
,1992). At pre-ECT baseline, the North American AdultReading Test (NAART) provided an estimate of premorbidintelligence (Johnstone
et al 
, 1996).An extensive neuropsychological battery was adminis-tered at pre-ECT baseline, within days of completing theECT course, and at 6-month (24-week) follow-up. Adescription of the battery and the derived outcomemeasures are presented in Table 1. The modified Mini-Mental State exam (mMMS) (Stern
et al 
, 1987), a measure of global cognitive status and an expanded version (range 0–57) of the original MMS (Folstein
et al 
, 1975), has shownsensitivity to variation in ECT technique (Sackeim
et al 
,1993, 2000). Psychomotor function was assessed with threemeasures of reaction time (RT): Simple (SRT) (Benton,1977), Choice (CRT) (Benton and Blackburn, 1957), andStroop RT (MacLeod, 1991). In each task, median RT forcorrect response was determined. Although psychomotorfunction is of practical importance with respect to drivingand other motor activities, the impact of ECT on thisdomain has rarely been examined (Calev 
et a
, 1995;Sackeim, 1992). Attention was assessed with the Stroop(MacLeod, 1991) and the Continuous Performance Test(CPT) (Ballard, 1997; Cornblatt
et al 
, 1984). In severedepression, attention is often impaired, but believed toimprove with symptomatic remission (Sternberg and Jarvik,1976; Zakzanis
et al 
, 1998). However, there is virtually no information on the effects of ECT on these classicattentional measures.Anterograde and retrograde amnesia are the two deficitsmost characteristic of ECT. Anterograde learning andmemory were assessed with the Complex Figure Test(CFT) (Rey, 1941; Spreen and Strauss, 1998) and theBuschke Selective Reminding Test (BSRT) (Buschke, 1973;Hannay and Levin, 1985). Deficits in delayed recall on theBSRT have been repeatedly documented shortly followingECT, and found to be sensitive to variation in the treatmenttechnique (Sackeim
et a
, 1993; Sackeim
et a
, 2000).Retrograde amnesia for autobiographical information wasmeasured with the Columbia University AutobiographicalMemory Interview-Short Form (AMI-SF) (McElhiney 
et al 
,1997, 1995). The original version of the AMI, containing 281items, has shown strong reliability and validity as a measure
Table 1
Neuropsychological Battery 
TestMethod of administration Outcome measureTask order 
Global cognitive status
Modified Mini Mental State Exam (mMMS) Paper-and-pencil Total score (maximum
57) 1
Psychomotor function
Simple Reaction Time (SRT) Computerized Median reaction time on 60 trials 4Choice Reaction Time (CRT) Computerized Median reaction time on correct trials (maximum trials
60)5Stroop Reaction Time (Stroop RT) Computerized Median reaction time on correct trials on the StroopTest (maximum trials
Stroop Color-Word Interference (Stroop effect) Computerized Interference Score: Ratio of RT on color-word conflict trials (
90) to color trials (
45)8Continuous Performance Test (CPT) Computerized Sensitivity (
) in detecting consecutive and identicalfour digit targets (150 trials; 28 targets)6
 Anterograde learning and memory 
Complex figure test (CFT) Paper-and-pencil (1) Copying of complex figure 3(2) Reproduction of complex figure after a 20mindelay 9Buschke Selective Reminding Test (BSRT) Paper-and-pencil (1) Total recall of a list of 12 unrelated words on 6 trials 2(2) Free recall of the 12 words after a 30min delay 7
 Autobiographical memory 
Autobiographical Memory Interview-Short Form(AMI-SF)Paper-and-pencil Consistency of report with baseline answers for 30questions about 5 autobiographical events10
Cognitive effects of ECT
HA Sackeim
et al

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