Despite widespread clinical evidence of the effectiveness of
electroconvulsive therapy (ECT), the view persists that cognitive side effects
such as amnesia indicate structural brain damage, although the literature
fails to substantiate this. Now a small but rigorously designed study
contradicts this view. After administering high-dosage ECT to nonhuman
primates under essentially clinical conditions, a team of investigators at New
York State Psychiatric Institute and Columbia University report no visible
evidence of neuropathological lesions in serial sections of brain tissue.
"This is important for psychiatrists to know because if they
recommend that a very depressed patient have ECT, and the patient is fearful
that the procedure will cause brain damage, they can reassure them that the
latest neuropathological study shows that ECT does not cause brain
damage," Andrew Dwork, M.D., the neuropathologist who examined the
frozen sections of brain tissue, told Psychiatric News.
The NIMH-funded study is also the first to compare the safety of the new
convulsive treatment magnetic seizure therapy (MST) with ECT, said principal
investigator Sarah H. Lisanby, M.D., of the magnetic stimulation laboratory in
the department of biological psychiatry at the New York State Psychiatric
Institute. She is also an associate professor of psychiatry at Columbia
University College of Physicians and Surgeons (see article above).
In the March American Journal of Psychiatry, the investigators
noted how flaws in previous studies of ECT, such as confounding variables,
invalidated the findings. To avoid such pitfalls, their study was designed to
mimic clinical conditions more closely than ever before: giving the animals
general anesthesia, muscle relaxants, and oxygen and then monitoring them for
seizures and physiological changes.
Twelve Macaca mulatta monkeys divided into groups of three and matched for
age, weight, and sex were each given ECT, MST, or a sham treatment. All staff
not involved in the interventions were masked to group assignment.
Bilateral ECT was administered at 2.5 times an individual monkey's seizure
threshold, approximating high doses of bilateral ECT given to patients. MST
was given using a repetitive stimulator with enhanced output. Sham
interventions were identical without brain stimulation.
Interventions were given four days per week for six weeks. To provide
greater sensitivity to the detection of any damage, both chronic and acute
effects of treatment were sought. To allow development of any chronic
neuropathologic effects, there was a five-week recovery period before the last
intervention. To detect any acute brain changes, animals were euthanized three
days after the last intervention.
To prevent artifacts from being introduced during their handling, brains
were perfused with formalin before removal.
Frozen 40-micron sections of the left hemisphere from the amygdala through
the hippocampus and the brain stem were processed with a variety of stains.
Dwork examined all sections, which were masked to intervention.
None of the ECT-treated monkeys showed pathological findings. Some
neurological changes in one animal given MST were consistent with hypoxia but
were too acute to be linked to MST or anesthesia.
The investigators said that the study group was too small for them to
detect subtle, quantitative changes such as a smaller number of neurons or a
larger number of microglial cells. This is a limitation of terminal primate
studies. They are now counting neurons in twice the number of animals to find
whether there are subtle changes in various areas of the brain after ECT.
In addition, although animal studies cannot reveal the comprehensive
effects of a lifetime of treatment and illness, primates are the closest
possible models for examining the direct impact of interventions on the human
brain. The investigators ruled out an examiner-based rating bias resulting in
Regardless of its limitations, "this a very reassuring study because
we have been proceeding on principle that ECT did not cause any structural
brain damage," said Mark George, M.D., an associate professor of
psychiatry, radiology, and neurology and director of the function imaging
division in psychiatry at the Medical University of South Carolina in
That was based on work done almost 20 years ago. Recently investigators
failed to find any structural changes in the brain when they compared MRI
scans taken before and after ECT, he added.
The study, "Absence of Histological Lesions in Primate Models
of ECT and Magnetic Seizure Therapy," is posted online at<http://ajp.psychiatryonline.org/cgi/content/full/161/3/576?>.▪
Am J Psychiatry2004161576