ECT for Mood Disorders 'Does Not Cause Dementia'

Pauline Anderson

March 16, 2018

Amid ongoing concerns that electroconvulsive therapy (ECT) may affect cognition, new research suggests the treatment does not increase dementia risk in patients, even older ones, with affective disorders.

Although ECT can cause transient memory problems, the new findings show that the treatment "does not cause dementia," author Martin Balslev Jørgensen, DMSc, professor of clinical psychiatry, Institute of Clinical Medicine, University of Copenhagen, Denmark, told Medscape Medical News.

The findings may not be all that surprising to psychiatrists who treat patients with a mood disorder, but they may give them "more authority" in talking to patients about treatment options and to those who harbor reservations about ECT, said Jørgensen.

The study was published online March 6 in Lancet Psychiatry.

Effective Treatment

ECT is an effective treatment for severe episodes of mood disorders, mainly major depression. However, memory loss is a common side effect. Although such memory loss usually resolves within weeks of treatment, it has raised concerns about ECT's potential long-term impact on cognition.

The investigators note that few studies have examined the frequency of dementia after ECT for patients with major depression. Those studies that have been conducted were limited by small sample sizes and did not include reference groups of patients with depression who did not receive ECT.

For the study, the researchers used a number of large nation-wide Danish registries. Danish personal identification numbers allowed the investigators to link individual patient data with the different registries and obtain complete follow-up information for hospital diagnosis and death.

From the Danish National Patient Registry (DNPR), the researchers analyzed data from 168,015 patients (mean age, 47.1 years) who had received a first-time hospital diagnosis of an affective disorder. Of these, 3.5% received at least one session of ECT.

A number of sources, including the DNPR, the Danish Psychiatric Central Register, and the Danish National Prescription Registry, which keeps information on acetylcholinesterase inhibitor prescriptions, provided data on incidental dementia.

In addition to the original sample, the investigators created a propensity matched score sample of 5901 patients who received ECT and of the same number who did not. This statistical approach, said Jørgensen, allowed the investigators to account for patient selection for ECT.

During a median follow-up of 4.9 years, 0.1% of patients aged 10 to 49 years developed dementia, as did 2.7% of those aged 50 to 69 years and 12.5% of those aged 70 years and older.

The rate of dementia is higher in patients with affective disorders than in persons in the general population. This may be because "all the usual suspects in aging and dementia," including fat distribution, metabolic syndrome, inflammation, and oxidative stress, are exacerbated by affective disorders, said Jørgensen.

About 3.6% of the patients in the study who were treated with ECT developed dementia, compared to 3.1% of their untreated counterparts.

In those younger than 50 years, ECT was not associated with an increase in risk for dementia compared with age-matched control persons who did not receive ECT (age-adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.67 - 3.46; P = .32). The same was true for those aged 50 to 69 years (HR, 1.15; 95% CI, 0.91 - 1.47; P = .22).

The authors note that although the overall cohort was large, analyses of younger patients lacked statistical power, mainly because of the low incidence of dementia outcomes in these age groups. Also, misdiagnosis of dementia is common in patients younger than 65 years who have depression or who abuse alcohol.

Decreased Dementia Risk

In patients aged 70 years and older, ECT was associated with a decreased rate of dementia (HR, 0.68; 95% CI, 0.58 - 0.80; P < .0001).

"When you just look at the raw data, it looks like you protect these patients from dementia, which I don't believe is the case," said Jørgensen.

Jørgensen noted that a study suggests that ECT may protect against dementia by increasing amyloid-β concentrations in the cerebrospinal fluid.

After adjusting for sex, educational level, depression subdiagnosis, and use of antidepressants and antipsychotics in the previous year, the HR in patients older than 70 years was 0.62 and remained significant, but in the propensity-score-matched analyses, the HR became nonsignificant (HR, 0.77; 95% CI, 0.59 - 1.00; P = .062).

The researchers believe this is the first study to show that ECT was associated with a decreased incidence of dementia in patients aged 70 years and older who have an affective disorder.

Clinician Fear Still an Issue

About 17.6% of the patients in the study died during follow-up (mortality rate per 1000 person-years, 35.7; 95% CI, 35.3 - 36.2). The authors note that when the competing mortality risk was taken into account, ECT did not affect mortality risk for the older patients. In the younger age groups, the HRs were greater than 1, indicating a higher incidence of dementia.

"However, these HRs were imprecisely estimated because of few outcomes, especially in patients exposed to ECT. Therefore, the results need to be verified in further studies and might need to be pooled to obtain sufficient precision of estimates for younger patients before actual recommendations can be made," the researchers state.

They investigated a sample of 13,578 men from the Danish Conscription Database who had a first-time hospital contact for an affective disorder. Of those patients, 6.8% received ECT. The conscription database contains cognitive ability scores from the men when they were 19 years old.

In this subsample of now middle-aged men, the analysis showed an increase in the incidence of dementia in those with lower premorbid cognitive ability. This could indicate that those with fewer cognitive reserves are more susceptible to the adverse cognitive effects of ECT.

However, Jørgensen stressed that the estimates were "based on a few cases of dementia and were not significant."

The authors point out that dementia diagnosis might be overestimated in patients with low cognitive ability and that symptoms of depression and reduced cognition in this subgroup might elicit both prescription for ECT and a diagnosis of dementia.

A greater percentage of the middle-aged men underwent ECT than in the overall cohort. This was possibly because they represented the age group with the highest use of ECT, said Jørgensen.

The main indication for ECT is severe psychotic depression, or severe melancholic depression, said Jørgensen. Patients with difficult-to-treat mania or those with bipolar mixed states may also benefit, he said.

For severe depression, eight to twelve ETC sessions may be recommended, he added.

Clinician fear of ECT is still a problem, as is stigmatization both within and outside the mental health profession and the misrepresentation of the therapy in popular culture. Jørgensen pointed to the 2008 Hollywood movie The Changeling, which shows ECT being used in the year 1926, more than a decade before it was invented.

Findings "Enormously Reassuring"

Commenting on the findings for Medscape Medical News, Mark George, MD, professor of psychiatry, radiology, and neurosciences and director of the Medical University of South Carolina Center for Advanced Imaging Research and the Brain Stimulation Laboratory in Charleston, said the study was "massive" and had "substantial power," making it "very important."

Determining whether having ECT at one point in life is associated with cognitive decline years later is very difficult, said George.

"Only in a really large, well-conducted study like this one can you begin to tease that apart. So it doesn't appear that treatment with ECT in any way sets the stage for later dementia."

He called the new results "enormously reassuring."

ECT, said George, is an effective, even lifesaving treatment for some patients with severe depression, although it still causes transient memory loss in some cases. But George and his colleagues are working on a new ECT approach that might eliminate this side effect.

With this new ECT technique, called focal electrically applied seizure therapy, pulsed direct current produces a very focal seizure. The current avoids the temporal lobe that affects memory and concentrates on the front of the brain to garner optimal therapeutic benefit.

So far, trial results regarding this new approach are "quite promising" with respect to preserving memory and successfully treating depression, said George.

He agreed that ECT has "a pretty bad historical reputation," which is "carried forward" today.

"But let's not let the sins of our mothers and fathers stop us from doing appropriate good care now," he said.

Cultural Context Critical

In an accompanying editorial, the editors of Lancet Psychiatry note that the cultural context surrounding the use of ECT is essential to understanding the significance of the new study.

ECT was introduced 80 years ago at a time of "therapeutic desperation." Adverse events were dismissed, patients' voices were ignored, and the treatment was overused, the editors note.

By 1975, the year the film One Flew Over the Cuckoo ' s Nest was released, ECT "had gone, in a little less than 40 years, from a symbol of a futuristic, humane, and efficient form of psychiatry to a shorthand for sadistic authoritarianism."

The editorialists note that today, ECT is almost exclusively restricted to the treatment of patients with mood disorders. It is used with anesthetic and muscle relaxants to avoid distress and injury, and strict legal and ethical frameworks govern its use.

"But, similar to psychiatrists 80 years ago, doctors today find themselves with few therapeutic options, and a great deal of anxiety. What are the side-effects of ECT, and are they really outweighed by the benefits?"

Although it's reassuring that the study found no association between ECT and dementia, "it would be naive to expect that this will lead to the treatment being enthusiastically embraced by all," the editorialists write.

"Objections to ECT go back decades, and are very understandable in view of the treatment's history, but they must be engaged with rather than simply dismissed; data are necessary but not sufficient to this process," the editorialists write.

"Even if a knowledge history will not help psychiatry avoid repeating its mistakes, it will, at least, prompt individuals to ask hard questions about authority, evidence, and the rights of patients," they conclude.

Dr Jørgensen has disclosed no relevant financial relationships. Dr George has partnered with MECTA Corporation to develop a new ECT device.

Lancet Psychiatry. Published online March 6, 2018. Abstract, Editorial

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