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Longer seizures during the first electroconvulsive therapy (ECT) session was linked with a greater likelihood of remission in major depressive disorder, a population-based cohort study suggested.

In an adjusted model, patients who had an initial seizure duration of at least 30 seconds had a twofold higher odds of remission compared with patients with seizure duration of less than 20 seconds, Axel Nordenskjöld, MD, PhD, of Örebro University Hospital in Sweden, and colleagues reported in .

"To our knowledge, this cohort study is the largest yet supporting the association between seizure length and remission from MDD [major depressive disorder] after ECT. Seizure duration appeared to be indicative of adequate treatment quality," the authors wrote.

Out of the nearly 7,000 patients with depression who underwent ECT, 39.3% achieved remission within 1 week after therapy.

While the aim of -- a treatment only for severe cases of depression -- is to induce a therapeutic seizure, the most efficacious seizure duration has long been in question. While anything under 20 seconds is typically considered inadequate for a therapeutic response, anything exceeding 120 to 180 seconds is linked with a higher risk for adverse events.

Those who had a 60- to 69-second seizure had the highest odds of remission, but any seizure length of 20 seconds or longer was significantly associated with a higher odds of remission compared with a seizure lasting less than 20 seconds:

• 20-29 seconds: aOR 1.56 (95% CI 1.16-2.09)
• 30-39 seconds: aOR 2.09 (95% CI 1.58-2.77)
• 40-49 seconds: aOR 2.23 (95% CI 1.69-2.95)
• 50-59 seconds: aOR 2.45 (95% CI 1.85-3.25)
• 60-69 seconds: aOR 2.52 (95% CI 1.88-3.39)
• ≥70 seconds: aOR 2.45 (95% CI 1.84-3.28)

However, author James Luccarelli, MD, DPhil, of Massachusetts General Hospital in Boston, called for caution when extrapolating these findings, warning these models were only based off the duration of the patients' initial seizure -- not the overall ECT course.

For reference, median number of sessions was seven for those who achieved remission and eight for those who did not.

"[E]ven among those with initial seizures of less than 20 seconds the remission rate from depression was 27.2%, which is much greater than that obtained by pharmacotherapy in patients with treatment resistance," he pointed out. Because of this, Luccarelli said a short seizure during the initial treatment isn't a reason to discontinue ECT in patients who are indicated for it.

"[I]n many ways the first ECT treatment, particularly for right unilateral electrode placement as used in this study, is unlike subsequent treatments," Luccarelli wrote, explaining that in most cases, the first seizure is mostly used to find the patients' individual seizure threshold and subsequent treatments can be delivered "at a multiple (sixfold or greater) of this initial threshold."

Nordenskjöld's group pinpointed a few other factors that impacted ECT-induced seizure duration. Patients who were on anticonvulsant medications tended to have shorter seizure durations and lower remission rates.

Odds of depression remission after ECT for patients on the following concurrent pharmacological treatments were significantly lower:

• Lamotrigine (Lamictal): aOR 0.67 (95% CI 0.53-0.84)
• Benzodiazepines: aOR 0.76 (95% CI 0.69-0.84)
• Other anticonvulsants: aOR 0.53 (95% CI 0.42-0.66)

"It seems reasonable that anticonvulsants are unfavorable when a convulsion is the aim, but it is nevertheless common clinical practice to combine an anticonvulsant and ECT," Nordenskjöld explained to 麻豆传媒. "Be cautious [when combining] anticonvulsants and ECT for the treatment of depression in patients without epilepsy."

Luccarelli commented that this was "the most actionable finding for ECT practitioners," and added that while these findings could be confounded by indication, "cautious tapering of these medications prior to ECT may enhance treatment outcome."

Use of antidepressants, lithium, and antipsychotics did not have a significant association with remission rates.

But treatment outcomes were not always associated with longer seizure duration. A higher electrical charge was linked with a significantly shorter seizure duration (β coefficient -3.32, P<0.001), but also with higher remission rates (aOR 1.15, 95% CI 1.04-1.28).

Anesthetic agents and doses were also linked with variable remission outcomes, as use of thiopental was associated with longer seizure duration but lower remission rates compared with propofol's seizure duration (β coefficient 2.49, P<0.001) and remission (aOR 0.87, 95% CI 0.79-0.97).

In addition, a higher anesthetic dose was tied with lower remission rates (aOR 0.84, 95% CI 0.76-0.94) than a low dose, and Nordenskjöld advised clinicians not to use more propofol or thiopental than needed to sedate patients.

And age was a factor here as well. "Old patients tend to have short seizures, but still tend to have greater symptom relief than young patients with long seizures," Nordenskjöld added.

Data for the study was pulled from the Swedish National Quality Register for ECT. Patients included in the analysis were treated at Swedish hospitals for unipolar MDD with unilateral electrode placement from January 2012 through December 2019. The average age was 55 and 60% were female.

The anesthetic agents used were propofol (1-1.5 mg/kg) or thiopental (2-4 mg/kg), and the muscle relaxant used was succinylcholine (0.5-1 mg/kg). Pulse amplitude, frequency, duration, and charge were personalized to the patient. Remission was based on Montgomery-Åsberg Depression Rating Scale (MADRS-S) within 1 week after the last treatment session.

Limitations of the study included the uncertainty of whether the association between seizure length and treatment outcome is causal and the possible confounding of length of antidepressant treatment. In addition, other factors, such as seizure intensity or seizure generalization, may play a role in the antidepressant properties of ECT. This study also investigated only patients treated with unilateral electrode placement, so results with bitemporal electrode placement need to be confirmed.

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