Literature Review

ILAE offers first guide to treating depression in epilepsy



The International League Against Epilepsy (ILAE) has issued recommendations for treating depression in patients with epilepsy.

The new guidance highlights the high prevalence of depression among patients with epilepsy while offering the first systematic approach to treatment, reported lead author Marco Mula, MD, PhD, of Atkinson Morley Regional Neuroscience Centre at St George’s University Hospital, London, and colleagues.

“Despite evidence that depression represents a frequently encountered comorbidity [among patients with epilepsy], data on the treatment of depression in epilepsy [are] still limited and recommendations rely mostly on individual clinical experience and expertise,” the investigators wrote in Epilepsia.

Recommendations cover first-line treatment of unipolar depression in epilepsy without other psychiatric disorders.

For patients with mild depression, the guidance supports psychological intervention without pharmacologic therapy; however, if the patient wishes to use medication, has had a positive response to medication in the past, or nonpharmacologic treatments have previously failed or are unavailable, then SSRIs should be considered first-choice therapy. For moderate to severe depression, SSRIs are the first choice, according to Dr. Mula and colleagues.

“It has to be acknowledged that there is considerable debate in the psychiatric literature about the treatment of mild depression in adults,” the investigators noted. “A patient-level meta-analysis pointed out that the magnitude of benefit of antidepressant medications compared with placebo increases with severity of depression symptoms and it may be minimal or nonexistent, on average, in patients with mild or moderate symptoms.”

If a patient does not respond to first-line therapy, then venlafaxine should be considered, according to the guidance. When a patient does respond to therapy, treatment should be continued for at least 6 months, and when residual symptoms persist, treatment should be continued until resolution.

“In people with depression it is established that around two-thirds of patients do not achieve full remission with first-line treatment,” Dr. Mula and colleagues wrote. “In people with epilepsy, current data show that up to 50% of patients do not achieve full remission from depression. For this reason, augmentation strategies are often needed. They should be adopted by psychiatrists, neuropsychiatrists, or mental health professionals familiar with such therapeutic strategies.”

Beyond these key recommendations, the guidance covers a range of additional topics, including other pharmacologic options, medication discontinuation strategies, electroconvulsive therapy, light therapy, exercise training, vagus nerve stimulation, and repetitive transcranial magnetic stimulation.

Useful advice that counters common misconceptions

According to Jacqueline A. French, MD, a professor at NYU Langone Medical Center, Dr. Mula and colleagues are “top notch,” and their recommendations “hit every nail on the head.”

Jacqueline A. French, MD, a professor at NYU Langone Medical Center and chief medical officer of the Epilepsy Foundation.

Dr. Jacqueline A. French

Dr. French, chief medical officer of The Epilepsy Foundation, emphasized the importance of the publication, which addresses two common misconceptions within the medical community: First, that standard antidepressants are insufficient to treat depression in patients with epilepsy, and second, that antidepressants may trigger seizures.

“The first purpose [of the publication] is to say, yes, these antidepressants do work,” Dr. French said, “and no, they don’t worsen seizures, and you can use them safely, and they are appropriate to use.”

Dr. French explained that managing depression remains a practice gap among epileptologists and neurologists because it is a diagnosis that doesn’t traditionally fall into their purview, yet many patients with epilepsy forgo visiting their primary care providers, who more frequently diagnose and manage depression. Dr. French agreed with the guidance that epilepsy specialists should fill this gap.

“We need to at least be able to take people through their first antidepressant, even though we were not trained to be psychiatrists,” Dr. French said. “That’s part of the best care of our patients.”

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic, said the recommendations are a step forward in the field, as they are supported by clinical data, instead of just clinical experience and expertise.

Imad Najm, MD, director of the Charles Shor Epilepsy Center, Cleveland Clinic

Dr. Imad Najm

Still, Dr. Najm noted that more work is needed to stratify risk of depression in epilepsy and evaluate a possible causal relationship between epilepsy therapies and depression.

He went on to emphasizes the scale of issue at hand, and the stakes involved.

“Depression, anxiety, and psychosis affect a large number of patients with epilepsy,” Dr. Najm said. “Clinical screening and recognition of these comorbidities leads to the institution of treatment options and significant improvement in quality of life. Mental health professionals should be an integral part of any comprehensive epilepsy center.”

The investigators disclosed relationships with Esai, UCB, Elsevier, and others. Dr. French is indirectly involved with multiple pharmaceutical companies developing epilepsy drugs through her role as director of The Epilepsy Study Consortium, a nonprofit organization. Dr. Najm reported no conflicts of interest.

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