Addressing Psychiatric Comorbidities in Patients With Epilepsy

Persons with epilepsy have a high incidence of psychiatric comorbidities, and these comorbidities have a direct effect on treatment outcome, according to Andres Kanner, MD, professor of neurological sciences,senior attending physician in neurology, and director of the Laboratory of Electro- encephalography and Video-EEG- Telemetry at Rush University Medical Center in Chicago. In a presentation given this past June during the midyear meeting of the American Epilepsy Society in Oak Brook, Illinois, Kanner cited studies from the literature showing that the rates of depression, anxiety, psychosis, and attention-deficit/ hyperactivity disorder (ADHD) are significantly higher among persons with epilepsy than among the general population (Table).^1-5 Kanner provided a strong argument that epilepsy and depression, in particular, are closely tied and that effective treatment of the epilepsy is often contingent on appropriate identification and treatment of the psychiatric comorbidity as well.

"Psychiatric disorders are having a direct effect on treatment of seizures," he contended. "Not only is severe epilepsy associated with a higher risk of depression, but we are now asking whether depression may be a biologic marker for severe epilepsy," he said.

A study by Kanner and colleagues at Rush confirmed published findings suggesting that epilepsy and depression often go hand in hand. They found a history of psychiatric comorbidity in 49 (54%) of 90 patients who underwent surgery (temporal lobe resections) for seizure control. Major depression was the most common psychiatric disorder, affecting 84% of patients who had a history of psychiatric intervention. Of crucial import was that, among the 90 patients who underwent surgery for management of epilepsy, postoperative transient seizures occurred in twice as many patients who had a history of depression as patients who lacked such a history. Furthermore, disabling postoperative seizures were more than twice as likely to occur in patients with depression as in patients without depression (51% vs 22%).

Proper treatment of epilepsy in patients with comorbid psychiatric conditions requires identification of the psychiatric disorder and either treating it or referring the patient to a mental health specialist, Kanner said. SSRIs are the first choice for depression, followed by serotonin-norepinephrine reuptake inhibitors (SNRIs). Kanner strongly urged neurologists to rule out bipolar disorder (BPD) in seemingly depressed patients and equally urged neurologists to refer, rather than troubleshoot, patients suspected of having BPD, patients who are suicidal, and patients who do not respond to second-line (ie, SNRI) therapy.

Kanner noted that SSRIs are safe in patients with epilepsy, but the agents should not be discontinued abruptly to avoid a flare of depression. He also cautioned that, although monoamine oxidase inhibitors are classic antidepressants, "they are drugs that neurologists should not be using. Dispensing of such agents should be left to psychiatrists."

To allay fears that antidepressants might trigger seizures, Kanner related data from placebo-controlled trials showing that seizure episodes were much more likely to occur among patients receiving placebo than an antidepressant (535 seizure episodes per 100,000 years among patients receiving antidepressants, compared with 1502 seizure episodes per 100,000 years among patients receiving placebo). However, certain agents should be avoided in patients with epilepsy, including maprotiline(Drug information on maprotiline) (Ludiomil), bupropion (Wellbutrin, Zyban), and clomipramine(Drug information on clomipramine) (Anafranil).

He reminded the audience that depression and anxiety disorders often coexist. "SSRIs are very effective," he said, although no studies have looked into their use for treating anxiety in patients with epilepsy. Although benzodiazepines and SNRIs might be other therapeutic choices, they may cause additive toxicities when given with certain antiepileptic drugs.