Past and Current Psychiatric Symptoms
“One in three people with epilepsy will at some point in their lives have [a] psychiatric disorder,” said Dr. Kanner, citing a population-based study of 36,984 subjects that compared people with and without epilepsy in Canada. The data showed that one in four people have experienced suicidal ideation or a suicide attempt, one in five had a major depressive episode, and one in five had an anxiety disorder. Epilepsy is associated with premature mortality, and patients with epilepsy and a mood or anxiety disorder have a 12- to 32-fold higher risk of committing suicide than the general population does.
Psychiatric disorders often precede the onset of epilepsy, Dr. Kanner noted, and a family psychiatric history increases the likelihood of psychiatric disorders in patients with epilepsy. He pointed out that people with epilepsy have a five- to 20-fold higher risk of depression than does the general population, and that patients with depression have a two- to threefold higher risk of epilepsy. Patients with a history of suicidality may have a fivefold higher risk of epilepsy. “Therefore, there is a bidirectional relationship between these conditions.”
Patients who had psychiatric illness before the onset of epilepsy, as well as those with recurring mood and anxiety disorders, have an increased risk that AEDs will cause negative psychiatric symptoms. Phenobarbital, levetiracetam, topiramate, zonisamide, and perampanel are some of the AEDs associated with negative psychotropic properties, said Dr. Kanner. Carbamazepine, oxcarbazepine, valproic acid, lamotrigine, gabapentin, and pregabalin have positive psychotropic properties, which can often yield a therapeutic effect in patients with these conditions.
“Mood and anxiety disorders are more frequently seen in people with temporal and frontal lobe epilepsies, although we now recognize that people with generalized epilepsy are also at increased risk,” Dr. Kanner said. A large percentage of patients with a history of mood and anxiety disorders experience a recurrence of these symptoms within three to six months after temporal lobectomies, he added.
Clinical tools that neurologists can use to identify patients with psychiatric symptoms include the Neurological Disorders Depression Inventory for Epilepsy and Generalized Anxiety Disorder-7 scales.
Timing Is Important
Many physicians recognize when a patient’s depressive or anxiety episode is an interictal phenomenon, meaning that it occurs independently of the seizure. However, they often overlook peri-ictal psychiatric symptoms, Dr. Kanner said. Peri-ictal symptoms include preictal symptoms, which precede the onset of the seizure by two to three days, with the intensity of the symptoms increasing as the seizure gets closer; ictal symptoms, in which the psychiatric symptom is the clinical manifestation of the seizure; and postictal symptoms, which typically follow the seizure within 12 hours to five days.
Interictal psychiatric symptoms respond to pharmacotherapy or cognitive behavioral therapy, Dr. Kanner explained. Ictal phenomena abate with the treatment of the seizure. Preictal and postictal psychiatric symptoms typically do not respond to psychotropic medication.
“People with interictal psychiatric phenomena often have peri-ictal psychiatric symptoms as well,” Dr. Kanner noted. “It is not simply one or the other. It can be one and the other.” He added that iatrogenic psychiatric symptoms that result from psychopharmacologic treatment or surgical treatment are often overlooked.
Quality of Life
“Multiple studies in the last two decades have shown that depression and anxiety are associated with poor quality of life,” said Dr. Kanner. “In fact, in patients with intractable focal epilepsy and comorbid mood and anxiety disorders, the frequency and severity of seizures stop driving the quality of life, and the strongest predictors of poor quality of life end up being the presence of AED toxicity and comorbid mood and anxiety disorders.”
Postictal psychiatric symptoms are also an unrecognized cause of poor quality of life. For example, the median duration of postictal psychiatric symptoms is 24 hours, Dr. Kanner pointed out. “What is worse, a seizure that lasts one to two minutes or 24 hours of thinking, ‘How am I going to kill myself?’” Cognitive behavioral therapy is a good option for postictal symptoms that do not respond to pharmacotherapy. “We teach patients that they are dealing with short-duration, time-sensitive symptoms and show them strategies to overcome them, particularly suicidal ideation.”
Panic Attack or Ictal Fear?
Symptoms of fear that patients experience as part of their epileptic seizure are often misdiagnosed as a panic disorder, Dr. Kanner said. “However, by taking a careful history, physicians can identify red flags to help distinguish between the two.”
With panic disorder, for example, consciousness is usually preserved, whereas patients with ictal fear can report confusion, difficulty focusing, or the need to take a nap after the panic episode. Also, the duration of a panic attack is at least five minutes and can last up to 20 minutes with anxiety symptoms persisting for hours, while ictal fear typically lasts less than one minute. Patients with ictal panic may salivate excessively, but people with a panic attack have a dry mouth. Patients with ictal panic rarely experience agoraphobia, but those with panic attacks do. “Furthermore, the intensity of the fear is not as strong [in ictal fear] as that of the patient with a panic attack,” Dr. Kanner noted. “The panic attack patient has a feeling of impending doom. They think they are going to die.” The two conditions are not mutually exclusive, however. Patients with ictal fear have an increased risk of panic disorder, compared with the general population.
—Adriene Marshall
Suggested Reading
Alper K, Schwartz KA, Kolts RL, Khan A. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. 2007;62(4):345-354.
Kanner AM, Barry JJ, Gilliam F, et al. Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events? Epilepsia. 2012;53(6):1104-1108.
Perucca P, Jacoby A, Marson AG, et al. Adverse antiepileptic drug effects in new-onset seizures: a case-control study. Neurology. 2011;76(3):273-279.
Tellez-Zenteno JF, Patten SB, Jetté N, et al. Psychiatric comorbidity in epilepsy: a population-based analysis. Epilepsia. 2007;48(12):2336-2344.