HOUSTON—Treating psychiatric symptoms in patients with refractory epilepsy is likely to improve the overall course of the disease, as well as patients’ quality of life, according to an overview provided at the 70th Annual Meeting of the American Epilepsy Society.
Jay Salpekar, MD
Epilepsy “is not necessarily a neurologic disease with psychiatric comorbidity. Maybe there is something in the interface … that is really our target,” he said.
Epilepsy and psychiatry have considerable symptom overlap, Dr. Salpekar noted. For example, someone with a seizure focus in the amygdala might have an aura of anxiety or overwhelming fear that resembles the early stages of a panic attack.
Neurologists should aim to treat seizures and psychiatric symptoms. “Think about psychiatric symptoms as clues that we have not treated the entire disease yet,” Dr. Salpekar said. “We want to use our anticonvulsants to treat the entire disease, and maybe that will lead to improved seizure control.”
A Bidirectional Relationship
Understanding the bidirectional relationship between neuropsychiatric disorders and epilepsy is key to treatment. “Not only are you more likely to be depressed if you have epilepsy, but you are more likely to have epilepsy or develop seizures if you are depressed,” Dr. Salpekar said. This finding represents “a paradigm shift … in how we interpret what this illness could be.”
In addition, ADHD increases the likelihood of seizures, and one study found that 28% of children with ADHD who underwent polysomnography had centrotemporal spikes. Other research suggests that patients with epilepsy may have structural changes and cognitive symptoms prior to their first identified seizures.
Antiepileptic drugs (AEDs) effectively treat psychiatric symptoms, including impulsivity, rage outbursts, and mood lability. “In the psychiatric world, we depend upon these [drugs] all the time,” Dr. Salpekar said. “Maybe there are relationships between seizure control and behavior control that are more clear-cut than we have thought.”
Treatment Options
Dr. Salpekar and colleagues in 2006 conducted a review of patients with epilepsy and comorbid bipolar spectrum disorder. They reviewed cases to see whether treatment with AEDs improved bipolar symptoms, such as mood lability, impulsivity, rage outbursts, and extreme irritability, as well as seizures. They found that carbamazepine, divalproex sodium, lamotrigine, and oxcarbazepine monotherapies were associated with better psychiatric symptom ratings, compared with other monotherapies. In many cases, the drugs appeared to treat epilepsy and mood disorder simultaneously. The findings suggest that AEDs can “bridge the gap between epilepsy or seizure counts and psychiatric symptoms” and that neurologists should “aim for broad-spectrum treatment,” he said.
Psychiatric symptoms sometimes may be related to AEDs. If an AED causes depressive symptoms or irritability, neurologists should try to remove it. In addition, benzodiazepine withdrawal may cause depression, and this effect may occur in certain patients due to their metabolism. “If someone is a fast metabolizer, and they are taking b.i.d. clonazepam, what happens if it wears off?” In those cases, behavior problems may occur late in the afternoon when serum drug concentrations are lowest.
Many GABAergic drugs have been reported to improve anxiety. Gabapentin also has been reported to improve social phobia and chronic pain. Potential negative effects of GABAergic drugs include depression, sedation, mood lability, and hyperactivity.
Among antiglutamatergic drugs, lamotrigine may be the best evidence-based option for improving mood or depression. Lamotrigine, however, may promote mania in patients with a propensity for bipolar spectrum disorder.
Among drugs with other mechanisms of action, carbamazepine is known to be a mood stabilizer, and eslicarbazepine may have the same effect. Levetiracetam may cause irritability, but the drug also may improve mood in some cases. “There are positives and negatives with any of our AEDs,” Dr. Salpekar said.
An Important Question to Ask Patients
Patients with severe refractory epilepsy often have depression, and treating depression may improve their quality of life dramatically. “When all else fails, at the very least, we want to identify if depression is present because we can do something about that most of the time,” Dr. Salpekar said.
Many depression screening tools are available, but the important thing is to broach the subject. “I would encourage all of you to ask one question of your patients. Just say, ‘Are you depressed?’ That might be all you have to do.”
Depression may be more common in patients with temporal lobe foci, and evidence suggests that adults with left foci have an increased likelihood of depression. Waxman and Geschwind observed that patients with temporal lobe epilepsy may have an increased preoccupation with philosophical, moral, or religious issues, which also can be characteristic of manic episodes, Dr. Salpekar said.
Dr. Salpekar and colleagues conducted a study of children with medically refractory epilepsy who presented for surgical evaluation to assess whether psychiatric symptoms differed according to seizure focus. Researchers reviewed case records for 40 patients. Patients with suspected temporal lobe foci had more behavioral problems and were more likely to have a diagnosis of depression, compared with children with extratemporal foci. This finding “lends some credence to our idea that temporal lobe foci are worse … in terms of depression,” he said.
Treating Depression
Neurologists can follow practical steps to address depression. First, determine whether symptoms are attributable to drug side effects. Then, address lifestyle factors, including sleep, exercise, and diet, and consider social stressors, such as family members or employers who do not appreciate the patient’s cognitive or physical limitations. Neurologists should identify targets that help measure whether treatment is working and consider whether low doses of adjunctive AEDs may help treat psychiatric symptoms. Finally, neurologists may consider prescribing an antidepressant. “If you are going to use an antidepressant, get comfortable, skilled, and knowledgeable about using one of them,” he said.
Studies have provided data regarding the use of antidepressants in patients with epilepsy. In an observational pediatric study, 36 patients who received fluoxetine or sertraline improved clinically, whereas two patients who received fluoxetine or sertraline had worsened seizures. Studies also have provided evidence for the use of citalopram and sertraline in adults with epilepsy. Other studies regarding the treatment of depression in epilepsy are ongoing.
Selective serotonin reuptake inhibitors (SSRIs) entail a low risk of lowering seizure threshold, as do certain antipsychotics (eg, haloperidol, risperidone, and aripiprazole). Methylphenidate is considered safe and is widely used for children with epilepsy and comorbid ADHD.
Nonmedical treatment also can benefit patients. Social skills groups, overnight camps, and cognitive behavioral therapy may be effective options. Vocational support also is important. “Meaningful activity can … tip the balance into more functionality,” he said. “Think about seizure control and behavior control as partners,” Dr. Salpekar concluded. “Think about treating both of these types of targets as working together to improve the entire illness.”
—Jake Remaly
Suggested Reading
Hermann BP, Dabbs K, Becker T, et al. Brain development in children with new onset epilepsy: a prospective controlled cohort investigation. Epilepsia. 2010;51(10):2038-2046.
Hesdorffer DC, Hauser WA, Olafsson E, et al. Depression and suicide attempt as risk factors for incident unprovoked seizures. Ann Neurol. 2006;59(1):35-41.
Salpekar JA. Mood disorders in epilepsy. Focus. 2016;14(4):465-472.
Salpekar JA, Berl MM, Havens K, et al. Psychiatric symptoms in children prior to epilepsy surgery differ according to suspected seizure focus. Epilepsia. 2013;54(6):1074-1082.
Salpekar JA, Conry JA, Doss W, et al. Clinical experience with anticonvulsant medication in pediatric epilepsy and comorbid bipolar spectrum disorder. Epilepsy Behav. 2006;9(2):327-334.
Silvestri R, Gagliano A, Calarese T, et al. Ictal and interictal EEG abnormalities in ADHD children recorded over night by video-polysomnography. Epilepsy Res. 2007;75(2-3):130-137.
Waxman SG, Geschwind N. The interictal behavior syndrome of temporal lobe epilepsy. Arch Gen Psychiatry. 1975;32(12):1580-1586.
