Depression, bipolar disorder, anxiety, and psychosis are all more common in patients with epilepsy. If patients have symptoms or a history of depression, antiepileptic drugs (AEDs) with adverse mood effects (topiramate, levetiracetam, zonisamide, clobazam, perampanel, and phenobarbital) should be avoided whenever possible. Medications with favorable effects on mood (“mood stabilizers”), such as carbamazepine, lamotrigine, or valproate, are preferred. Withdrawal of these mood-stabilizing AEDs may also contribute to depressive symptoms. If treatment with an antidepressant is required, selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs/SNRIs) are appropriate and safe. Clomipramine, maprotiline, amoxapine, and bupropion should be avoided due to risk of lowering the seizure threshold.
Anxiety is a common comorbid condition in patients with epilepsy. Symptoms of anxiety and panic may represent a seizure aura, and should be distinguished from a primary psychiatric cause. If the latter, SSRIs/SNRIs are a reasonable initial treatment options; long-term benzodiazepine use should be limited.
Psychosis occurs in 5%–10% of patients with epilepsy, most often in those with temporal lobe epilepsy. Psychosis in a patient with epilepsy may represent AED side effects, ictal or postictal psychosis, or a primary psychiatric disorder. AED changes should be made if appropriate. If psychosis is thought to be ictal or postictal, evaluation in an epilepsy-monitoring unit may be needed; in these cases improved seizure control is usually the best approach to limit recurrent episodes of psychosis. Postictal psychosis may require both improved seizure control as well as use of antipsychotic agents for acute symptom control during episodes. With the possible exception of ictal psychosis, treatment by a psychiatrist is needed, and initiation of antipsychotic medication is usually recommended. Use of some antipsychotics, particularly clozapine, should be limited due to risk for lowering seizure threshold.
Cognitive impairment is common in epilepsy, and can vary from subtle deficits to severe intellectual disability. Epilepsy-specific causes may include underlying disease, medication side effect, or increased duration or frequency of seizures. Ambulatory electroencephalogram may be needed for evaluation if increased seizure burden (including subclinical seizures) is suspected. If this is excluded, AEDs should be optimized. Among common AEDs, topiramate typically causes the most notable cognitive impairment, particularly at high dose or with rapid titration. Other potential contributing AEDs include zonisamide, phenobarbital, and benzodiazepines.
Obstructive sleep apnea (OSA) can be associated with increased seizure frequency. Use of AEDs that lead to weight loss, such as topiramate, and avoidance of those that lead to weight gain, such as valproate, may help decrease the severity of OSA. Of note, vagus nerve stimulation (VNS) has been shown to exacerbate sleep apnea, and sleep specialist consultation should be considered prior to VNS implantation if sleep apnea is present or suspected. Insomnia can be a side effect of AEDs, especially felbamate and lamotrigine. In these cases, dose medications earlier in the evening. AEDs with more sedating properties can be given with a higher dose in the evening than in the morning; this is especially valuable if seizures are primarily nocturnal. Use of extended-release formulations can help with both daytime fatigue and, with lamotrigine, insomnia. This can be done either using twice-daily dosing (to limit the effect of postdose peak) or once-daily dosing, typically given in the evening for potentially sedating medications. Similarly, medications given once daily, such as perampanel or zonisamide, should usually be given in the evening rather than the morning. Improved sleep hygiene, trial of melatonin, or referral to a sleep specialist should also be considered if AED adjustment fails to improve insomnia.
Headaches and epilepsy often coexist. Lamotrigine may trigger or exacerbate headache. Valproate, topiramate, and zonisamide generally improve headaches. Other common treatments for primary headaches, such as nortriptyline and propranolol, are reasonable once secondary causes of headache have been excluded.