Managing psychiatric illness in patients with epilepsy

Patients who have epilepsy have a higher incidence of psychi­atric illness than the general population—at a prevalence of 60%.¹ Establishing a temporal association and making a psy­chiatric diagnosis can be vexing, but awareness of potential comorbidi­ties does improve the clinical outcome² (Box). As this article discusses, psychiatric presentations and ictal disorders can share com­mon pathology and exacerbate one another.³ Their coexistence often results in frequent hospitalization, higher treatment cost, and drug-resistant seizures.⁴ Risk factors for psychopathology in people who have epilepsy include psychosocial stressors, genetic factors, early age of onset of seizures, and each ictal event.⁵ Among ictal disorders, tem­poral-lobe epilepsy confers the highest rate of comorbidity.³

Mood disorders
Mood disorders are the most common psychiatric disorder comorbid with epilepsy (irrespective of age, socioeconomic status, and ethnic­ity), affecting 43% of patients who have a seizure disorder.⁵ These disorders present as an ictal aura in 1% of cases; the presence of a comorbid mood disorder implies a more severe form of epilepsy.² Most mood disorders are underdiagnosed in epilepsy, however, because of the mistaken assumption that depression is a normal reaction to hav­ing a seizure disorder.

Interictal depression is the most commonly reported complaint, although dysphoria also can present peri-ictally.6 The severity of depression and the seizure disorder often are directly proportional to each other.1 Decreased levels of serotonin and norepinephrine, or abnormalities in their transport or post­synaptic binding, have been reported in epilepsy and in affective illness.6 MRI studies have documented that patients who have a depressive disorder have more gray-matter loss compared with healthy controls.7 Depression diminishes the qual­ity of seizure remission after medical and surgical interventions for epilepsy.8

Taking a multidisciplinary approach to treating a mood disorder in a patient who has epilepsy might improve ictal and mood outcomes.⁹ Anhedonia is the most common presenting symptom, but some patients do not meet DSM-5 criteria. Depression exhib­its atypically, with fatigue, irritability, poor frustration tolerance, anxiety, and mood lability.⁶ Self-report screening scales, such as the Neurological Disorders Depression Inventory for Epilepsy, are helpful for mak­ing a diagnosis.¹⁰

Treatment. Prompt antidepressant treat­ment is indicated. Selective serotonin reuptake inhibitors (SSRIs) and sero­tonin-norepinephrine reuptake inhibitors are the most common agents in this set­ting.¹¹ Consider possible cytochrome P450 interactions between antiepileptic drugs (AEDs) and antidepressants; sertra­line, citalopram, and escitalopram have the lowest incidence of adverse effects. Because tricyclic antidepressants have proconvulsant properties, they are not commonly prescribed in these patients¹² (Table 1).¹³

Electroconvulsive therapy and vagus nerve stimulation¹⁴ are effective interven­tions in treatment-resistant depression. The efficacy of transcranial magnetic stimula­tion remains to be clarified.

AEDs can produce psychiatric effects, even in nonconvulsive epilepsies. Twenty-eight percent of cases of depression that are comorbid with epilepsy have an iatro­genic basis, and can be induced by barbi­turates, topiramate, vigabatrin, tiagabine, and levetiracetam.¹³ These adverse effects are a common reason that patients discon­tinue drug treatment and obtain psychiatric consultation.¹⁵

Neurosurgical management of epilepsy carries a low risk of depression compared with pharmacotherapy because the surgery offers better ictal control.¹⁶ Because some AEDs have mood-stabilizing properties, discontinuing one might unmask an under­lying mood disorder.¹⁷

The incidence of adjustment disorder with depressed mood in persons who have epilepsy is 10%; with dysthymia, the inci­dence is 4%. Adjustment problems with an adverse psychosocial outcome are docu­mented more often in patients who have a long-standing, chronic disorder than in those with a more recent diagnosis.¹⁸

Postictal suicidal ideation is more com­mon in persons who have a preexisting mood disorder.⁶ The rate of suicide among epilepsy patients is 5%, compared with 1.4% in the general population—which is the same rate seen among patients with other psychiatric conditions, but higher than what is observed in many chronic medical conditions.¹⁹ Attempted suicide is not a direct result of epilepsy, but is sig­nificantly related to underlying psychopa­thology²⁰; anxiety comorbid with a mood disorder increases the risk of suicide.²¹

The incidence of bipolar disorder among epilepsy patients is 1.4%.²² Although some AEDs can induce mania and hypomania, valproate and lamotrigine each have mood-stabilizing properties that might prevent such episodes.²³

Anxiety disorders
Anxiety. Approximately one-third of epi­lepsy patients report anxiety. In contrast to what is seen with depression, AEDs do no alleviate anxiety.^16,19 Anxiety or fear is the most common ictal-related psychiatric symptom2 making it difficult to differenti­ate anxiety and a seizure.²⁴

Antidepressants, especially an SSRI, often are the treatment of choice; patients must be warned about the risk of an exac­erbation of anxiety precipitated by an anti­depressant. Such an adverse reaction might prompt cognitive-behavioral therapy (CBT) or limited use of a benzodiazepine.²⁵

Obsessive-compulsive disorder. The incidence of OCD in epilepsy is 14% to 22%.²⁶ Damage to the orbitofrontal cor­tex or temporal lobe epilepsy surgery can induce OCD; neurotransmitters involved are serotonin, glutamate, dopamine, and γ-aminobutyric acid (GABA).²⁷ Patients may report obsessive thoughts in the peri-ictal period as well; some AEDs, such as topiramate, have been reported to induce such behaviors.²⁸ Treatment options include CBT, an antidepressant, and, in refractory cases, neurosurgery.²⁹

Psychosis
The prevalence of psychosis is approxi­mately 10% among persons who have epilepsy, and is observed most often in patients who have complex partial sei­zures.³⁰ Risk factors include a family history of epilepsy or psychosis, temporal lobe epi­lepsy, a long seizure history, and significant neuropathology.³¹ Structural abnormalities in the limbic system, especially the hippo­campus, predispose patients to psychosis. Abnormal activity of GABA and dopamine are implicated in psychotic symptoms in these patients.³²

Depending on the type and focus of the seizure, ictal psychoses present with cog­nitive and affective symptoms or halluci­nations. Delusions can be associated with comorbid traumatic brain injury.³² Postictal psychosis is differentiated from other peri-ictal confusional states by: