How seizure disorders change depression treatment
Suicide risk is high in depressed patients with epilepsy, especially the temporal lobe form.
Depression associated with epilepsy has distinct features. Blumer7 coined the term interictal dysphoric disorder (IDD), characterized by these types of symptoms:
- somatoform (anergia, pain, and insomnia)
- affective (irritability, euphoric moods, fear, and anxiety).
Is it bipolar depression? Determine if your patient’s depression might be part of a bipolar disorder. This diagnosis may modify your treatment plan because antidepressants could trigger a manic or hypomanic episode. Also look for untreated psychotic features, which are associated with a suicide completion rate of 19% in bipolar epilepsy patients.6
Screen for suicidal behavior. Ask about suicidal ideation, plans, and attempts within the past month and in the patient’s lifetime.4 Compared with the general population, the risk of suicide is 4 to 5 times higher in depressed persons with epilepsy8 and 25 times higher in those with TLE (Table 1).9 Overdoses are used in 80% to 90% of suicide attempts among patients with epilepsy, perhaps because of the availability of AEDs.3
Perceived social stigma, inability to drive, AEDs’ effects on cognition, and interpersonal and psychosocial issues may contribute to the patient’s depression. Ask about social support, recent stressful events, and financial and vocational impact of the seizure disorder.6
Table 1
Risk factors for suicide among epilepsy patients
| Age 25 to 49 years |
| Male gender |
| Coexisting psychopathology, including personality disorders |
| Temporal lobe epilepsy |
| Personal difficulties such as social or workrelated problems |
| Prolonged duration of epilepsy |
| Poor seizure control |
| Source: Reference 3 |
CASE CONTINUED: Searching for a cause
Previously Ms. A worked steadily and led an active life. She does not have a history of mania or hypomania. She is alert, neat, and cooperative. She sits calmly, gestures appropriately when speaking, and has no abnormal movements. She is subdued but says she is a bit anxious.
Her workup includes routine hematologic and biochemical parameters, EEG, and brain MRI. All are negative.
Her episodes are sudden, brief, and involve altered awareness followed by amnesia. She describes déjà vu, perceptual changes, and motor speech problems.
Ms. A’s behavioral syndrome is consistent with complex partial seizure with frontal and temporal foci. Her dominant brain hemisphere likely is involved because speech is affected. We classify her depression as postictal because of the temporal relationship with the seizures. Thus, controlling the seizures should prevent the depression.
Depression as a side effect
Depression in epilepsy is multifactorial, and pharmacotherapy is one of many biologic and psychosocial risk factors.
AED’s negative effects such as depression and cognitive changes may be caused by polypharmacy, drug- induced folate deficiency, drug titration and dosage, or withdrawal.6 Patients receiving combination therapies are more likely to be depressed.4 AED polypharmacy might be a marker for refractory epilepsy, and thus depression can be caused by both the neurologic illness and its treatment. Shorvon et al10 reported improved alertness, concentration, drive, mood, and sociability after patients’ polytherapy was reduced to monotherapy, especially carbamazepine monotherapy.
Onset or worsening of depression could coincide with starting a new AED.6 Phenobarbital and topiramate are most closely associated with acute depression during initial treatment.3 One study noted that depressed patients taking barbiturates as part of polytherapy were significantly more depressed than those taking carbamazepine.8 Phenobarbital can produce depression, suicidal ideation, and suicidal and parasuicidal behavior.
Patients starting tiagabine might develop agitation, withdrawal, and mood disturbance that could suggest depression.3 With topiramate the rate of affective symptoms is dose-dependent, with an incidence of 9% with 200 mg/d and 19% with 1,000 mg/d.11
Some patients (11% to 15%) receiving polytherapy that includes liver enzyme -inducing AEDs (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate) present with decreased serum, erythrocyte, and cerebrospinal fluid folate levels, which is associated with depression.4
Bipolar depression. AEDs such as carbamazepine, valproic acid, and lamotrigine are used for bipolar maintenance therapy in patients without a seizure disorder. Lamotrigine is used to treat bipolar depression in non-epilepsy patients. Therefore, these AEDs are first-line treatment for comorbid epilepsy and bipolar depression.12
Using antidepressants
Effectively treating depression in epilepsy patients (Algorithm) encompasses assessment of prescribed AEDs and the use of antidepressants, electroconvulsive therapy (ECT), and psychotherapy. No evidence indicates that any 1 antidepressant is more effective than others for treating depression in patients with epilepsy. When starting an antidepressant, consider the drug’s effect on seizure threshold, its efficacy, and drug-drug interactions.
