Evidence-Based Reviews

How seizure disorders change depression treatment

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Suicide risk is high in depressed patients with epilepsy, especially the temporal lobe form.



Ms. A, age 29, has had depression for 6 years and has taken antidepressants with inconsistent response. For 3 weeks, while not taking any antidepressant, she reports loss of energy; feeling sad, subdued, and tearful; poor concentration; and reduced interest in enjoyable activities including sex, the same symptoms she ?rst reported 6 years ago. She has no appetite but has not lost weight.

Several times a month Ms. A “loses” short periods of time. For example she says sometimes she cannot remember what happens between parking her car and sitting at her desk at work. After these episodes, which began 9 years ago, her speech is slightly slurred, and coworkers tease her about being “hungover.” She feels fuzzy-headed, but her speech and thinking clear after a few hours. At other times she smells burning rubber and feels that everything she does repeats what she has done before. Sometimes she feels “out of body” and can watch herself from the ceiling.

Ms. A’s symptoms suggest a seizure disorder. Her depressive features appeared after these ictal episodes began 9 years ago.

Recognizing mood disorders in patients with epilepsy is important because these disorders can be successfully treated within the context of the medical condition.

Many cases of comorbid depression in epilepsy are undiagnosed. A study of 100 patients with refractory epilepsy and depression severe enough for pharmacotherapy found that referral for psychiatric treatment was delayed >1 year in 75% of patients with spontaneous mood disorders and 89% of patients with depression secondary to antiepileptic drugs (AEDs).1

Psychiatrists often are called on to evaluate and treat depression in epilepsy patients or to assess for nonadherence to AEDs. Successfully treating these patients requires understanding:

  • the relationship between epilepsy and depression
  • the etiology of depression in patients with seizure disorder
  • how to treat depression in this population.

High comorbidity

Depression rates are higher in epilepsy patients than in the general population (1% to 3% of men, 2% to 9% of women).2 Depression can be diagnosed in:

  • 20% to 30% of patients with recurrent seizures
  • 6% to 9% of patients in remission
  • 50% to 55% of patients attending hospital epilepsy clinics and video telemetry units.3
Major depressive disorder is more common and severe in patients with a seizure disorder than in those with other neurologic and chronic medical conditions.4 Men with epilepsy have a higher risk of developing depression, whereas in the general population depression is more prevalent in women.5 Major depression may be more common in patients with complex partial seizures—specifically temporal lobe epilepsy (TLE), the most common form of epilepsy in adults.4 An estimated 3% to 21% of epileptic patients have dysthymic disorder.5 The prevalence of bipolar disorder in this population is unknown.

Temporal relationship. Depression can be preictal, ictal, postictal, or interictal.4 One-third of patients with partial seizures report premonitory symptoms, usually before secondary generalized tonic clonic seizures.5

  • Preictal depression occurs hours to days before a seizure and often is relieved by the convulsion.
  • Ictal depression—more common in TLE—occurs as an aura in approximately 1% of patients. Onset is sudden and ranges from mild sadness to profound helplessness and despair. Treating the seizures also treats the depression.
  • Postictal depression in TLE patients lasts hours to days after a seizure.
  • Interictal depression affects up to two-thirds of epilepsy patients, especially those with severe or frequent seizures. Treat interictal depression separately from the Seizures.

Differential diagnosis

Assessing and treating a depressive episode is similar in patients with or without epilepsy. In medically ill patients, DSM-IVTR recommends using diagnostic criteria for major depression and treating the depression whatever its cause.

Search for seizure cause. Although 70% of epilepsies are idiopathic, search for the cause of a patient’s seizures. Neuroimaging can rule out a stroke, cerebral tumor, or traumatic brain injury as the cause of both depression and epilepsy.4 Even after exhaustive study, 10% to 20% of epilepsy cases cannot be identified by electroencephalography (EEG).

Seizure type and location, severity, laterality of seizure focus, and frequency are important variables in the etiology of depression in patients with epilepsy.6 Similar changes in neurotransmitters—serotonin, noradrenaline, dopamine, and gamma-aminobutyric acid—are observed in both depression and epilepsy.5

Characterize depressive symptoms. Consider involving the patient’s spouse or partner in the discussion to validate and augment the patient’s report. Often patients describe depressive symptoms— such as sleep problems, changes in appetite, loss of libido, and impaired cognition—that could be side effects of AEDs or symptoms of epilepsy.


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