Interictal depression , occurs in 25% to 55% of people with epilepsy (1,2). Further, the suicide rate of persons with epilepsy is more than five times that of controls (1,3). Interictal depression has biological mechanisms (family history of depression, structural lesions, AEDs) and psychosocial-reactive mechanisms (1,2,4–6).

  • The burden of suffering depression causes is enormous. In one study of patients with medically refractory epilepsy, depression was by far the most significant predictor of poor quality of life, overriding seizure frequency and severity (7). Depression was common (54%), underdiagnosed, and largely untreated in this population (only 17% were taking antidepressants) (7).
  • In two separate studies, use of tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs) by patients with epilepsy more frequently led to reduced seizure frequency than to exacerbation (8,9). If corroborated by larger, prospective studies, this finding may be secondary to improved sleep and mood, factors associated with reduction of seizure frequency.

Treating Depression

SSRIs and related drugs (e.g., venlafaxine and nefazodone) are the first line of therapy for most patients with depression. However, the efficacy and safety of any specific SSRI has not been proved (8). Drug interactions are more likely with fluoxetine, fluvoxamine, and paroxetine than with escitalopram, citalopram, or sertraline. Fluoxetine’s long half-life (>24 hours) is an advantage during tapering off, since it reduces the frequency of withdrawal symptoms. However, a long half-life is a disadvantage if the patient cannot tolerate the drug or experiences an adverse drug interaction.


  1. Mendez MF, Cummings JL, Benson DF. Depression in epilepsy: significance and phenomenology. Arch Neurol 1986;43:766–70.
  2. Lambert MV, Robertson MM. Depression in epilepsy: etiology, phenomenology, and treatment. Epilepsia 1999;40(suppl 10):S21–47.
  3. Matthews WS, Barbaras G. Suicide and epilepsy: a review of the literature. Psychosomatics 1981;22:515–24.
  4. Hermann BP, Whitman S. Psychosocial predictors of interictal depression. J Epilepsy 1989;2:231–7.
  5. Bromfield EB, Altshuler L, Leiderman DB, Balish M, Ketter TA, Devinsky O. Cerebral metabolism and depression in patients with complex partial seizures. Arch Neurol 1992:49:617–23.
  6. Kanner AM, Nieto JC. Depressive disorders in epilepsy. Neurology 1999;53(suppl 2):S26–32.
  7. Boylan L, Flint LA, Labovitz DL, Jackson SC, Starner K, Devinsky O. Depression but not seizure frequency predicts quality of life in treatment resistant epilepsy. Neurology (in press).
  8. Ojemann LM, Baugh-Bookman C, Dudley DL. Effect of psychotropic medications on seizure control in patients with epilepsy. Neurology 1987;37:1525–7.
  9. Gross A, Devinsky O, Westbrook LE, Wharton AH, Alper K. Psychotropic medication use in patients with epilepsy: effect on seizure frequency. J Neuropsychiatry Clin Neurosci 2000;12:458–64.

Reproduced and adapted with permission from Orrin Devinsky, M.D. and Epilepsia.

Authored By: 
Orrin Devinsky, MD
Steven C. Schachter, MD
Joseph I. Sirven MD
Reviewed By: 
Joseph I. Sirven MD
Patty Obsorne Shafer RN, MN
Thursday, August 22, 2013