Antidepressant and double antidepressant treatment for the affective disorder of epilepsy

J Clin Psychiatry. 1997 Jan;58(1):3-11. doi: 10.4088/jcp.v58n0101.


Background: About half of all patients with chronic epilepsy experience an intermittent and polysymptomatic affective disorder; fewer than 10% suffer from interictal psychotic episodes. The affective disorder responds well to treatment with tricyclic antidepressant medication. The interictal psychosis tends to develop among those with severe affective disorder, responds poorly to antipsychotic medication, and has been more difficult to treat.

Method: At the Epi-Care Center, Memphis, Tennessee, we have recently begun to treat refractory cases, both nonresponders with affective disorder and those with interictal psychosis, with the combination of a tricyclic antidepressant (TCA) and a serotonin selective reuptake inhibitor (SSRI). The double antidepressant treatment of all previously intractable patients with interictal affective disorder seen over a 20-month period at the Epi-Care Center is reported here.

Results: The outcome of the novel treatment for the most severe psychiatric disorders of epilepsy has been highly satisfactory: 15 (68%) of 22 previously unresponsive patients with affective disorder were excellent or good responders.

Conclusion: Antidepressants are the psychotropic drugs of choice for the affective disorder of epilepsy and can be effective in combined form (TCA and SSRI) for otherwise intractable patients. The paradoxical therapeutic effects of proconvulsant drugs in epilepsy conform with the hypothesis that the psychiatric complications of chronic epilepsy result from the development of seizure-suppressing mechanisms that can be mitigated by antidepressants.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Affective Disorders, Psychotic / drug therapy
  • Affective Disorders, Psychotic / etiology
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Chronic Disease
  • Drug Therapy, Combination
  • Epilepsy / complications*
  • Epilepsy / psychology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mood Disorders / drug therapy*
  • Mood Disorders / etiology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Treatment Outcome


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors