Interictal psychosis is a serious comorbid condition in epilepsy patients that would benefit from treatment with psychotropic medication.

This paper gives an overview of the pathophysiology, symptomatology and treatment of the schizophrenia-like psychosis of epilepsy. Use of the term ‘interictal chronic psychosis’ is suggested, to conform to current DSM-IV classification of schizophrenia.

Literature review supplemented by clinical experience. There is a lack of randomized control trials (RCTs) concerning effectiveness and side-effects of neuroleptics in epilepsy patients.

Hypotheses concerning the pathophysiology of the interictal chronic psychosis are discussed. The concept of forced normalization and alternative psychosis is based on case descriptions, and was not substantiated by systematic research. The kindling hypothesis seems promising, but was never confirmed in humans. A third theory, supported by some studies, suggests that inhibitory cerebral mechanisms enhance psychotic symptoms in epilepsy patients. Treatment strategies are based on case studies and open studies by lack of RCTs. Treatment should consider the optimalization of the dosage of antiepileptics in combination with one or two antidepressants, mood stabilizers and/or atypical neuroleptics. Surgery plays no significant role in the treatment of treatment-refractive epilepsy with interictal chronic psychotic symptoms.

There is a prominent role of antidepressant or double antidepressant treatment strategies in patients with epilepsy and interictal chronic psychosis compared with treatment guidelines of chronic psychotic patients in general psychiatry.