Clinical characteristics of forced normalization and alternative psychosis with special consideration of the new anticonvulsants

SUMMARY Background In the case of an alternative psychosis (AP) or forced normalization (FN), the patient alternates between periods of clinically manifest seizures and normal behavior, and other periods of seizure freedom or significant seizure reduction accompanied by psychosis or behavioral disturbances. In clinical practice and in the literature, the terms AP and FN are mostly used synonymously despite small differences. FN of the EEG is not only common to interictal mental disturbances but may also occur in the case of pre-ictal and postictal mental disturbances. Aim To update the 2007 review on “Alternative Psychoses of Epilepsy” in this journal with special consideration of the new anticonvulsants. Material and Methods We conducted a literature research from 1987 (in this year a psychosis, triggered by the first “new “anticonvulsant vigabatrin in a patient with epilepsy was reported for the first time) up to September 2019. Discussion AP/FN are rare events; only 10% of epileptic psychosis are AP/FN. AP/FN respectively occur with both generalized and focal epilepsy; in recent years, patients with focal epilepsy predominate. AP/FN generally present with behavioral disturbances of acute or subacute onset associated with thought disorder, delusions, hallucinations, significant mood change, or anxiety with depersonalization and derealization symptoms. The reports on EEG findings in patients with AP are inconsistent. In the case of FN, the EEG is by definition normal or substantially improved. The most prominent risk factor for the development of an AP/FN is the anticonvulsant medication. The following anticonvulsants have not been observed until now as triggers of an AP/FN in the literature reviewed by us: Acetazolamide and sulthiame (“old” anticonvulsants) and the “new” anticonvulsants brivaracetam, eslicarbazepine, pregabalin, retigabine, rufinamide, stiripentol. The treatment is based on 3 strategies: Reduction or complete cessation of anticonvulsants, change of anticonvulsants and administration of antipsychotic drugs. Conclusion The risk of an AP/FN is probably different for the individual dugs. At the current level of experience, gabapentin, pregabalin, oxcarbazepine or eslicarbazepine can be the first alternative if an AP/FN was triggered by another anticonvulsant in a patient with focal epilepsy. In generalized epilepsy, especially in patients with absences, valproic acid remains the first alternative.