Antiepileptic drugs in schizophrenia: a review

Abstract

The first choice group of psychotropic agents in schizophrenia is neuroleptics. However, this treatment is not effective in all patients and with every symptom. We summarize papers published on the role of antiepileptic drugs in treatment-resistant schizophrenia. We have searched the computer database system MEDLINE for relevant articles including reviews, reports of drug studies and case histories. Antiepileptic drugs can change symptoms of schizophrenia by their action on GABA-ergic neurotransmission or via anti-glutamatergic mechanisms. High doses of adjunctive benzodiazepines reduce positive symptoms, anxiety, and agitation. Carbamazepine is effective in affective symptoms of schizophrenia and influences violent behavior in psychotic patients. Its anti-kindling action may represent a promising treatment strategy for some patients with chronic course of schizophrenia. Valproate treatment leads to a decrease in positive symptoms as well as hostility. Lamotrigine is expected to influence the positive, negative, affective, and cognitive symptoms of schizophrenia. New antiepileptics (e.g., gabapentin, oxcarbazepine, topiramate, vigabatrin) present a promise as potential adjuncts to neuroleptic treatment in resistant symptoms of schizophrenia.

Glutamatergic antipsychotic drugs: a new dawn in the treatment of schizophrenia?

“…Lamotrigine has been shown to reverse positive, negative and cognitive symptoms associated with ketamine administration in healthy volunteers [Hosak and Libiger, 2002], and to reverse ketamineassociated changes in brain function measured using fMRI [Deakin et al 2008]. A recent meta-analysis suggests that lamotrigine, in contrast to drugs acting through glycine enhancement of NMDA receptor function, is effective as Figure 5.…”

N-Methyl-d-aspartate receptors as a target for improved antipsychotic agents: novel insights and clinical perspectives

“…This leads to an increase in downstream glutamate release onto AMPA and other classes of glutamatergic receptor mediating pro-psychotic effects. One implication of this hypothesis is that drugs reducing glutamate release, such as lamotrigine (Anand et al 2000;Hosak and Libiger 2002;Tiihonen et al 2003) or presynaptic metabotropic receptor agonists (Moghaddam 2002;Schoepp and Marek 2002;Winter et al 2003), may be useful antipsychotic agents-though they might exacerbate hypoactivity at certain populations of NMDA sites. Alternatively, antagonists at AMPA receptors may be of interest as antipsychotic agents (Mathé et al 1998;Johnson et al 1999;Sebban et al 2002;Takahata and Moghaddam 2003), though this notion is diametrically opposed to the abovementioned use of AMPAkines as cognitive enhancers.…”

Valproic acid decreases cell proliferation and migration in the cerebellum of zebrafish larvae

“…This compound is one of the major drugs administered to suppress seizures in humans and a variety of animal models (Gobbi & Janiri 2006;Jessberger et al 2007). VPA is also used to treat bipolar disorders, social phobia, neuropathic pain (Winterer & Hermann 2000;Hosák & Libiger 2002;Smith et al 2010), and neurodegenerative disorders such as Huntington's disease and Alzheimer's disease (Ren et al 2004;Qing et al 2008;Zádori et al 2009). However, VPA exposure during the prenatal and postnatal periods is also known to have severe negative effects on the brain and behavior at later adult stages.…”