Topiramate improves deficit symptoms in a patient with schizophrenia when added to a stable regimen of antipsychotic medication

Topiramate was shown to attenuate the severity of negative symptoms (e.g., emotional withdrawal) in a patient with schizophrenia when added to his stable regimen of antipsychotic medication. Topiramate was administered for a period of 12 weeks: during the first 4 weeks, dosage was adjusted to the maximal tolerated dose (i.e., 175 mg/d), and, thereafter, this dosage was maintained for 8 weeks. Topiramate was studied because of recent data and hypotheses suggesting that N-methyl-D-aspartate receptor hypofunction, dampened GABAergic inhibition, and excessive stimulation of the kainic acid (KA)/alpha -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) class of glutamate receptors occur in at least some patients with schizophrenia, especially those with persistent negative symptoms and progressive psychosocial deterioration. Topiramate is a recently approved and marketed medication for the treatment of seizure disorders, whose mechanism of action includes potentiation of GABAergic neurotransmission and antagonism of KA/AMPA glutamate receptors. This case is presented because of the dramatic response of negative symptoms to the addition of topiramate. The severity of negative symptoms was assessed formally with the Negative Scale of the Positive and Negative Syndrome Scale. The negative symptoms of schizophrenia are usually resistant to most behavioral and pharmacologic interventions.