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Lamotrigine Improves Symptoms in Patients With Treatment-Resistant Schizophrenia

The glutamate antagonist lamotrigine may benefit patients with treatment-resistant schizophrenia, according to the findings of a new randomised trial.

"Our results show the first evidence from a randomised controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia," the authors point out, "and indicate that both positive and general psychopathological symptoms in these schizophrenic patients can be controlled by a drug that is not a dopamine antagonist."

According to Jari Tiihonen, MD, with the Helsinki University Central Hospital, University of Helsinki, Finland, and colleagues, since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists.

However, recent research indicates that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by the glutamate antagonist lamotrigine.

In their analysis, Dr. Tiihonen and colleagues evaluated whether lamotrigine was more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine.

In a 14-week, crossover trial, 34 hospitalised treatment-resistant patients with chronic schizophrenia were given 200 mg/day lamotrigine that was gradually added to their ongoing clozapine treatment. The Positive and Negative Syndrome Scale were used to assess the patients at the beginning and end of each treatment period.

In the intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (P = .009) and general psychopathological (P = .030) symptoms although no improvement was observed in negative symptoms.

According to the researchers, the results suggest that the anticonvulsant agent lamotrigine can be used in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist.

"It remains to be seen if lamotrigine augmentation can hasten or enhance the recovery in acute schizophrenic psychosis and if lamotrigine has any beneficial effect on schizophrenic symptoms when used alone without concomitant medication," they conclude.



Biol Psychiatry 2003;54:1241-1248. "Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial"

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