Abstract
Background
There is no evidence from randomized, controlled trials that demonstrate effectiveness
for any pharmacological treatment in clozapine-resistant schizophrenia. Since the
introduction of chlorpromazine, all antipsychotics with proven efficacy on positive
symptoms have been dopamine antagonists, but recent experimental data suggest that
ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled
by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine
is more effective than placebo in the treatment of positive schizophrenic symptoms
when combined with clozapine.
Methods
Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia
participated in a double-blind, placebo-controlled, 14-week, crossover trial where
200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical
assessments were made by the Positive and Negative Syndrome Scale at the beginning
and end of each treatment period.
Results
In intention-to-treat analysis, lamotrigine treatment was more effective in reducing
positive (effect size .7, p = .009) and general psychopathological (effect size .6, p = .030) symptoms, whereas no improvement was observed in negative symptoms.
Conclusions
These results provide the first evidence from a randomized controlled trial of an
effective pharmacological treatment with an anticonvulsant agent 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. The results are in line with previous experimental data suggesting that
excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.
Keywords
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Article info
Publication history
Accepted:
May 9,
2003
Received in revised form:
March 12,
2003
Received:
January 10,
2003
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
