Is there an improvement in psychotic symptoms and cognition impairments with the addition of lamotrigine to risperidone in chronic schizophrenia?

S. Akhondzadeh, K. Mackinejad, S. A Ahmadi-Abhari, M. Moin, Z. M. Alem. Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Research has consistently demonstrated that patients with schizophrenia suffer from cognition impairments as well as positive and negative symptoms. For years the focus of treatment for schizophrenia has been on psychotic symptoms, partly because this approach has been successful. Unfortunately, however, the effective treatment of psychotic symptoms in schizophrenia dose not reduce cognitive impairment, which causes disability and indirectly contributes to the cost of the illness. It has been reported that lamotrigine, a mood stabilizer that inhibits glutamate release, can augment clozapine treatment in patients with chronic refractory schizophrenia. In addition, lamotrigine, unlike most antipsychotic drugs, can reverse psychotomimetic symptoms induced by ketamine and it may improve some aspects of cognitive dysfunction associated with schizophrenia such as attention, learning and memory (Dursun, et al., 1999, 2001). The objective of the present study was to assess the efficacy of lamotrigine as an adjuvant agent in the treatment of patients with chronic schizophrenia and in particular its effect on cognitive performance (attention) in a 8 week double blind and placebo controlled trial.

Eligible participations in the study were 36 patients with schizophrenia. All patients were inpatients and were in the active phase of   the illness, and met DSM-IV criteria for chronic schizophrenia. Patients were allocated in a random fashion, 18 to risperidone 6 mg/day plus lamotrigine 150 mg/day and 18 to risperidone 6 mg/day plus placebo. Patients also received biperiden if they had faced extrapyramidal symptoms. Patients were assessed by a third year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks after the medication started. The mean decrease in the Positive and Negative Syndrome Scale (PANSS) score from baseline was used as the main outcome measure of response of schizophrenia to treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale. The Stroop Color Word Test was performed in a standardized fashion in a single session of about 20 minutes. Adverse events were systematically recorded throughout the study and were assessed using a checklist. The trial was performed in accordance with the Declaration of Helsinki and subsequent revisions and approved by ethics committee at Tehran University of Medical Sciences. Written informed consents were obtained before entering into the study. A two-way repeated measures analysis of variance (time- treatment interaction) was used. The two groups as a between-subjects factor (group) and the five measurements during treatment as the within-subjects factor (time) were considered. This was done for positive, negative, general psychopathology subscale and PANSS total scores. In addition, a one-way repeated measures analysis of variance with a two-tailed post-hoc Tukey mean comparison test were performed in the change from baseline in each group. To compare the two groups at baseline and the outcome of two groups at the end of the trial, an unpaired Student's t-test with a two-tailed P value was used.

Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of risperidone and lamotrigine showed a significant superiority over risperidone alone in the treatment of negative symptoms, general psychopathology symptoms as well as PANSS total scores ( F = 6.71, d.f. = 1, P=0.01). In addition, patients’ attention improved significantly in the lamotrigine group on the Stroop color naming subtest (time and error) (P=0.02 and P=0.001 respectively) . There were no significant differences between the two groups in terms of extrapyramidal symptoms and observed side effects.

The present study indicates that lamotrigine is as a potential adjunctive treatment strategy for chronic schizophrenia and it may improve the attention domain of cognition impairment associated with schizophrenia.

Dursan, et al. (1999). Archives of General Psychiatry. 56, 950.
Dursun, et al. (2001). Journal of Psychopharmacology. 15, 297-301.