The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: A double-blind, placebo-controlled study

Abstract

Based on the evidence that lamotrigine added to clozapine in refractory schizophrenic patients has reported promising results, the present 24-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and neurocognitive assessments patients were randomly allocated to receive, in a double-blind design, either up to 200 mg/day of lamotrigine or a placebo. A final sample of fifty-one patients completed the study.The results obtained indicate that lamotrigine added to stable clozapine treatment showed a beneficial effect on the negative, positive and general psychopathological symptomatology in a sample of treatment-resistant schizophrenic patients. Regarding cognitive functions, improvement was observed in some explored areas, such as attentional resistance to interference, verbal fluency and executive functioning. The findings provide evidence that lamotrigine augmentation of clozapine treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant schizophrenia.

Pharmacological Augmentation Strategies for Schizophrenia Patients With Insufficient Response to Clozapine: A Quantitative Literature Review

“…Tiihonen 79 quantitatively summarized the effect of lamotrigine addition, including the same studies as in this review. As they did not identify Zoccali et al 56 as an outlier, they arrived to a slightly more positive conclusion.…”

“…Again, Zoccali et al 56 was an outlier. After exclusion, Hedges's g decreased and heterogeneity disappeared.…”

“…Figure 2 plots the individual effect sizes per study regarding total symptom score from the PANSS or BPRS rating scales. The study by Zoccali et al 56 was considered an outlier and therefore excluded from analysis. After exclusion, the mean weighted effect size was no longer significant and studies were homogeneous.…”

Recent advances in treating cognitive impairment in schizophrenia

“…An initial study with lamotrigine demonstrated positive effects on cognition (Zoccali et al 2007), but these findings were not replicated in a larger study (Goff et al 2007). Selective phosphodiesterase inhibitors may possibly have beneficial effects on symptoms and on cognition in schizophrenia (Menniti et al 2007).…”

Mirtazapine add‐on therapy in the treatment of schizophrenia with atypical antipsychotics: a double‐blind, randomised, placebo‐controlled clinical trial

“…Pharmacotherapies adjunctive to antipsychotic treatment may be useful strategies to control negative symptoms. These include anticonvulsants such as lamotrigine (Zoccali et al, 2007), antioxidants such as N-acetyl cysteine (Berk et al, 2008) and antidepressants. Several studies have reported improvement in negative symptoms when antidepressants are administered as an adjunct to antipsychotics.…”