Low-dose lamotrigine augmentation therapy improves residual symptoms in treatment-resistant schizophrenia: A report of five cases

Abstract

Treatment-resistant schizophrenia (TRS) refers to the approximately 20-30% of schizophrenia patients whose symptoms are resistant to any antipsychotic treatment. For the improvement of residual symptoms in TRS, augmentation therapy using anticonvulsants such as lamotrigine (LTG) has recently attracted attention. Randomized clinical trials (RCTs) have demonstrated robust evidence; however, the results have shown both positive and negative outcomes for the use of LTG. Although RCTs have merit, they also obscure informative clinical features present in each patient, such as the types of TRS that show the most significant effects from LTG. Thus, detailed case reports examining the efficacy of LTG may help to shed light on various treatments for complex, heterogeneous diseases such as schizophrenia. We present detailed reports on the clinical course and features of TRS in five patients suffering from severe positive symptoms who were treated with LTG augmentation therapy. After the administration of LTG augmentation therapy, two patients did not show any improvement in their residual symptoms, while the remaining three patients did experience improvement. Remarkably, patients with more severe residual positive symptoms, especially those with auditory hallucinations, seemed to respond better to low-dose LTG (50 mg daily). Additional clinical variables, such as type and dose of ongoing antipsychotics, age of onset, duration of illness, duration of untreated psychosis, number of administration cycles, and genetic heritability, were not found to be related to the effectiveness of LTG augmentation. Low-dose LTG augmentation therapy seems to improve residual symptoms in some cases of TRS. The glutamatergic properties of LTG may be the decisive factor in these symptoms, as other glutamatergic agents have also been shown to be effective based on previous glutamate hypotheses in schizophrenia.