Topiramate augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study

Abstract

The persistence of psychotic, affective, cognitive, and psychosocial symptoms despite medications is commonly observed in schizophrenic patients. The present study was a 24-week double-blind, randomized, placebo-controlled trial aimed to explore the efficacy of topiramate add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of treatment-resistant schizophrenic patients receiving clozapine. After clinical and cognitive assessments were randomly allocated to receive either up to 200 mg/day of topiramate or a placebo. A final sample of 43 patients completed the study. The results obtained indicate that topiramate appeared to be scarcely effective for reducing clinical symptomatology in schizophrenic patients who have had an incomplete clinical response to clozapine. Regarding cognitive functioning, in our sample a trend to experience cognitive impairment in the examined domains was observed, as the patients included in the topiramate groups expressed cognitive complaints partially confirmed by a mild worsening of performances on certain cognitive tasks. Schizophrenia is a heterogeneous disorder with regard to pathophysiology; therefore, data reflecting the mean response of a sample of patients may fail to reveal therapeutic effects. More research is needed to better identify subgroups of patients with peculiar features which may account for responsivity to experimental medications and augmentation strategies.

Polypharmacy for schizophrenia

“…Similar benefit was also seen with duloxetine in a study by this same group[9], but not with topiramate. [10] There remains no clear recommendation for how to augment clozapine or what other strategies to employ when an individual does not tolerate or respond meaningfully to clozapine.…”

May Non-antipsychotic Drugs Improve Cognition of Schizophrenia Patients?

“…Of note, 19 patients received topiramate and 24 placebo: the Winsconsin Card Test scores of the topiramate group did not significantly change compared to placebo [43]. These results have not been confirmed by further studies.…”

“…In a 24-week double-blind, randomized, placebo-controlled trial adjunctive topiramate (up to 200 mg/day) to clozapine even worsened cognitive functioning of 43 treatment-resistant schizophrenia patients [43]. Of note, 19 patients received topiramate and 24 placebo: the Winsconsin Card Test scores of the topiramate group did not significantly change compared to placebo [43].…”

Glutamatergic agents for schizophrenia: current evidence and perspectives

“…Several studies suggested topiramate's efficacy for treatment-resistant positive and negative symptoms [96,97], in particular in patients with partial response to CLZ. However, significant superiority over placebo could not be demonstrated in a recent meta-analysis [87], and worsening of cognitive abilities might be a potential side effect [98,99]. Some investigators also intended to reduce appetite and body weight in schizophrenia [96][97][98][99] or bipolar disorder [100].…”

“…However, significant superiority over placebo could not be demonstrated in a recent meta-analysis [87], and worsening of cognitive abilities might be a potential side effect [98,99]. Some investigators also intended to reduce appetite and body weight in schizophrenia [96][97][98][99] or bipolar disorder [100]. In line with a recent review on the benefits and the risks of topiramate treatment in schizophrenia [101], further research in patients in early disease stages seems necessary.…”