Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial

Abstract

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37-108.37), 85.68 (74.67-96.70) and 76.87 (66.06-87.69), respectively; compared with 101.87 (90.37-113.37), 100.31 (89.29-111.32) and 100.56 (89.74-111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.

Treatment of clozapine-associated weight gain: a systematic review

“…However, this is based on a limited number of randomized controlled trials [30,43,51,55,56]. Orlistat appears to be effective in decreasing body weight in men but not women [58,59].…”

“…Of the four pharmacological treatments that have shown beneficial results, metformin and topiramate have marginally better empirical evidence for being used clinically. Topiramate may also be limited by its side effect profile: For example, paresthesia was reported in topiramate-treated subjects in both studies [43,44], as well as psychomotor disturbances and drooling in the Afshar et al [43] study. While metformin shows some benefit, a number of new antidiabetic drugs have been approved in recent years, and study with these is warranted.…”

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

“…The 3 RCTs 55,57,58 on topiramate as clozapine augmentation strategy, including 89 patients, showed a trend toward superior effect over placebo in reducing total symptom severity, but the data were heterogeneous. The study by Afshar et al 57 was considered an outlier. After removal, the trend disappeared.…”

“…The study by Afshar et al 57 was considered an outlier. After exclusion, the significant effect disappeared and heterogeneity decreased.…”

Metabolic and Cardiovascular Adverse Effects Associated with Treatment with Antipsychotic Drugs

“…44,45 If behavioral interventions fail, additional drug treatment might be indicated. Drug therapies that have been found to have efficacy in lessening weight gain and metabolic changes from antipsychotic medication include metformin, 46e48 topiramate, 49,50 and amantadine. 51,52…”