Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial.
The Journal of clinical psychiatry 2005 Aug 1; 66(8):1012-5
Tiihonen J J, Halonen P P, Wahlbeck K K, Repo-Tiihonen E E, Hyvärinen S S, Eronen M M, Putkonen H H, Takala P P, Mehtonen O OP, Puck M M, Oksanen J J, Koskelainen P P, Joffe G G, Aer J J, Hallikainen T T, Ryynänen O OP, Tupala E E
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland. jari.tiihonen@niuva.fi
OBJECTIVE: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication. METHOD: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003. RESULTS: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms. CONCLUSION: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.