Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial.
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.


METHODS
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.


CONCLUSIONS
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.
Tiihonen
Jari
J
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital, Kuopio, Finland. jari.tiihonen@niuva.fi
Halonen
Pirjo
P
Wahlbeck
Kristian
K
Repo-Tiihonen
Eila
E
Hyvärinen
Soile
S
Eronen
Markku
M
Putkonen
Hanna
H
Takala
Pirjo
P
Mehtonen
Olli-Pekka
OP
Puck
Martin
M
Oksanen
Jorma
J
Koskelainen
Pasi
P
Joffe
Grigori
G
Aer
Juhani
J
Hallikainen
Tero
T
Ryynänen
Olli-Pekka
OP
Tupala
Erkki
E
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D010919:Placebos; D000077236:Topiramate; D005632:Fructose