Schizophrenia Bulletin Advance Access first published online on February 4, 2009
This version published online on June 16, 2009
Schizophrenia Bulletin, doi:10.1093/schbul/sbn191
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Trimethoprim as Adjuvant Treatment in Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial
2 Department of Psychiatry, Faculty of Medicine
3 Aklilu Lemma Institute of Pathobiology
4 Department of Community Health, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
5 Health Service and Population Research Department
6 Section of Neurobiology of Mood Disorders, Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, UK
1 To whom correspondence should be addressed; tel: 00251 911 403088, fax: 00251 115 511079, e-mail: shibreteshome{at}yahoo.com.
Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable.
Keywords: schizophrenia / infectious etiology / Toxoplasma gondii / randomized controlled trial / Ethiopia
Updated to include all authors.