DAAOI-1 Treatment for Treatment-resistant Schizophrenia

Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue at present. According to the N-methyl-D-aspartate (NMDA) hypothesis, adjuvant NMDA-enhancing agents may have therapeutic benefit. DAAOI-1, a D-amino acid oxidase (DAAO) inhibitor, is a NMDA-enhancing agents. The aim of this project is to examine the effectiveness and safety of DAAOI-1 adjuvant treatment for clozapine-resistant refractory schizophrenia patients in a randomized, double-blind, placebo - controlled trial.

Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue at present. Among schizophrenia patients, around 20-25%are treatment-resistant. According to the N-methyl-D-aspartate (NMDA) hypothesis, many clinical trials on NMDA-enhancing agents were studied. Adjuvant NMDA-enhancing agents, including glycine, D-amino acids (D-serine, D-alanine), and sarcosine (a glycine transporter I inhibitor), revealed beneficial but limited efficacy for positive and negative symptoms. The investigators recently started to study the potential of DAAOI-1, a D-amino acid oxidase (DAAO) inhibitor which can elevate synaptic concentration of D-amino acids. The aims of this project is to examine the effectiveness and safety of DAAOI-1 adjuvant treatment for clozapine-resistant refractory schizophrenia patients in a randomized, double-blind, placebo - controlled trial.

The severity of psychiatric symptoms will be assessed by: Positive and Negative Syndrome Scale(PANSS) Assessment of Negative symptoms(SANS) Global assessment of function(GAF) Quality of life scale(QOL)

Inclusion Criteria: Fulfilled the DSM-IV criteria of schizophrenia Poor responder of clozapine: a 12-week treatment without satisfactory response: a minimal total score of 70 on the Positive and Negative Syndrome Scale (PANSS) (Kay 1987), and a minimal total score of 40 on the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen 1983). Agree to participate in the study and provide informed consent Exclusion Criteria: Meet DSM-IV criteria of other AXIS I disorder, current substance dependence or mental retardation Serious medical or neurological illness Pregnancy or lactation Use of depot antipsychotic in the past 6 months Inability to follow protocol.