Multicentre randomised double-blind, placebo-controlled 2x2 factorial trial investigating the effects of adding mirtazapine and folic acid to existing therapy for patients with schizophrenia

The combination of mirtazapine plus antipsychotic potentially offers considerable benefit for patients with schizophrenia. Folic acid is a promising adjunctive therapy for schizophrenia that may also provide benefits for patients with other mental disorders. Furthermore the effects of folic acid may be affected by genotype.

The trial will investigate the effects of adding mirtazapine and the effects of adding folic acid to treatments for schizophrenia. At randomisation, patients will be separately randomised to mirtazapine or placebo and to folic acid or placebo.

Randomised, double-blind, placebo-controlled 2x2 factorial trial with 12-week follow-up.

Inclusion Criteria:

1. Inpatients or outpatients age 18 to 70 years;
2. Meet DSM-IV criteria for schizophrenia;
3. Signed an informed consent form by patients or their legally acceptable representatives;
4. PANSS total score >=60 and at least one item of P1, P2, P3, P5 or P6 >=4 to ensure subject has current active psychotic symptoms - i.e. hallucinations, delusions, thought disorder;
5. Subjects who are currently taking effective dose of antipsychotic;
6. Women must agree to practice an effective method of birth control if they are sexually active before entry and throughout the study.

Exclusion Criteria:

1. Meet any other DSM-IV Axis I disorders;
2. Meet DSM-IV criteria for substance abuse or dependence;
3. Have been treatment-resistant to 2 or more kinds of antipsychotics with sufficient dosage for at least 4 weeks, or require clozapine treatment, or have received clozapine treatment within 1 month prior to randomization;
4. Subjects are actively suicidal or judged clinically to be at risk of serious suicidal or violent behavior in the opinion of the investigator;
5. Have serious or unstable medical illness (e.g., cardiovascular disease, neurologic, hematologic, renal, hepatic, immunologic, endocrine, or other systemic illness), or have any clinically significant abnormality on laboratory test or ECG which indicate severe medical conditions;
6. Have received electroconvulsive therapy within 28 days before randomization;
7. Have received long acting antipsychotic within 1 treatment cycle before randomization;
8. Have received antidepressant within 14 days, or have received MAOIs within 4 weeks before randomization or require antidepressive treatment;
9. History of prostatic hypertrophy or dysuria;
10. History of narrow-angle glaucoma or elevation of intraocular pressure;
11. Known or suspected history of allergy or have contradiction to mirtazapine or folic acid;
12. Known have currently requirement of taking mirtazapine or folic acid;
13. Women who are pregnant or nursing;
14. Have previously completed or withdrawn from this study, or participated in a clinical trial of another drug within 30 days.