Dextromethorphan acts as N-methyl-D-aspartate (NMDA) antagonist. In Treatment resistant schizophrenia(TRS) the efficacy of treatment response by clozapine is only around 40%. Numerous augmentation agent have been tried which includes antipsychotics, anticonvulsants, antidepressants and NMDA antagonist. The NMDA antagonist such as Riluzole and Memantine have shown good efficacy in TRS. Therefore we are evaluating NMDA antagonist, dextromethorphan in TRS. The dextromethorphan or placebo will be administered along with clozapine in TRS patients. The study is randomized double blind placebo controlled group sequential trial.

Inclusion Criteria:

• Schizophrenia patients who are diagnosed as treatment-resistant schizophrenia (TRS) defined as having been tried and not responded to any two antipsychotic medication for a duration of 6 weeks with dose equivalent of 600 mg of chlorpromazine and initiated on clozapine for the treatment of the same.
• The patients who are on stable dose of clozapine.
• Patients of either sex with age >18 years.
• Patients for whom legally authorized representative (LAR) are willing to give informed consent.

Exclusion Criteria:

• Patients with significant medical comorbidity.
• Patients with significant psychiatric comorbidity.
• Patients having active substance abuse history during the time of screening.
• Female patients who are pregnant or in reproductive age not using contraception.
• Female patients who are breast feeding

Necessary data can be requested from the principal investigator.