Minocycline Augmentation in Schizophrenia

Minocycline, which is a second-generation tetracycline, has been found to inhibit Nitric Oxide Synthase (NOS) and inflammatory cytokines. These are some of the primary mechanisms that have been proposed to explain its neuroprotective and neuroplastic effects in several animal and human models of neurological and psychiatric diseases, including Parkinson's disease and schizophrenia. There are only three clinical trials with minocycline in schizophrenia subjects. A more definitive clinical trial in a larger sample with optimized and cost-effective design using a comprehensive cognitive battery and a global assessment of schizophrenia symptom domains is necessary to examine the efficacy of minocycline. If minocycline improves psychopathology and potentially other symptoms (including cognitive function) for schizophrenia, the treatment could be easily implemented in the existing treatment delivery system at relatively low cost and have the potential for making a significant public health impact. The investigators plan to recruit 120 individuals with early course schizophrenia who are currently on second-generation antipsychotic (SGA) medications and are experiencing persistent symptoms in at least the moderate range. In an effort to limit placebo response, which is notoriously high in psychiatric population, the investigators are using an adaptive design. Since, there is growing evidence to support the inflammatory hypothesis of schizophrenia, the investigators will also explore whether cytokine levels mediate the response from minocycline treatment.