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.

Inclusion Criteria:

1. Ages between 18-35 years

2. Males & females

3. Current DSM-IV diagnosis of schizophrenia or schizoaffective disorder confirmed by
the Mini-International Neuropsychiatric Interview (M.I.N.I.) conducted by a trained
psychiatrist.

4. Treatment with a stable dose of second generation antipsychotic medication for at
least 1 months prior to study entry 200-600 mg/day chlorpromazine equivalent doses);

5. Evidence of stable symptomatology for 12 weeks as evidenced by no hospitalizations
for schizophrenia, no increase in level of psychiatric care due to worsening of
symptoms, no ER use for symptoms of schizophrenia and no significant changes to
antipsychotic medication or dose (>25%) in the past 12 weeks.

6. Baseline total score between 40 and 65 on the Brief Psychiatric Rating Scale (BPRS);

7. Raw score of 12 or higher on the Wechsler Test of Adult Reading (WTAR) (estimates
premorbid IQ).

8. Able to comprehend the procedure and aims of the study to provide informed consent

Exclusion Criteria:

1. Acute, unstable, significant or untreated medical illness beside schizophrenia;

2. Pregnant or breast-feeding females;

3. History of substance abuse or dependence in the past 3 months.

4. Known contraindication to minocycline treatment.

5. Treatment with minocycline or Beta-lactam antibiotics in the preceding half year
before study entry.