Current medications have only a limited effect on two core symptoms of schizophrenia, negative symptoms and cognitive deficits. Minocycline is a second-generation tetracycline which has a beneficial effect in various neurological disorders. In the past years, various findings from clinical studies showed its potential role for the treatment of these symptoms of schizophrenia. The current study aims to examine the efficacy of minocycline as add-on treatment for alleviating positive, negative and cognitive symptoms in schizophrenia patients.The current study is a single center, double-blind, randomized study that assess the adjuvant therapeutic effect of minocycline vs. placebo added to antipsychotic medications, in adult patients suffering from schizophrenia. Patients will be recruited and randomly allocated to a minocycline or placebo treatment (200 mg/day) for 6 weeks of treatment. In addition, all patients will receive probiotics (450mg/day) in order to prevent any gastrointestinal influences of antibiotics administration. Positive and negative symptoms , as well as cognitive functions will be assessed before and after treatment.

Inclusion Criteria:

1. Men and women 18-60 years of age.
2. Diagnostic and Statistical Manual (DSM) 5 diagnosis of Schizophrenia/ Schizo effective disorder based on the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID) for schizophrenia and confirmed by two senior psychiatrists.
3. Initiated on treatment with stable dosage (within +/- 25%) of atypical anti-psychotic medication for at least 6 weeks.
4. Capable and willing to provide informed consent.
5. Able to adhere to the treatment schedule.
6. Able to read, hear, write and speak the local language.
7. Has signed a written informed consent to participate in the study.

Exclusion Criteria:

1. Patients with acute, unstable, or decompensated medical condition.
2. Present substance abuse.
3. Major depression (MDD) diagnosis.
4. Attention deficit/ hyperactivity disorder (ADHD/ADD) diagnosis.
5. Cognitive dysfunction, such as Alzheimer disease or retardation.
6. Acute psychotic state.
7. Aggressive or violent patient or with vast history of aggressive or violent behavior.
8. Diagnosis of Borderline/ Anti Social/ Narcissistic personality disorders.
9. Previous sensitivity to Minocycline.
10. Current suicidal ideation or history of a suicide attempt in the past three years
11. Known or suspected pregnancy or women of childbearing potential not using a medically accepted form of contraception .(if using oral contraceptives, during the Minocycline treatment, subject should use an additional contraceptives), or women who are breastfeeding.
12. Subjects who are taking a known contraindication to Minocycline treatment (anti-coagulants, other antibiotics (of the penicillin group), methoxyflurane, Isotretinoin).
13. Subjects who had received treatment with Minocycline or β-lactam antibiotics in the preceding half year before study entry.
14. Subjects who are under compulsory hospitalization.
15. Subjects with medical history of Intestinal disease, Peptic ulcer or gastritis.