Efficacy and tolerability of antibiotic augmentation in schizophrenia spectrum disorders – A systematic literature review

Abstract

Background: A large number of augmentation agents have been tried in patients with schizophrenia spectrum disorders, because negative and cognitive symptoms are difficult-to-treat with current pharmacological agents, and because the high percentage of treatment-resistant cases requires new therapeutic solutions. Inflammation is one of the supposed pathophysiological mechanisms in schizophrenia; therefore, antibiotics have been explored as add-on agents. No systematic review or meta-analysis about the efficacy of antibiotics in psychotic disorders has yet been conducted. Objectives: To assess if the use of antibiotics as add-on to current antipsychotic treatment may improve core symptoms of schizophrenia spectrum disorders, global clinical status, overall functionality, and if this augmentation strategy is well tolerated. Methods: A systematic literature review was conducted, including papers published between 1980 and 2018, which have been found in the main electronic databases (PubMed/MEDLINE, CINAHL, NCBI, Embase, Thomson Reuters/Web of Science). The keyword search strategy was formulated using the following paradigm: „schizophrenia spectrum disorders”/ „schizophrenia”/ „schizo-affective disorder”/ „schizophreniform disorder”, AND „antibiotics”/ all the names of currently marketed antibiotics classes. This review was registered to PROSPERO database with the protocol number CRD42019119152. Results: Based on reviewing the selected trials regarding the efficacy of antibiotics over core symptoms of schizophrenia, only two agents were detected – minocycline and D-cycloserine. Minocycline as add-on to antipsychotic treatment was associated with mixed results, while regarding the efficacy of d-cycloserine either no significant difference, or superiority to placebo over negative and cognitive symptoms was reported. Minocycline had an overall effect over the clinical impression that was not distinguishable from placebo, although there was one trial supporting the efficacy of this antibiotic. The impact of minocycline over the global functioning when added to antipsychotic in patients with schizophrenia was mixed, with one positive and one negative trial (moderate to high quality designed trials). D-cycloserine had no significant impact over global clinical status or patients’ overall functionality. Conclusion: From all the data reviewed and hierarchized resulted that larger trials are needed in order to confirm the efficacy of antibiotics as add-on to antipsychotics over negative and cognitive symptoms of schizophrenia spectrum disorders.