Antibiomania: A Systematic Review of Clarithromycin-Associated Manic Episodes

Antibiomania, a rare adverse reaction, refers to antibiotic-induced mania, with clarithromycin most frequently implicated. Symptoms include mood elevation, hyperactivity, and hallucinations, typically resolving after discontinuation of the drug. This review examines reported cases to better characterize clinical patterns and guide clinical recognition and management.

A systematic review was conducted following PRISMA guidelines and registered with PROSPERO. Literature searches were performed in PubMed/MEDLINE, Web of Science, Scopus, and EMBASE using keywords related to clarithromycin, mania, and psychosis. Studies were included regardless of language or publication date. Data extraction focused on demographic details, clinical presentation, treatment, and causality assessment. The quality of case reports was assessed using standardized criteria. FAERS and EudraVigilance databases were queried to identify spontaneously reported psychiatric adverse events associated with clarithromycin use.

A total of 32 studies involving 34 patients were included. Most patients were under 65 years old, with a nearly equal distribution of genders. Manic episodes often included psychotic symptoms and emerged ~4 days after the initiation of clarithromycin, lasting about 3 days. The most common dosage was 500 mg taken twice daily. Rechallenge in 5 cases consistently reproduced the symptoms. Causality assessment using the Naranjo and WHO-UMC score suggested a probable association in most cases. All patients fully recovered after discontinuation.

Clarithromycin may trigger secondary mania, emphasizing the need for clinician awareness of this rare psychiatric side effect. Timely recognition and appropriate management can enhance patient outcomes and prevent unnecessary psychiatric interventions.