Metronidazole-induced Mania: Recurrence with Re-challenge

Abstract

Purpose: Antimicrobial-induced mania, termed “antibiomania”, is exceptional and only reported in isolated case reports. Assigning causation of a rare adverse event to a particular therapy or condition is challenging. Definite cause-and-effect relationships are commonly absent. We report a case of metrondiazole-induced mania, reappearing with drug re-administration to alert physicians to a very rare adverse effect of a common medication. Case: A 57 year old man developed watery, non-bloody diarrhea a few days after taking levofloxacin for upper respiratory complaints. He was 3 years post-stem cell transplant for acute myelogenous leukemia and was being treated for graft versus host disease. Medications included prednisone 15 mg/day, tacrilomus, insulin, and long-term sulfamethoxazole- trimethoprim, fluconazole and acyclovir prophylaxis. Metronidazole was begun for symptoms. After 2 doses, he was noted by family, including a physician-daughter, to be hyperactive, expansive, talking excessively, grandiose - claiming special intuition about people with disordered thought processes. The next morning, his mood and thought processes had returned to normal baseline function. Because diarrhea persisted, he took another dose of metronidazole, but not levofloxacin. One hour later, disordered mood and thought reappeared. He went to the Emergency Department, where mania was diagnosed. He was treated with one dose of olanzapine and was normal the next day. Levofloxacin was restarted to finish a 5 day course and vancomycin was used with success for the diarrhea. There was no recurrence of the mania or diarrhea over a 2-year follow-up. Conclusion: Antibiomania is quite rare, most commonly attributed to clarithromycin, isoniazid and fluroquinolones. Less than 10 possible instances have incriminated metronidazole. We postulate that our patient had metronidazole-induced mania, perhaps potentiated by low-dose steroids and other antimicrobials. Further assessment difficulty exists because of single case reports of mania possibly induced by both acyclovir and sulfamethoxazole. Our case is highly unusual because documented recrudescence of symptoms occurred with drug re-administration; thus, this case may satisfy WHO criteria for definite rather than probable or possible causality, rare in single cases of putative drug reactions. Symptoms were of acute onset, temporally related to metronidazole use and self-limited with drug discontinuation. Prompt recurrence with re-challenge is striking. Antibiomania is rare, but should be considered with new onset of acute mania. Contribution of other medications is unclear and the mechanism is speculative.