Clarithromycin-induced mania with psychotic features: the diagnostic challenge of differentiating primary psychiatric disorders from organic neuropsychiatric syndromes

Background

“Antibiomania” is a rare phenomenon characterised by acute manic symptoms following antibiotic administration [1]. A recent systematic review (2026) identifies clarithromycin as the most frequently implicated agent [2]. Proposed mechanisms include increased neuronal excitability via GABA-A receptor antagonism, blood-brain barrier penetration by lipophilic metabolites, and disruption of the gut-brain axis [2,3]. We present a case of clarithromycin-induced mania mimicking autoimmune/infectious encephalitis or a primary manic episode, highlighting clinical markers that distinguish iatrogenic mania and psychosis from primary psychiatric disorders.

Case Presentation

A woman in her 30s presented to the Emergency Department (ED) with a one-week history of fever, headache, otalgia, and odynophagia. She had self-medicated with amoxicillin/clavulanic acid for seven days without psychiatric symptoms. Her history included a single depressive episode in 2019. In 2024, following a teratoma diagnosis, she resumed fluoxetine (20 mg/day) as a prophylactic measure, remaining clinically stable and high-functioning. Family history was notable for schizophrenia, but the patient had no prior manic or psychotic episodes. On Day 10, she was prescribed oral clarithromycin (500 mg twice daily) and topical corticosteroids for acute sinusitis. Within 48 hours, she developed a florid clinical picture: racing thoughts, auditory pseudo-hallucinations (catastrophic content, internal localization) with partial insight, psychomotor agitation with increased energy, and disorganized behaviour. Persecutory delusions and decreased need for sleep followed by total insomnia (48 hours) were also present. Notably, she exhibited fluctuating levels of consciousness and periods of amnesia regarding the exacerbation. On Day 15, she returned to the ED due to these symptoms. Investigations were initiated to rule out secondary etiologies. Brain CT scan was unremarkable. Lumbar puncture revealed clear CSF with normal glucose, protein levels, and normal cell count, excluding infectious or autoimmune encephalitis. By the psychiatric assessment (Day 16), clarithromycin had been discontinued for 24 hours and a dose of diazepam 10mg administered. The patient had returned to her baseline, corroborated by collateral history. Mental state examination revealed euthymia and preserved cognitive function, though circumscribed amnesia for the episode’s peak persisted. She demonstrated full insight. She required no long-term antipsychotic or mood-stabilizing therapy. At three-month follow-up, she remained asymptomatic.

Conclusions

Although the presentation mimicked encephalitis and primary mania with psychotic features, the clear temporal association with clarithromycin and rapid remission support a diagnosis of “antibiomania”. Given the history of depression, a Bipolar I Disorder diagnosis could have been easily misdiagnosed; however, the presentation did not meet full DSM-5 manic criteria [4]. Per guidelines, medication-induced symptoms such as agitation and nervousness are fundamentally distinct from a primary bipolar syndrome and often insufficient for a diagnosis, lacking the necessary symptom clusters and specificity. Fluctuating consciousness and amnesia were critical cues to prioritise an iatrogenic etiology. This case demonstrates that “antibiomania” can be a severe, yet self-limiting and isolated iatrogenic event. Recognition is essential to avoid “diagnostic overshadowing” and prevent the lifelong burden of an incorrect bipolar label and unnecessary pharmacological treatment.

References

1. E.P. Meszaros, S.T. Ahmed, S. Caplow, E.A. Carr, Antibiomania: a case report of clarithromycin and amoxicillin-clavulanic acid induced manic episodes separately, BMC Psychiatry 21 (2021) 325. https://doi.org/10.1186/s12888-021-03397-7
2. T. Marković, A. Todorović, M. Stojković, S. Popović, D. Baskić, S. Matić, Antibiomania: A Systematic Review of Clarithromycin-Associated Manic Episodes, J. Clin. Psychopharmacol. 46 (2026) 82-92. https://doi.org/10.1097/JCP.0000000000002089
3. E.K. Bichler, C.C. Elder, P.S. García, Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling, J. Neurophysiol. 117 (2017) 93-103. https://doi.org/10.1152/jn.00134.2016
4. American Psychiatric Association, Diagnostic and statistical manual of mental disorders, fifth ed., American Psychiatric Association Publishing, Washington, 2013.