Antibiomania

Background

First coined in 2002 in the *Journal of Clinical Psychopharmacology*, antibiomania describes a condition where antimicrobial agents induce manic or mixed affective episodes. The initial literature review identified 21 cases, with clarithromycin being the most frequently implicated agent, followed by isoniazid, ciprofloxacin, and ofloxacin. World Health Organization (WHO) pharmacovigilance data later expanded this to 82 cases, with clarithromycin implicated in 27.6% of reports.

The exact pathophysiology remains unclear, though hypotheses include GABA receptor antagonism, altered monoaminergic neurotransmission, and interactions with the gut microbiome affecting the gut-brain axis.

Clinical Features

Patients typically present with acute onset manic symptoms within days (often 1-5 days) of initiating antibiotic therapy. Key features include:

• Mood changes: Elevated, expansive, or markedly irritable mood
• Behavioral changes: Increased goal-directed activity, restlessness, hypersexuality, or impulsivity
• Speech: Pressured speech
• Sleep: Decreased need for sleep without fatigue
• Cognition: Racing thoughts, distractibility
• Psychotic features: Grandiose or paranoid delusions (less common)

Crucially, many patients have no prior psychiatric history, though the condition can also precipitate mania in those with underlying bipolar disorder.

Differential Diagnosis

• Primary bipolar disorder (manic episode)
• Substance-induced mood disorder (cocaine, methamphetamine, steroids, antidepressants)
• Medical causes: Hyperthyroidism, Cushing syndrome, multiple sclerosis
• Serotonin syndrome (if concurrent serotonergic agents)
• Delirium (altered mental status with fluctuating consciousness)
• Acute psychosis (schizophrenia spectrum disorders)
• Other medication-induced mania (corticosteroids, levodopa, stimulants)

Evaluation

History

• Detailed medication history including recent antibiotic use (timing of initiation vs. symptom onset)
• Past psychiatric history, family history of mood disorders
• Substance use history

Physical Exam

• Complete physical exam to identify sources of infection requiring antibiotics
• Neurological exam to rule out focal deficits

Diagnostic Workup

• Laboratory: CBC, CMP, TSH, free T4, cortisol level, UA, urine toxicology screen
• Imaging: CT head if first manic episode, atypical presentation, or focal neurological findings to rule out organic causes
• ECG: If sympathomimetic toxidrome suspected or before administering antipsychotics

Key diagnostic clue is the temporal relationship between antibiotic initiation and symptom onset.

Management

Immediate Interventions

• Discontinue offending antibiotic: Consult with primary team regarding alternative antimicrobial agents for the underlying infection

Agitation Control

• Lorazepam 1-2 mg PO/IV/IM (titrated to effect)
• Droperidol or haloperidol for severe agitation with psychotic features
• Second-generation antipsychotics (e.g., olanzapine, risperidone) if bipolar mania suspected
• Supportive care: Quiet environment, limitation of stimuli, hydration

Specific Considerations

• Do not rechallenge with the same antibiotic; cross-sensitivity between macrolides has been reported
• If H. pylori treatment required, consider replacing clarithromycin with metronidazole or tetracycline (though monitor for similar psychiatric side effects)
• Psychiatric consultation for severe cases or diagnostic uncertainty

Disposition

Admission Criteria

• Severe agitation requiring chemical or physical restraints
• Suicidal or homicidal ideation
• Lacking capacity to care for self or make medical decisions
• Severe psychosis requiring inpatient psychiatric stabilization
• Medical admission if underlying infection requires IV antibiotics and psychiatric monitoring

Discharge Criteria

• Symptoms improving after antibiotic discontinuation (typically within 12-72 hours)
• Safe home environment with reliable follow-up
• Alternative antibiotic regimen established for ongoing infection treatment
• Psychiatry follow-up arranged if symptoms persist beyond expected resolution period

Most cases resolve within hours to days after discontinuation of the offending agent.

See Also

• Mania
• Bipolar disorder
• Drug-induced psychosis
• Clarithromycin
• Fluoroquinolones
• Serotonin syndrome
• Steroid-induced psychosis

External Links

• Psychiatry Case Report: Clarithromycin and Amoxicillin-Clavulanic Acid Induced Mania
• PubMed: Original Antibiomania Review (2002)