What antibiotics have psychiatric side effects?

October 12, 2025 •

4 min read

Studies of adverse drug reaction reports show that for individual antibiotics, the prevalence of psychosis ranges from 0.3% to 3.8% [1.2.1, 1.2.2, 1.2.3]. This article answers the question, 'What antibiotics have psychiatric side effects?', by detailing the specific drug classes, symptoms, and risk factors involved.

Quick Summary

Numerous antibiotics, including common classes like fluoroquinolones, penicillins, and macrolides, can cause a range of psychiatric side effects. Symptoms may include anxiety, delirium, psychosis, and mania.

Key Points

Prevalence: The prevalence of psychosis as an adverse drug reaction to antibiotics ranges from 0.3% to 3.8% [1.2.1, 1.2.3].
Key Culprits: Fluoroquinolones, macrolides (especially clarithromycin), beta-lactams, and metronidazole are classes frequently associated with psychiatric side effects [1.3.2, 1.3.5].
Symptom Spectrum: Symptoms can range from anxiety and insomnia to severe conditions like psychosis, mania, delirium, and suicidal ideation [1.2.4, 1.4.4].
Mechanisms: A primary proposed mechanism is the antagonism of inhibitory GABA-A receptors, leading to increased central nervous system excitability [1.5.2, 1.8.1].
Risk Factors: Key risk factors include advanced age, renal impairment, high antibiotic doses, and pre-existing central nervous system or psychiatric conditions [1.9.1, 1.8.1].
Management: The main treatment is discontinuation of the offending antibiotic, which usually leads to resolution of symptoms [1.10.4].
Misdiagnosis: These adverse effects are often underrecognized and can be misdiagnosed as primary psychiatric disorders [1.2.2].

Introduction to Antibiotic-Associated Neuropsychiatric Effects

While antibiotics are essential for fighting bacterial infections, they are also associated with a spectrum of neurological and psychiatric side effects [1.2.4]. These reactions, often termed antibiotic-associated encephalopathy (AAE), can range from mild symptoms like dizziness and anxiety to severe conditions like delirium, psychosis, and seizures [1.11.2, 1.11.4]. The prevalence of psychosis as an adverse reaction to antibiotics is estimated to be between 0.3% and 3.8% [1.2.1]. Due to symptom overlap with other neuropsychiatric conditions, these side effects may be underdiagnosed or misdiagnosed [1.2.2]. Symptoms typically arise within days of starting an antibiotic and often resolve after discontinuing the offending drug [1.10.4, 1.11.2].

Antibiotic Classes and Their Psychiatric Side Effects

Several classes of antibiotics have been documented to cause psychiatric adverse events. The risk and type of symptoms can vary significantly between classes and even between individual drugs within the same class [1.2.1].

Fluoroquinolones

This class includes drugs like ciprofloxacin, levofloxacin, and moxifloxacin [1.3.3]. They are frequently associated with neuropsychiatric side effects due to their ability to penetrate the blood-brain barrier [1.4.3].

Symptoms: Psychosis, confusion, delirium, anxiety, depression, suicidal thoughts, insomnia, and hallucinations are commonly reported [1.4.1, 1.4.4, 1.4.5]. The FDA has issued warnings about these risks, advising that psychiatric reactions can occur even after the first dose [1.3.3].
Mechanism: Fluoroquinolones are thought to cause neurotoxicity by antagonizing GABA-A receptors (an inhibitory neurotransmitter) and activating NMDA receptors (an excitatory neurotransmitter), leading to increased neuronal excitability [1.4.3, 1.8.2].

Beta-Lactams (Penicillins, Cephalosporins, Carbapenems)

This is a very broad class of widely used antibiotics.

Penicillins (e.g., amoxicillin, penicillin G): Associated with a range of effects from behavioral changes to psychosis and seizures [1.6.2]. Procaine penicillin, in particular, has been linked to psychosis [1.11.2].
Cephalosporins (e.g., cephalexin, cefepime): Neurotoxicity can manifest as confusion, altered mental status, encephalopathy, and seizures [1.5.3, 1.5.5]. The risk is notably higher in patients with renal impairment [1.5.3].
Carbapenems (e.g., imipenem, meropenem): Primarily associated with seizures, but also confusion and encephalopathy [1.5.2, 1.6.2].
Mechanism: The beta-lactam ring structure is similar to the GABA antagonist bicuculline. These antibiotics are believed to competitively inhibit GABA-A receptors, leading to CNS excitation [1.5.2, 1.8.1].

Macrolides

This class includes clarithromycin, azithromycin, and erythromycin. Of these, clarithromycin is most frequently linked to psychiatric side effects [1.6.1, 1.6.2].

Symptoms: Mania (sometimes called 'antibiomania'), delirium, acute psychosis, hallucinations, and insomnia have been reported [1.6.1, 1.6.2]. One study found clarithromycin had the highest risk for psychotic symptoms among all antibiotics studied [1.2.2].
Mechanism: The exact mechanism is unclear but may involve GABA-A antagonism, interactions with other drugs via CYP3A4 enzyme inhibition, or effects on cortisol metabolism [1.2.3, 1.8.4].

Other Notable Antibiotics

Metronidazole: This antibiotic can readily cross the blood-brain barrier and has been linked to encephalopathy, psychosis, confusion, seizures, and cerebellar dysfunction [1.7.2, 1.11.1]. The risk increases with prolonged use and high doses [1.7.2, 1.8.4]. The mechanism may involve GABA receptor inhibition and oxidative stress [1.6.2, 1.8.2].
Sulfonamides (e.g., sulfamethoxazole/trimethoprim): Associated with psychosis, delirium, and aseptic meningitis [1.6.2, 1.6.3].
Tetracyclines (e.g., doxycycline, minocycline): While minocycline has been studied for potential antipsychotic benefits, doxycycline has been associated with a significantly increased odds of psychosis [1.2.3].

Comparison of Antibiotics with Psychiatric Side Effects


Antibiotic Class	Common Examples	Common Psychiatric Side Effects	Proposed Mechanism
Fluoroquinolones	Ciprofloxacin, Levofloxacin	Psychosis, anxiety, depression, delirium, suicidal ideation [1.4.4]	GABA-A antagonism, NMDA receptor activation [1.4.3]
Beta-Lactams	Amoxicillin, Cefepime, Imipenem	Encephalopathy, seizures, confusion, psychosis [1.5.2, 1.5.5]	GABA-A antagonism [1.5.2]
Macrolides	Clarithromycin, Azithromycin	Mania, delirium, psychosis, hallucinations [1.6.1]	GABA-A antagonism, drug interactions (CYP3A4) [1.2.3, 1.8.4]
Nitroimidazoles	Metronidazole	Encephalopathy, psychosis, confusion, seizures [1.7.2, 1.11.1]	GABA receptor inhibition, oxidative stress [1.6.2, 1.8.2]
Sulfonamides	Sulfamethoxazole/Trimethoprim	Delirium, psychosis, aseptic meningitis [1.6.2]	Folate pathway interference, neuroinflammation [1.6.2]

Risk Factors for Developing Psychiatric Side Effects

Not everyone who takes these antibiotics will experience neuropsychiatric symptoms. Certain factors increase a patient's vulnerability:

Advanced Age: Elderly patients are at a higher risk [1.8.1, 1.9.1].
Renal Impairment: Kidney problems can lead to antibiotic accumulation, increasing the risk of toxicity, especially with beta-lactams and cephalosporins [1.5.3, 1.8.1].
Pre-existing CNS Conditions: A history of seizures, brain lesions, or other central nervous system disorders can predispose individuals to these side effects [1.5.3, 1.8.1].
Prior Psychiatric History: Patients with existing psychiatric disorders may be more susceptible [1.6.2, 1.9.1].
High Doses or IV Administration: Higher concentrations of the drug increase the likelihood of adverse events [1.9.1].

Management and Conclusion

The primary step in managing antibiotic-induced psychiatric symptoms is to discontinue the suspected antibiotic, if clinically feasible [1.10.4]. In most cases, symptoms resolve within a few days to a week after stopping the medication [1.10.2, 1.11.4]. In severe cases, such as acute psychosis or significant agitation, short-term treatment with antipsychotic or anti-anxiety medications may be necessary [1.10.1, 1.10.2]. It is crucial for both clinicians and patients to be aware that psychiatric symptoms can be a direct result of antibiotic therapy. Prompt recognition can prevent misdiagnosis and lead to a quicker recovery [1.2.2].

Authoritative Link: For more detailed information, consult the National Institutes of Health (NIH) article on Antibiotic-induced neuropsychiatric toxicity [1.2.2].

Frequently Asked Questions

Studies analyzing the FDA Adverse Event Reporting System (FAERS) have found that the macrolide antibiotic clarithromycin has the highest odds of being associated with psychosis adverse drug reactions compared to other antibiotics [1.2.2, 1.2.3].

Yes, penicillins, including amoxicillin, are beta-lactam antibiotics that have been associated with psychiatric side effects such as psychosis, confusion, and encephalopathy [1.3.2, 1.6.2]. This is thought to be due to their antagonistic effect on GABA-A receptors in the brain [1.5.2].

Psychiatric side effects from antibiotics, such as those from fluoroquinolones or cephalosporins, can appear within days of starting the medication [1.11.2]. For some drugs like ciprofloxacin, psychiatric reactions have been reported after the very first dose [1.3.3].

In most cases, antibiotic-induced neuropsychiatric side effects are reversible and resolve after the offending drug is discontinued [1.4.2, 1.10.4]. Symptoms typically resolve within a median of 5 days after stopping the antibiotic [1.11.4].

If you experience distressing mood changes, confusion, hallucinations, or other psychiatric symptoms while taking an antibiotic, you should contact your healthcare provider immediately. Treatment often involves stopping the medication and, if needed, short-term management of the symptoms [1.3.3, 1.10.4].

The main risk factors include advanced age, renal insufficiency (kidney problems), pre-existing central nervous system diseases (like epilepsy), prior psychiatric history, and the use of high antibiotic doses or intravenous administration [1.9.1, 1.8.1].

No, the risk varies significantly by antibiotic class and the specific drug. For example, fluoroquinolones and clarithromycin are reported to have a higher risk for psychosis, while some other antibiotics have a much lower association [1.2.1, 1.2.3].