Amoxicillin-Clavulanic Acid and Depression
Amoxicillin-clavulanic acid (Clavulin) can potentially cause depression as a rare side effect, with approximately 1% of patients reporting depression during treatment. 1
Evidence on Antibiotic-Related Depression
Depressive disorders are classified as Category 1 (no restriction for use) in relation to combined hormonal contraceptives, with evidence showing that their use did not increase depressive symptoms in women with depression compared to baseline or non-users with depression 1
Depression was reported in approximately 1% of patients taking apremilast, prompting recommendations for appropriate discussion and patient counseling before therapy initiation to prevent worsening of pre-existing depression or suicidality 1
A case report documented the occurrence of manic episodes separately induced by both clarithromycin and amoxicillin-clavulanic acid in a 50-year-old man with no psychiatric history, who presented with psychiatric symptoms (logorrhea, elevated mood, irritability, increased physical activity, and delusions) shortly after antibiotic prescription 2
Mechanism of Action
Clavulanic acid has been shown to increase dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking, specifically by affecting proteins Munc18-1 and Rab4 that play critical roles in neurosecretion and vesicle trafficking 3
The brain-gut-microbiota axis has multiple sites for off-target antibiotic activity, which may produce either positive or negative effects on mental health 4
Antibiotics can bring about significant decreases in gut microbial diversity, which is viewed as a risk factor for depression 4
Risk Factors and Clinical Evidence
A nested case-control study found that treatment with a single antibiotic course was associated with higher risk for depression across all antibiotic groups, with an adjusted odds ratio of 1.23 for penicillins 5
The risk of depression increased with recurrent antibiotic exposures to 1.40 and 1.56 for 2-5 courses and >5 courses of penicillin, respectively 5
Similar associations were observed for anxiety, most prominently with exposures to penicillins and sulfonamides 5
Clinical Considerations
The most common adverse effects of amoxicillin-clavulanic acid are typically diarrhea, nausea, upper respiratory tract infections, and headache 1
In patients experiencing gastrointestinal adverse effects from antibiotics, 70% to 80% occurred within the first 2 weeks, 75% to 80% were mild in severity, and 60% to 65% resolved within the first month 1
When prescribing amoxicillin-clavulanic acid, monitor patients for changes in mood, particularly those with a history of depression or other psychiatric conditions 2, 4
Management Recommendations
If depression develops during treatment with amoxicillin-clavulanic acid, consider discontinuing the medication if clinically appropriate and switching to an alternative antibiotic 2
In the documented case report, psychiatric symptoms improved approximately 12 hours after clarithromycin cessation, and the patient was symptom-free 1 week after stopping amoxicillin-clavulanic acid 2
Early recognition and intervention for psychiatric side effects related to antibiotherapy can substantially influence the administered medical care and recovery 2
For patients with a history of depression who require amoxicillin-clavulanic acid therapy, consider closer monitoring for mood changes during treatment 4, 5