Can Levofloxacin Cause Depression? A Comprehensive Look at Fluoroquinolone Side Effects

October 12, 2025 •

3 min read

In July 2018, the FDA updated its warnings for fluoroquinolone antibiotics, including levofloxacin, to include significant risks of mental health side effects. This warning highlights the potential for serious psychiatric reactions, such as confusion, agitation, hallucinations, and notably, depression, among other issues. These reactions can occur after just one dose and may be long-lasting or even permanent in some cases.

Quick Summary

Levofloxacin, a fluoroquinolone antibiotic, can cause psychiatric reactions, including depression, due to its effects on the central nervous system. This article explores the mechanisms behind these adverse effects, reviews regulatory warnings, and discusses patient monitoring and safety measures.

Key Points

Depression Risk: Levofloxacin can cause depression and other psychiatric side effects, as explicitly warned by the FDA.
Neurological Mechanism: The drug crosses the blood-brain barrier and can inhibit GABA receptors, leading to central nervous system (CNS) excitation.
Wide Range of Symptoms: Psychiatric side effects include anxiety, confusion, insomnia, hallucinations, and, rarely, suicidal thoughts or attempts.
Discontinue Immediately: If mental health changes occur, the medication must be stopped immediately and a doctor contacted to mitigate the risk of serious or long-lasting harm.
Appropriate Use: Levofloxacin and other fluoroquinolones should be reserved for life-threatening infections when safer alternatives are not an option, especially considering the potential for disabling and permanent side effects.
Risk Factors: While anyone can be affected, those with pre-existing CNS conditions or renal insufficiency may be more susceptible to neurotoxic effects.
Family Monitoring: Since some mood changes can be subtle, patients should inform family or friends so they can help monitor for unusual behavior or psychological shifts.

Understanding the Link Between Levofloxacin and Depression

Studies suggest a connection between fluoroquinolone antibiotics like levofloxacin and psychiatric side effects, including depression. Regulatory bodies such as the U.S. FDA and the UK's MHRA have issued warnings about these serious, though often considered uncommon, reactions. The risk is linked to how these medications affect the central nervous system (CNS) and disrupt neurochemical balance.

The Mechanism of Neurotoxicity

Fluoroquinolones can enter the brain and interfere with neurotransmitters. A key mechanism involves inhibiting gamma-aminobutyric acid (GABA) receptors. As the brain's main inhibitory neurotransmitter, reduced GABA activity can lead to CNS over-excitation, potentially causing anxiety, restlessness, insomnia, and depression.

Another factor is the interaction with excitatory N-methyl-D-aspartate (NMDA) receptors. By affecting the magnesium block of these receptors, levofloxacin can increase glutamatergic transmission. This combination of decreased inhibition and increased excitation can result in excitotoxicity, potentially harming neurons. This imbalance is believed to contribute to the neuropsychiatric side effects.

Psychiatric Side Effects of Fluoroquinolones

Levofloxacin and other fluoroquinolones can cause a range of psychiatric adverse effects. These may include:

Anxiety and agitation: Feelings of restlessness or nervousness.
Confusional states: Difficulty concentrating, disorientation, or memory issues.
Sleep disturbances: Insomnia or unusual dreams.
Hallucinations and paranoia: Less common but possible effects.
Suicidal thoughts: Severe cases may involve suicidal ideation, requiring immediate medical help.

These effects can occur in healthy individuals, though those with existing CNS conditions or kidney problems may face higher risks. Symptoms can appear quickly and may persist after the drug is stopped.

Regulatory Actions and Patient Safety

Due to the risk of serious adverse effects, including mental health issues, regulatory agencies have strengthened warnings for fluoroquinolones.

FDA Drug Safety Communications

The FDA has issued several warnings, requiring updated product labeling in 2018 to highlight mental health risks. The agency advises against using these drugs for less severe infections like acute bronchitis or uncomplicated UTIs when safer options are available, as the risks may outweigh the benefits.

Monitoring and Management

Healthcare providers should watch for psychiatric reactions during treatment. If mood changes, anxiety, or depression occur, the medication should be stopped right away. Patients should also inform family or friends about taking the medication so they can help recognize subtle changes.

What to Do If You Experience Symptoms

If you or someone you know develops mental health symptoms while on levofloxacin, stop the medication and contact a healthcare provider immediately. In cases of suicidal thoughts, seek emergency medical care. Prompt action can help resolve symptoms quickly.

Comparison of Fluoroquinolone Side Effects

While all fluoroquinolones have risks, the likelihood and severity of side effects can vary. An analysis of the FDA Adverse Event Reporting System (FAERS) database provides some comparative data.


Side Effect Category	Fluoroquinolones in General	Ciprofloxacin	Levofloxacin	Moxifloxacin
Psychiatric ADRs	Reported (7.75% of total ADRs)	Frequent, includes depression and suicidal ideation	Less frequent, but includes depression and suicidal ideation	Strong correlation with delirium
Tendon Problems	Well-documented risk	Most frequently associated	Documented risk, including tendon rupture	Risk present
Neuropathy (Nerve Damage)	Reported risk, potentially irreversible	Reported	Reported risk, including paresthesia	Risk present
Cardiac Effects	QT prolongation risk	Associated with QT prolongation	Documented risk of QT prolongation	Notable cardiotoxicity

Conclusion

In answer to the question, "Can levofloxacin cause depression?", the answer is a definite yes. As a member of the fluoroquinolone class of antibiotics, it carries risks of CNS side effects such as depression, anxiety, confusion, and other psychiatric issues. These risks have led to strong warnings from health authorities globally. The underlying mechanism involves the drug's interaction with GABA and NMDA receptors in the brain. Patients must be aware of these potential side effects and seek immediate medical help if any mental health changes occur during treatment. Healthcare providers should reserve fluoroquinolones for serious infections where the benefits outweigh the significant and potentially lasting risks.

Key Takeaways

FDA Warnings: Regulatory bodies warn that fluoroquinolones like levofloxacin can cause serious, potentially permanent mental health side effects, including depression and suicidal ideation.
CNS Mechanism: The drug can cross into the brain and block GABA receptors, disrupting the balance of brain chemicals and causing CNS excitation.
Immediate Discontinuation: If any psychiatric symptoms appear, such as depression, anxiety, or confusion, stop the medication immediately and contact a doctor.
Monitor for Symptoms: Patients and their families should watch for changes in mood or behavior.
Used with Caution: Due to significant risks, fluoroquinolones should be used only for severe, life-threatening infections when other options are unavailable.

Frequently Asked Questions

While depression is listed as an uncommon (0.1% to 1%) side effect in clinical data, its occurrence is serious enough to be included in strong warnings from regulatory agencies. Some psychiatric reactions are rare but can be severe.

The onset of psychiatric side effects can vary greatly. Some individuals have reported symptoms appearing shortly after the first dose, while in other cases, it may take several days. Immediate discontinuation is necessary at the first sign of a serious adverse reaction.

The proposed mechanism involves levofloxacin's ability to cross the blood-brain barrier and inhibit gamma-aminobutyric acid (GABA) receptors. This can lead to over-excitation of the central nervous system, which is believed to be the cause of the neuropsychiatric effects.

In some cases, the mental health side effects can resolve after stopping the medication, but regulatory warnings indicate that some individuals have experienced potentially irreversible and disabling side effects. The long-term effects can be difficult to predict.

You should stop taking levofloxacin and contact your doctor immediately. For severe symptoms like suicidal thoughts, seek emergency medical help right away.

According to the FDA, levofloxacin and other fluoroquinolones should generally be reserved for severe, life-threatening infections when other treatment options are not available. The risk of serious side effects outweighs the benefits for uncomplicated infections.

Yes, the psychiatric side effects are a risk associated with the entire class of fluoroquinolone antibiotics, including ciprofloxacin, moxifloxacin, and others. FDA warnings regarding mental health effects have been harmonized across the entire class.