Fluoxetine, commonly known as Prozac, is a widely prescribed selective serotonin reuptake inhibitor (SSRI) used to treat depression, obsessive-compulsive disorder, and bulimia nervosa in the UK. Whilst fluoxetine is generally well-tolerated, questions occasionally arise about whether it can cause fatty liver disease. Current evidence does not establish a direct causal link between fluoxetine and fatty liver (hepatic steatosis), though the medication can occasionally affect liver function in other ways, such as elevated liver enzymes or hepatitis. Understanding the relationship between fluoxetine and liver health is important for patients and clinicians alike, particularly for those with pre-existing liver conditions or risk factors.
Summary: There is currently no established direct causal link between fluoxetine and the development of fatty liver disease (hepatic steatosis) in published literature and regulatory data.
- Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) metabolised primarily in the liver by cytochrome P450 enzymes, particularly CYP2D6.
- Documented hepatic reactions to fluoxetine include elevated liver enzymes, hepatitis, and cholestatic injury, though serious liver injury remains rare.
- Patients with pre-existing liver disease, those taking multiple medications, or consuming alcohol above recommended limits face increased risk of liver complications.
- Symptoms suggesting liver problems include jaundice, persistent nausea, dark urine, abdominal pain, or unexplained itching and warrant prompt GP assessment.
- Routine liver function monitoring is not standard for SSRIs, but liver function tests should be considered if symptoms develop or in patients with known risk factors.
- Significant liver enzyme elevations (ALT/AST >3× upper limit of normal with symptoms) require stopping fluoxetine and specialist referral.
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What Is Fluoxetine and How Does It Work?
Fluoxetine is a widely prescribed antidepressant belonging to the class of medications known as selective serotonin reuptake inhibitors (SSRIs). In the UK, it is commonly dispensed under the brand name Prozac, though generic versions are also available. Fluoxetine is licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of major depressive disorder, obsessive-compulsive disorder (OCD), and bulimia nervosa in adults. It is also licensed for moderate to severe major depressive episodes in children and young people aged 8 years and above when psychological therapies have been ineffective.
The medication works by selectively inhibiting the reuptake of serotonin in the brain. Serotonin is a neurotransmitter that plays a crucial role in regulating mood, emotion, and sleep. By blocking its reabsorption into nerve cells, fluoxetine increases the availability of serotonin in the synaptic space between neurones, thereby enhancing serotonergic neurotransmission. This mechanism helps to alleviate symptoms of depression and anxiety over time, typically requiring several weeks of consistent use before therapeutic benefits become apparent.
Fluoxetine is metabolised primarily in the liver by the cytochrome P450 enzyme system, particularly CYP2D6, with contributions from CYP2C9, CYP2C19, and CYP3A4. Importantly, fluoxetine is a potent inhibitor of CYP2D6, which means it can affect the metabolism of other medications processed by this enzyme, potentially leading to drug interactions. Fluoxetine has a notably long half-life compared to other SSRIs—approximately 4 to 6 days for fluoxetine itself, and 4 to 16 days for its active metabolite, norfluoxetine. This extended duration means the drug remains in the body for several weeks after discontinuation, which can reduce the likelihood of withdrawal symptoms but also requires consideration when switching to other medications. For example, at least 5 weeks should elapse after stopping fluoxetine before starting a monoamine oxidase inhibitor (MAOI) due to the risk of serious interactions.
In patients with hepatic impairment, the Summary of Product Characteristics (SmPC) recommends a lower dose or less frequent dosing to account for reduced drug clearance. While fluoxetine is generally well-tolerated, like all medications, it carries potential side effects. Common adverse effects include nausea, headache, insomnia, and sexual dysfunction. Rare hepatic reactions, including elevated liver enzymes, hepatitis, and cholestasis, are listed in the SmPC. Understanding how fluoxetine is processed by the liver is important when considering its potential impact on hepatic health.
References: MHRA/EMC SmPC for fluoxetine (Prozac); NHS medicine page: Fluoxetine; BNF monograph for fluoxetine.
Recognising Liver Problems While Taking Fluoxetine
Liver-related adverse effects associated with fluoxetine are uncommon but have been documented in clinical literature and post-marketing surveillance data. The MHRA and the European Medicines Agency (EMA) acknowledge that SSRIs, including fluoxetine, can occasionally cause hepatotoxicity, though serious liver injury remains rare. It is important to note that there is currently no established direct causal link between fluoxetine and the development of fatty liver disease (hepatic steatosis) specifically in the published literature and regulatory data, though the medication can affect liver function in other ways.
Reported hepatic reactions to fluoxetine, as listed in the SmPC, include:
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Elevated liver enzymes (transaminases such as ALT and AST)
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Hepatitis (inflammation of the liver)
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Cholestatic injury (impaired bile flow)
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Idiosyncratic drug-induced liver injury (DILI) (unpredictable reactions)
These reactions typically occur within weeks to months of starting treatment, though they can develop at any time. Most cases are mild and reversible upon discontinuation of the medication. Routine liver function monitoring is not standard practice for patients taking SSRIs; however, liver function tests (LFTs) should be considered if symptoms develop or in patients with known risk factors or pre-existing liver disease.
Symptoms that may indicate liver problems include:
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Persistent nausea or loss of appetite
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Unusual fatigue or weakness
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Yellowing of the skin or whites of the eyes (jaundice)
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Dark urine or pale stools
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Abdominal pain, particularly in the upper right quadrant
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Unexplained itching (pruritus)
If you experience any of these symptoms while taking fluoxetine, it is essential to contact your GP promptly. Your doctor may arrange blood tests to assess liver function (LFTs) and determine whether the medication is contributing to your symptoms. Jaundice or persistent pruritus warrant urgent assessment, as they may indicate significant liver dysfunction.
For clinicians: If LFTs show ALT or AST greater than 3 times the upper limit of normal (ULN) with symptoms, or bilirubin greater than 2 times ULN, consider stopping fluoxetine and investigating for drug-induced liver injury (DILI). Hy's law criteria (transaminase elevation >3× ULN plus bilirubin >2× ULN) indicate a risk of serious hepatotoxicity and warrant immediate cessation and specialist referral.
In most instances, liver enzyme elevations are detected through symptom-prompted testing and resolve without causing lasting damage. However, early recognition and appropriate management are crucial to prevent progression to more serious hepatic complications.
References: MHRA/EMC SmPC for fluoxetine; NHS page: Fluoxetine – side effects; BSG guideline: Management of abnormal liver blood tests (2017); EASL/BSG DILI guidance.
Risk Factors for Liver Issues with Antidepressants
Certain individuals may be at increased risk of developing liver-related complications when taking fluoxetine or other antidepressants. Understanding these risk factors can help healthcare professionals and patients make informed decisions about treatment and monitoring strategies.
Pre-existing liver disease is the most significant risk factor. Patients with conditions such as:
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Non-alcoholic fatty liver disease (NAFLD)
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Alcoholic liver disease
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Chronic viral hepatitis (hepatitis B or C)
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Cirrhosis or significant hepatic fibrosis
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Autoimmune hepatitis
These individuals require careful consideration before initiating fluoxetine, as their compromised hepatic function may impair drug metabolism and increase susceptibility to further liver injury. NICE guidance recommends that antidepressants should be used cautiously in patients with hepatic impairment, with dose adjustments considered where appropriate. The SmPC advises a lower dose or less frequent dosing in hepatic impairment. Baseline and periodic liver function tests should be considered in patients with known liver disease or multiple risk factors.
Concurrent medications that are also metabolised by the liver or have hepatotoxic potential can increase risk through drug-drug interactions or additive hepatic stress. Because fluoxetine is a potent CYP2D6 inhibitor, it can increase plasma levels of other drugs metabolised by this enzyme (e.g., certain beta-blockers, antipsychotics, tricyclic antidepressants, and tamoxifen). Always check for interactions when prescribing or taking multiple medications. Other medications requiring caution include paracetamol in high doses, certain antibiotics, and some anticonvulsants. Polypharmacy—the use of multiple medications simultaneously—is an independent risk factor for drug-induced liver injury.
Alcohol consumption significantly increases the risk of liver problems. Alcohol itself is hepatotoxic, and when combined with medications metabolised by the liver, the risk of hepatic injury rises substantially. The UK Chief Medical Officers recommend that to keep health risks from alcohol low, it is safest not to drink more than 14 units per week on a regular basis, to spread drinking over 3 or more days, and to avoid binge drinking. Patients taking fluoxetine should be advised about these low-risk drinking guidelines.
Other risk factors include:
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Advanced age (over 65 years), as hepatic function naturally declines
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Obesity and metabolic syndrome, which are associated with fatty liver disease
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Genetic variations in drug-metabolising enzymes (though individual risk prediction is not yet routine)
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Female sex, which may be associated with increased susceptibility to certain forms of drug-induced liver injury in some studies
Patients with multiple risk factors should have baseline liver function tests considered before starting fluoxetine, with periodic monitoring during treatment as clinically indicated.
References: MHRA/EMC SmPC for fluoxetine; Specialist Pharmacy Service (SPS): Using antidepressants in liver impairment; GOV.UK UK Chief Medical Officers' low-risk drinking guidelines; BSG guideline: Management of abnormal liver blood tests (2017).
What to Do If You're Concerned About Your Liver Health
If you have concerns about your liver health while taking fluoxetine, do not stop the medication abruptly without medical guidance. Although fluoxetine's long half-life reduces the likelihood of withdrawal symptoms compared to other SSRIs, sudden discontinuation can still lead to adverse effects, and supervised cessation is essential. Instead, take the following steps:
Contact your GP or prescribing clinician to discuss your concerns. Be prepared to describe any symptoms you're experiencing, including their onset, duration, and severity. Your doctor will likely arrange blood tests to assess liver function (LFTs), which typically measure enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin levels. These tests can identify liver inflammation or dysfunction.
If liver function abnormalities are detected, your healthcare provider will consider several options:
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Continuing fluoxetine with monitoring if enzyme elevations are mild and asymptomatic
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Dose reduction to minimise hepatic stress
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Switching to an alternative antidepressant with a different metabolic profile
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Discontinuing fluoxetine if significant liver injury is suspected
For clinicians: Significant or persistent LFT derangement (e.g., ALT/AST >3× ULN with symptoms, or bilirubin >2× ULN) should prompt stopping the suspect drug and referral to hepatology or gastroenterology. Use the BSG guideline on management of abnormal liver blood tests and NICE NG49 for risk stratification (e.g., FIB-4 or Enhanced Liver Fibrosis [ELF] score) and referral pathways in patients with suspected NAFLD or fibrosis.
Further investigations may be warranted if liver abnormalities persist or worsen. These might include:
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Ultrasound scanning to assess liver structure and detect fatty infiltration
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Viral hepatitis screening
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Autoimmune liver disease markers
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Assessment for other causes of liver dysfunction
NICE recommends that patients with confirmed liver disease should be managed collaboratively, potentially involving hepatology specialists for complex cases.
Lifestyle modifications can support liver health regardless of medication use:
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Maintain a healthy weight through balanced diet and regular physical activity
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Follow UK Chief Medical Officers' low-risk drinking guidelines (≤14 units per week, spread over ≥3 days; avoid binge drinking)
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Ensure adequate hydration
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Avoid unnecessary medications or supplements that may stress the liver
When to seek urgent medical attention: If you develop jaundice, severe abdominal pain, persistent vomiting, confusion, or signs of bleeding (such as easy bruising or blood in vomit or stools), call 999 or attend A&E immediately if you are acutely unwell. Otherwise, contact your GP urgently or call NHS 111 for advice. These symptoms may indicate serious liver dysfunction requiring prompt intervention.
Reporting side effects: If you experience a suspected side effect from fluoxetine, you can report it via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or via the Yellow Card app. Reporting helps improve the safety of medicines for everyone.
Remember that while liver complications can occur with fluoxetine, they remain uncommon, and the medication provides significant benefits for many people with depression and other licensed conditions. Open communication with your healthcare team ensures that any potential issues are identified and managed appropriately whilst maintaining effective treatment for your mental health condition.
References: MHRA/EMC SmPC for fluoxetine; NHS urgent care advice (NHS 111/A&E pages); BSG guideline: Management of abnormal liver blood tests (2017); NICE NG49: Non-alcoholic fatty liver disease: assessment and management; MHRA Yellow Card scheme.
Frequently Asked Questions
Does fluoxetine directly cause fatty liver disease?
No, there is currently no established direct causal link between fluoxetine and the development of fatty liver disease (hepatic steatosis) in published medical literature or regulatory data. Whilst fluoxetine can occasionally affect liver function through elevated enzymes or hepatitis, these reactions differ from fatty liver infiltration and remain uncommon.
What liver problems can fluoxetine actually cause?
Fluoxetine can rarely cause elevated liver enzymes (transaminases), hepatitis (liver inflammation), cholestatic injury (impaired bile flow), and idiosyncratic drug-induced liver injury. Most cases are mild and reversible upon stopping the medication, though serious liver injury remains very uncommon.
Should I have my liver checked before starting fluoxetine?
Routine liver function monitoring is not standard practice before starting fluoxetine for most patients. However, baseline liver function tests should be considered if you have pre-existing liver disease, take multiple medications, consume alcohol regularly, or have other risk factors for hepatic complications.
Can I take fluoxetine if I already have non-alcoholic fatty liver disease?
Fluoxetine can be used cautiously in patients with non-alcoholic fatty liver disease (NAFLD), but requires careful consideration and potentially dose adjustment. Your GP should assess the severity of your liver condition and may arrange baseline liver function tests with periodic monitoring during treatment to ensure the medication is tolerated safely.
What are the warning signs of liver damage from antidepressants?
Warning signs include yellowing of the skin or eyes (jaundice), persistent nausea or loss of appetite, unusual fatigue, dark urine, pale stools, upper right abdominal pain, or unexplained itching. If you experience any of these symptoms whilst taking fluoxetine, contact your GP promptly for assessment and liver function tests.
What should I do if I'm worried about my liver whilst on fluoxetine?
Do not stop fluoxetine abruptly without medical guidance—contact your GP to discuss your concerns. Your doctor will likely arrange blood tests to check liver function and may continue monitoring, adjust your dose, switch to an alternative antidepressant, or discontinue fluoxetine depending on the results and your symptoms.
The health-related content published on this site is based on credible scientific sources and is periodically reviewed to ensure accuracy and relevance. Although we aim to reflect the most current medical knowledge, the material is meant for general education and awareness only.
The information on this site is not a substitute for professional medical advice. For any health concerns, please speak with a qualified medical professional. By using this information, you acknowledge responsibility for any decisions made and understand we are not liable for any consequences that may result.
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