Antidepressants And Your Liver

In this day and age we are becoming more and more aware of our mental health and how it can impact our lives. There is more awareness of, and more information available for, all sorts of mental health issues such as anxiety, panic attacks or depression. 

In this article we will explore the role of antidepressants and discuss any effect they may have on the liver. The liver is an important organ to consider while taking antidepressants because these medications have to pass through the liver in order to be metabolised (broken down) and excreted from the body.  While antidepressants play an important role in managing or preventing depression, they can also cause harm to our livers, especially if they are abused, not taken at the prescribed dosage, or taken for long periods of time. It is essential to find the perfect balance of antidepressants such that they help your depression, while leaving your liver unharmed. 

Types of Antidepressants 

SSRIs (selective serotonin reuptake inhibitors)

These are a common type of antidepressants which are used in the treatment of depression. In our bodies, our central nervous system is composed of neurons (nerve cells) which relay messages to each other via a type of messenger known as neurotransmitters. Serotonin is a type of neurotransmitter and it plays a vital role in maintaining many bodily functions, one of which includes maintaining happiness. The SSRIs prevent the reuptake of serotonin by neurons which increases the amount of serotonin available to relay messages. This increase is thought to boost a person's mood and thus, help depression. Some examples of SSRIs are: 

• Fluoxetine 
• Sertraline
• Citalopram 

Most SSRIs are metabolised by the liver enzymes before they can be excreted from the body. Each individual will metabolise SSRIs at a slightly different rate due to intrinsic genetic differences, but people who suffer from liver disease may not be able to take this medication. It has been observed¹ that SSRIs do carry the potential for hepatotoxicity (damage to the liver). 

SNRIs (serotonin-norepinephrine reuptake inhibitors)

This type of medication is also used in the treatment of depression. As suggested by the name, it prevents the reuptake by neurons of two neurotransmitters: serotonin and norepinephrine. Norepinephrine, also known as noradrenaline, is also a neurotransmitter which is used to regulate our mood. When the reuptake of these neurotransmitters is prevented, there are more of them available to relay messages between neurons, which can help improve your mood. Some examples of these include: 

• Levomilnacipran
• Desvenlafaxine
• Duloxetine

Unfortunately, these types of antidepressants can also cause hepatotoxicity, especially duloxetine.¹ The damage done to the liver by these antidepressants is often hard to predict, but can be reversible if you stop taking them. 

TCAs (Tricyclic Antidepressants)

This class of antidepressants work in a similar way to SNRIs; they stop the neurotransmitters, serotonin and norepinephrine, from being taken up by neurons.² TCAs have been used to treat depression for a long time but they have a lot of side effects which can limit their use. This is because they can affect other neurotransmitters in the brain as well as serotonin and norepinephrine. Some common TCAs used are:

• Nortriptyline
• Amitriptyline 
• Amoxapine

TCAs, like other antidepressants, are broken down by liver enzymes. It has been observed that TCAs can also cause liver toxicity. 

MAOIs (Monoamine Oxidase Inhibitors)

MAOIs were the first medication used in the treatment of depression. However, if you take these you need to avoid certain foods which can trigger an extreme rise in blood pressure if taken with this medication.³ Due to this and other major side effects, their use is now limited and newer medication with fewer side effects are being used. 

MAOIs work by inhibiting an enzyme known as monoamine oxidase. This enzyme usually removes serotonin, dopamine and norepinephrine from the brain and thus, its inhibition causes the level of these neurotransmitters to rise, which can boost mood. Some examples are:

• Selegiline 
• Isocarboxazid 
• Phenelzine 

MAOIs have a high potential of causing harm to the liver. In certain cases, they can even cause liver failure and fatality. 

Liver function and drug metabolism 

Your liver is located on the upper right hard part of your abdomen, just under your ribs. You cannot normally feel your liver but when a disorder causes it to enlarge, its edges can be felt. Its actual size relies on your height and weight but it is generally a large organ. It is also an essential organ as it is responsible for performing many body functions, such as:

• It acts as a filter and filters out unwanted substances from our blood, such as toxins and old red blood cells
• It breaks down (metabolises) large substances such as fats, proteins and carbohydrates into smaller substances. These smaller substances are easier and quicker for the body to absorb. It also metabolises drugs so that they can be removed by the body
• It helps to form bile; bile is then used to to help to digest fat
• It also makes certain substances which can help in blood clotting 
• It acts as storage for glycogen (a form of a sugar called glucose) and vitamins, for the body to use later when it is needed 

Any antidepressants that you take are metabolised in your liver. The drugs are broken down into smaller compounds which are less therapeutic and smaller in size, which makes it easier for the body to remove them. There are many chemical processes taking place in the liver and thus, there are many enzymes which help to carry out these processes. One such enzyme group are the cytochrome P450 enzymes.⁴ The P450 enzymes are extensively involved in the breakdown of antidepressants in the liver and they act as an accelerant (catalyst) for these chemical processes. 

There are several factors which can influence liver metabolism. These include

• Age
• Disorders that decrease blood flow through the liver (for example, shock, heart failure etc)
• Genetic impairment of any liver enzymes
• Alcohol, drugs, smoking
• Certain food such as grapefruit juice, which can inhibit cytochrome P450, and brussel sprouts which can enhance its activity

Since antidepressants are metabolised by the liver, it is important to assess liver function before prescribing this medication. If a person has a pre-existing liver disease, these antidepressants should be avoided as their metabolism by the liver will be hindered which could be harmful to the person who is taking them. 

Liver-related side effects of antidepressants

Hepatotoxicity: Hepatotoxicity is when the liver undergoes any damage to its structure or there is any impairment of its function. It is usually caused by substances such as drugs, alcohol, toxins and certain medication such as antidepressants. This condition needs to be treated as soon as possible, otherwise, it could lead to liver cirrhosis, liver failure and even death. Some common signs and symptoms you may experience are: 

• Pain in your upper right abdomen
• A yellow tinge to your skin and eyes (jaundice)
• Dark-coloured urine
• Clay-coloured stool
• Nausea and loss of appetite 

Drug-induced liver injury (DILI): in this condition, there is an injury to the liver due to some drugs. This is a common condition and the symptoms which you are experiencing can be reversed by simply stopping the medicine causing them. You are more likely to experience this, if you already have a pre-existing liver condition or if you are genetically more susceptible to it. Some drugs which might cause DILI are anticancer drugs, antibiotics, anaesthetics, and some heart medications.⁵ Antidepressants can also cause liver injury and some which carry a greater risk of this are phenelzine, iproniazid and nefazodone. Some symptoms of DILI are:

• Jaundice 
• Abdominal pain
• Fatigue
• Nausea and vomiting
• Itchy skin 

At times, fever and rash

Precautions and monitoring 

As antidepressants are known to cause liver injury, they must be used with caution, especially in those patients who have pre-existing liver diseases. Before starting any antidepressant, patients should be screened to test for these pre-existing conditions. A simple blood test – Liver Function Tests (LFTs) – can show any liver injury or disease that may be present.⁶ This blood test can also be used to monitor the liver during the course of taking the antidepressants and adjust the dosages accordingly. If these levels start to become abnormal you may have to immediately discontinue the medication. After you discontinue, your doctor might prescribe another antidepressant, which might suit you better. 

Summary

Depression is a common mental health condition and as awareness is increasing, these patients are encouraged to seek treatment for their depression by using antidepressants. SSRIs, SNRIs, MAOIs and TCAs are all examples of some common antidepressants that are used. Generally, they function by increasing the amount or effect of neurotransmitters such as norepinephrine and serotonin which can help to boost our mood and alleviate depression. These medications can be quite beneficial but they can also cause liver injury such as hepatotoxicity and DILI. 

The liver is a large and important organ in our body. It is responsible for filtering our blood of toxins and breaking down larger substances into smaller ones so that they can be easily excreted from the body. If the liver is damaged and unable to perform these vital functions, it can make us quite ill and sometimes, even be fatal.

 If this injury occurs, the antidepressants which are being taken need to be immediately stopped and replaced by another antidepressant. It is also recommended that patients should be screened for a pre-existing liver injury or damage before starting any antidepressants and the patients LFTs should be monitored every few months, in order to diagnose any injury to the liver.