Antidepressants

With Professor Tamar Pincus, Dr Hollie Birkinshaw, Dr Cathy Price and Ian Taverner

• Tamar is Professor in Health Psychology at the University of Southampton

• Hollie is a Research Fellow at the University of Southampton

• Cathy is a Consultant in Pain Medicine at University Hospital Southampton

• Ian is Chair of the Consortium to Research Individual, Interpersonal and Social Influences in Pain (CRIISP)

This information was last updated in June 2025. It is due for a review in June 2028.

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What are antidepressants?

Antidepressants are a group of medications that were originally developed to treat depression. They work by increasing some of the chemicals in the brain, particularly one called serotonin. As serotonin is thought to affect both mood and pain, antidepressants are now also prescribed for lots of other health conditions, including chronic pain. 

Antidepressants are grouped into categories. The most common categories are: 

• selective serotonin reuptake inhibitors (SSRIs)
• tricyclic antidepressants (TCAs) 
• serotonin-noradrenalin reuptake inhibitors (SNRIs)

Why are antidepressants used to help people manage chronic pain?

Research suggests that antidepressants may be useful for treating pain because the same chemicals that affect mood might also affect pain. There are certain categories of antidepressants that are used to manage chronic pain. 

You may have heard of amitriptyline (which is a TCA) or duloxetine (which is an SNRI). These drugs are now used to treat a variety of chronic pain conditions, such as fibromyalgia and nerve damage due to diabetes. They have been used in this way for many years. 

How are antidepressants thought to work?

Antidepressants may help treat pain in several ways. Most work by increasing serotonin levels. 

Many people living with pain have difficulty sleeping. Some antidepressants can make you feel drowsy, so if they are taken at the right time, they may improve your sleep. Research shows that improved sleep can have a knock-on effect on improving pain and wellbeing. On the other hand, being drowsy can make it difficult to work, drive and get about. 

How effective are they?

A detailed Cochrane Library review of 176 research studies, including 28,664 people with chronic pain, found that in the short term more people were likely to experience pain relief when taking duloxetine compared with those taking a placebo. However, there is very little information on longer-term use. The research also suggested that there is no strong evidence available on the effectiveness of other antidepressants. This does not mean that they don’t work, it simply means that there is not yet any good evidence to show whether they do or don’t.

How should I take them?

It’s best to take antidepressants at the same time each day. You also need to take them regularly for them to have any effect. You usually start with a lower dose and build up slowly to the right dose for you, as you may experience side effects with higher doses. Swallow the medicine whole with a glass of water and do not try to split the tablet or capsule. 

What are the side effects? 

All antidepressants have side effects. Common side effects are headaches, drowsiness, sickness, dizziness, blurred vision and a dry mouth. These are more common with TCAs. If you have glaucoma or problems with your prostate, TCAs may make these worse. Duloxetine may raise your blood pressure. You may not experience all these side effects, or any at all. Side effects differ from person to person, and can be mild or severe. They are usually worse when you start taking a medication. 

What do they mix badly with?

Taking antidepressants with any other medication that also works to raise the levels of serotonin in the body, such as other antidepressants or tramadol (an opiate, used to reduce pain), can give you a condition called serotonin syndrome. Serotonin syndrome can make you feel shaky and agitated, and in some cases can cause fits. 

You should also avoid alcohol with certain antidepressants, as together they can make you feel drowsy and dizzy. 

It is really important to talk to your GP about any medications you are currently taking, and any other conditions or symptoms you have, before you decide to take antidepressants. Whenever you are offered a new medicine, always ask what it is for, what the side effects are, what will happen if you don’t take the medication and how it interacts with any other medicines you are already taking. 

What could I do instead of, or as well as, taking antidepressants?

There are many options for managing your pain, and it is important that you and your healthcare professional find the ones that are best for you. No two people are the same, and there is no known single cure or effective treatment for pain. 

You might want to start by using methods that have better evidence behind them or fewer side effects. These include physiotherapy, talking therapies such as cognitive behavioural therapy (CBT) or acceptance and commitment therapy (ACT), and techniques such as mindfulness, relaxation and positive self-talk. You can also do exercises to gradually build up your flexibility and strength. Your doctor might recommend pain management, which combines different approaches to improve your life with pain. 

How do I come off them?

If you are thinking of stopping taking your antidepressants, it is very important that you discuss this with your doctor because stopping taking them suddenly may cause unpleasant symptoms. This is especially important for people who might be taking antidepressants for pain, but also for mental-health issues. 

Many people struggle to come off antidepressants and there is no medicine you can easily replace them with to help you with this. The best advice is to reduce your antidepressant dose gradually, in line with your doctor’s instructions.