Antidepressants used for pain

Some antidepressants can also ease certain kinds of long-lasting (chronic) pain. Two groups are used most for back and neck pain: SNRIs (serotonin and norepinephrine reuptake inhibitors) and older medicines called tricyclic antidepressants.

Duloxetine (Cymbalta) is the SNRI studied most for pain. The FDA has approved it for chronic musculoskeletal pain, including chronic low back pain. Venlafaxine (Effexor XR), another SNRI, is sometimes used for pain “off-label,” meaning without FDA approval for that use.

Tricyclics such as amitriptyline and nortriptyline (Pamelor) are also used off-label for pain.

Being offered an antidepressant for pain does not mean anyone thinks your pain is imagined, or that you must be depressed. These medicines are used because they act on the body’s pain system.

Most of the research is on low back pain. Very few studies have looked at neck pain.

The brain and spinal cord have their own system for turning pain signals down, using chemical messengers such as serotonin and norepinephrine. Researchers think these medicines strengthen that system by raising those messengers, though much of what is known comes from animal studies.

The effect on pain seems to be largely separate from any effect on mood. In studies, people with depression did not get more pain relief than people without it.

For tricyclics, the doses used for pain are usually lower than the doses used for depression. Duloxetine is also approved to treat depression and anxiety, which some people live with alongside pain.

Starting

Your prescriber will ask about your other medicines, alcohol use, liver and kidney health, blood pressure, heart health, glaucoma, seizures, and any personal or family history of bipolar disorder.

Doses usually start low and go up slowly, to give your body time to adjust.

Some people notice a change within a couple of weeks, but judging the full effect usually takes several weeks.

While you take it

Nausea is the most common side effect of duloxetine. Starting low and going up slowly helps many people adjust. Tricyclics often cause drowsiness, which is one reason they are usually taken in the evening. Until you know how the medicine affects you, take extra care with driving or other tasks that need you to be alert.

Stopping

Stopping suddenly can cause discontinuation symptoms, such as dizziness, nausea, headache, irritability, tingling and nightmares. They are usually mild. One review estimated that, after allowing for symptoms people also get when stopping a placebo, about 1 in 6 or 7 people who stop get symptoms caused by stopping. Results varied a lot between studies, and a few people have severe symptoms. Some medicines, such as venlafaxine, cause them more often. Prescribers usually lower the dose gradually.

For long-lasting back pain, a large review found that SNRIs such as duloxetine lowered pain by about 5 points on a 0 to 100 scale over 3 months or less. That is a small effect, below what most people would notice. Daily function improved by a similarly small amount. [2]

An earlier review for the American College of Physicians also found modest benefits from duloxetine. Its guideline lists duloxetine as a second-line option for chronic low back pain, after nondrug treatments and anti-inflammatory pain relievers (NSAIDs). Guidelines in the US and UK disagree about using SNRIs for back pain.

Across many kinds of chronic pain, duloxetine has the most reliable evidence of any antidepressant. For most others, the evidence is uncertain. [4]

In combined studies, tricyclics did not clearly reduce back pain. One trial of low-dose amitriptyline for chronic low back pain found no clear pain benefit at 3 or 6 months, and only a small, short-lived gain in function. [2] [9]

Other antidepressants, such as sertraline (Zoloft) or fluoxetine (Prozac), have not helped back pain in the few studies done. [2] [7]

For sciatica, the evidence is too uncertain to say. A few small studies suggest tricyclics or SNRIs might help, but the results are not reliable. For pain down the arm from an irritated nerve in the neck, there is very little good research. [2] [15]

Little research has followed people for longer than 3 months. Averages hide a range. Some people get more relief than average and some get none, and studies cannot yet predict who will benefit.

Common with SNRIs

• Nausea, dry mouth, constipation or diarrhea.
• Sleepiness or trouble sleeping, tiredness and dizziness.
• Sweating.
• Sexual side effects, such as lower desire or trouble reaching orgasm.

In back pain and arthritis trials, about 6 in 10 people taking an SNRI had at least one side effect, compared with about 5 in 10 taking a placebo (dummy pill). About 1 in 8 stopped because of side effects, compared with about 1 in 20 on placebo.

Common with tricyclics

• Dry mouth, constipation, blurred vision and trouble passing urine.
• Drowsiness, and dizziness or light-headedness when standing up.

Less common

• Higher blood pressure with SNRIs, more so with venlafaxine at higher doses. Your clinician may check it.
• Easier bruising or bleeding with SNRIs, especially when combined with NSAIDs such as ibuprofen or naproxen, aspirin, or blood thinners.
• Low blood sodium, mainly in older adults and people who take water pills. It can cause headache, confusion, weakness and unsteadiness.

Rare but serious

• Suicidal thoughts. All antidepressants carry a boxed warning, the FDA’s strongest, about a higher risk of suicidal thoughts and behavior in children, teens and young adults under 25, especially when starting or changing the dose. In adults 25 and older, a large FDA review did not find this increase, and in people 65 and older the risk appeared lower.
• Serotonin syndrome, a rare but dangerous reaction that can happen when these medicines are combined with others that raise serotonin. Examples include tramadol (Ultram) and some other opioids, other antidepressants, the muscle relaxant cyclobenzaprine, migraine medicines called triptans, the cough medicine dextromethorphan, and St. John’s wort. They must not be combined with MAO inhibitors, a group that includes the antibiotic linezolid and some Parkinson’s medicines. Signs include agitation or confusion, a fast heartbeat, sweating, fever, and muscle twitching or stiffness.
• Liver injury is rare with duloxetine. It is usually not prescribed for people who drink alcohol heavily or have chronic liver disease.
• Tricyclics are far more dangerous in overdose than newer antidepressants, mainly because of heart rhythm problems, so prescribers take extra care when there is any risk of self-harm.

Older adults

Older adults taking any antidepressant have a higher risk of falls, especially alongside other medicines that cause drowsiness. Guidance for older adults advises avoiding amitriptyline and nortriptyline, because they can cause confusion, drowsiness and dizziness on standing.

Other downsides

• The average benefit for back pain is small, while side effects are common.

Get emergency care right away for thoughts of harming yourself, fainting, a very fast or irregular heartbeat, or signs of serotonin syndrome such as high fever, stiffness and confusion. In the US you can also call or text 988, the Suicide and Crisis Lifeline. Contact your clinician right away about worsening mood, new agitation or restlessness, or unusual changes in behavior. Call the same day about yellow skin or eyes, dark urine, or unusual bruising or bleeding.