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Antidepressants for Pain

Some pains, particularly arising from nerve damage or abnormal nerve function (neuropathic) and some muscle pains, often have limited response to normal painkilling drugs but can respond well to other groups of drugs, one of which is the older fashioned antidepressants.  This is by a direct effect on the mechanisms of the pain, and not through any effect on mood.  It is important to stress that the use of these drugs does not in any way imply that the pain is psychological or “in your head”.

The group of antidepressant drugs that most often help pain are called Tricyclics.  These include amitriptyline and nortriptyline.  Many of the other groups of antidepressants, notably the newer ones acting purely on Serotonin (SSRI’s) such as paroxetine, fluoxetine and similar drugs, do not work well for pain although they can be effective for depression.  Some other drugs acting on combinations of chemicals in the brain, such as duloxetine or maprotiline, can also be beneficial for pain.

Tricyclics work by blocking the re-uptake of chemical messengers called Noradrenaline and Serotonin (5-HT) into the nerve endings and therefore increasing their levels in the pain control pathways.  This is similar to the mechanism by which they help depression: however, they often give pain relief at far lower doses than are required for depression.   

They give benefit for pain in a number of different ways: both by their direct effect on pain, and also through beneficial effects on sleep.  Tricyclics are used for pain at a considerably lower dose than that for depression, and we would normally commence amitriptyline at the smallest tablet dose of 10mg, and it is usually used in a single daily dose at bedtime.

The use of antidepressants, while extremely well-established and supported by strong research evidence and experience, is outside the product licence for most of these drugs.  This is further discussed here.

The Faculty of Pain Medicine of the Royal College of Anaesthetists, together with the British Pain Society, has recently produced information sheets for patients that you may find helpful, on Amitriptyline, Nortriptyline and Duloxetine.


For the overall pathway that is suggested for nerve pain treatment, and how the antidepressants fit into this, follow this link The British Pain Society / Map of Medicine Neuropathic Pain pathway will also give useful information.

Side effects

Although at high doses these drugs have a number of  side effects, at the doses we use for pain these are less common.  Ones such as drowsiness are generally short term.  You need to be aware that they can also have an effect on reaction time and that this may affect your ability to drive safely.  They may interact with alcohol, and you should avoid drinking alcohol while taking these drugs.  They may also cause a dry mouth and, less commonly, blurred vision, constipation and weight gain. 

Their beneficial effects for pain take a few days to become established, and any initial drowsiness tends also to settle in a few days.  It is therefore well worth persisting with their use for at least a week or two before assessing whether or not they have worked.

We normally suggest that these drugs are started at a weekend or when possible drowsiness for the first couple of days will be less important.  It is best to take them  early in the evening to aid sleep and to avoid drowsiness the following day.

Sometimes amitriptyline, despite all this, can give unacceptable side-effects.  There are other drugs in this group, such as nortriptyline, which may be better tolerated and therefore worth trying.

Further information for professionals

Further reading



Gloucestershire Joint Formulary website










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Pain Service Website, Gloucestershire Hospitals NHS Foundation Trust
Webmaster Dr J G de Courcy, Consultant in Pain Medicine and Anaesthesia
email: pain.webmaster[at]

Page updated 19/02/2016