ATHENA: AmiTritypline for the prevention of post-HErpetic NeuralgiA


National Institute for Health (NIHR) Health Technology Assessment (HTA) Ref. NIHR129720

What is the research question?

What is the effectiveness of prophylactic low-dose amitriptyline for the prevention of post-herpetic neuralgia in patients diagnosed with herpes zoster?

What is the problem?

Shingles is caused by the same virus that causes chickenpox. It “sleeps” in the nerve cells for decades. When it “wakes up”, it can make people feel generally unwell, cause tingling or pain in one part of the body, followed a few days later by a rash. The rash can take up to 4 weeks to heal. Antiviral medicine helps reduce initial pain and rash severity. Some people can have “nerve pain” months after the shingles rash has gone. Called post-herpetic neuralgia, we don’t have any treatments to prevent this. Patients buy, and GPs prescribe, painkillers such as paracetamol, but they often don’t help. Amitriptyline is an old medicine, originally used at high doses (75-150 mg) to treat depression but now used at low dose for nerve pain. A small study published in 1997 suggested that taking a low dose (25 mg) of amitriptyline early on may help prevent post-herpetic neuralgia.

What is the aim of the research?

We want to do a larger study to find out if using amitriptyline when the rash first appears really prevents pain later. If starting amitriptyline early on does help, it is a cheap medicine that would prevent prolonged, difficult-to-treat pain for thousands of people. However, amitriptyline commonly causes side-effects such as dizziness, dry mouth and constipation. It can also cause problems when used together with some other medications. This study is needed so we can be sure that any benefits outweigh any harms.

How will this be achieved?

We will recruit 846 people aged >50 years who have been diagnosed by their GP with shingles, within 72 hours of the rash appearing. We will ask everyone to take tablets nightly for 10 weeks: half will be given amitriptyline and the other half will get placebo (or “dummy”) tablets. Neither patients nor their doctors will be able to choose which group they are in. This will be done by a computerised process called “randomisation” – a bit like rolling a dice to decide. This way the results cannot be affected by anyone’s beliefs about amitriptyline. All other care will be the same – this includes GPs prescribing antivirals and painkillers if needed. We will use questionnaires to find out what happens to everyone over the following 12 months, especially whether they still have pain related to shingles at 3 months.

Who is leading the research?

Dr Matthew Ridd, GP and Reader in Primary Health Care, Population Health Sciences, University of Bristol.

Further information:

Dr Matthew Ridd

For more information or to get involved in this project, please contact

The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.