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Research project

ATHENA shingles study

Project overview

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. We want to do a larger study to find out if using amitriptyline when the rash first appears really prevents pain later.

The only way to find this out is by doing a clinical trial. We will recruit 846 people aged 50 years or older who have been diagnosed by their GP with shingles, within 144 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’re 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. 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. We have met with people with experience of shingles, with one person joining us as a co-applicant. We discussed the trial with them, and they identified potential barriers to taking part, such as lack of understanding about the condition; difficulty accessing GP appointments; and wrong information online about the risks of taking amitriptyline. While some people felt that any side-effects were offset by the potential benefits, others wanted more information first. We have carefully considered and addressed these issues in the design of the trial. Patient and Public Involvement will be built into the study set-up, running and sharing of the results.

We are a group of researchers from three of the UK’s leading primary care research universities. We have expertise in pain, post-herpetic neuralgia and running clinical trials in GP surgeries on skin problems and infections. We are uniquely placed to run the trial that is needed to answer the long-standing and important question of whether early use of amitriptyline in shingles prevents long-term pain.

Study team:
University of Southampton: Co-CI Professor Hazel Everitt, Professor Felicity Bishop
University of Bristol: Professor Matthew Ridd


Lead researcher

Professor Hazel Everitt

Professor of Primary Care Research

Research interests

  • Supporting Self-management 
  • Healthcare communication
  • Development of digital interventions
Connect with Hazel

Collaborating research institutes, centres and groups

Research outputs