It’s a typical story heard around the UK and the world. Melissa (insert any name here) has lived with anxiety for as long as she can remember. As a child, it prevented her from making friends as she preferred to stay at home. As she grew older, it became worse, framing her as aloof and detached. Aged 20, she fell and fractured her knee badly. Four operations later, the pain hadn’t subsided, so her doctor prescribed her tramadol, an opioid pain medication.
The tramadol didn’t just help ease Melissa’s knee pain in the short term, for the first time it lifted her out of the fog of anxiety. In her own words, “It made me feel beautiful.” As her tolerance increased, Melissa started seeking out more tramadol. She lied to her doctor that she’d lost her prescription, she bought more from online pharmacies as well as from a drug dealer. She went from taking eight tablets a day to 90. She stopped eating and lost four stone in weight, “I didn’t care about my life much, I just wanted to feel calm.”
Opioids work by attaching to receptors across the body. They block pain messages sent from the source of the pain through the spinal cord to the brain whilst also creating feelings of well-being and euphoria. This story is becoming more and more common. Prescriptions for opioid-based painkillers have increased by more than 60 per cent in the past decade. Official statistics show tramadol was implicated in 220 drug-related deaths in England 2018 compared to just seven in 1998.
Oxycodone, the drug at the centre of the epidemic in America, was implicated in 79 deaths in England in 2018 compared to zero 10 years earlier. With this in mind, people are inevitably comparing the situation here with the epidemic across the pond. Let’s be clear, opioid prescribing is monitored much more closely in the UK than in the US, meaning the situation here is nowhere near as severe. But that doesn’t mean we should become complacent in the face of what is clearly a growing issue.
Addiction is a craving for a relief from suffering. It’s characterised by someone continuing their behaviour despite the negative consequences. This could be the gambler who applies for a payday loan to keep on betting or Melissa buying more and more tramadol at the expense of her health. Long-term opioid use is a way of papering over the cracks of a much deeper emotional problem. The search for that rush of pleasure is always likely to trump potential health complications.
Public Health England are currently reviewing practices around prescribing drugs. The government’s main tangible response so far has been introducing prominent health warnings on boxes of opioid painkillers. This might help to inform patients that the drugs are potentially addictive.
People who take prescribed or over-the-counter medicines containing opioids for non-cancer pain are now given stronger warnings about the risk of dependence and addiction. Healthcare professionals have been asked by the MHRA to discuss these warnings with any patient taking or planning to take an opioid-containing medicine. These discussions should also involve agreement of a treatment plan, including how long treatment should last, to minimize the risk of dependence.
Additional warnings are now to be added to the patient information leaflet to reinforce those warnings, making it clear that the medicine is an opioid, which can cause addiction, and that there can be withdrawal symptoms if people stop taking it suddenly. More information and warnings are provided throughout the leaflet.
Opioids have a serious risk of dependence and addiction, especially with long-term use. Following concerns raised about the prescribing rates of opioids in the UK, the Opioid Expert Working Group (EWG) of the Commission on Human Medicines (CHM) developed a set of recommendations to improve information for prescribers and patients and to protect public health. These recommendations were fully supported by CHM and formed the basis of the MHRA’s new warnings.
While the CHM continues to consider opioids as important and effective medicines in the treatment of short-term pain relief, they have advised against their long-term use in the treatment of non-cancer pain, due to the risk of dependence and addiction.
Opioid Expert Working Group
A University of Birmingham Professor is leading a national review into the benefits and risks of opioid medicines including issues around dependency and addiction. Opioids are a class of drugs including morphine and morphine-like drugs that are widely used as prescription pain relievers. Jamie Coleman, Professor of Clinical Pharmacology and Medical Education at the University of Birmingham’s Institute of Clinical Sciences, has been selected as Chair of the Opioid Expert Working Group of the UK’s Commission on Human Medicines.
The group met yesterday at the Medicines and Healthcare products Regulatory Agency (MHRA) to begin its comprehensive independent scientific review of all available evidence on the use of opioid medicines in the UK. Professor Coleman said: “In the United States there is a so-called ‘opioid crisis’ due to the increasing misuse of, and addiction to, opioids including prescription pain killers. “There is no evidence that there is a similar opioid addiction crisis in the UK, however, the use of opioid based medicines has gradually increased in Britain over the last decade or so”.
“The ultimate aim of this review is to provide clear information to healthcare professionals, patients and carers – no one should be unaware of the potential risks of opioid medicines. I am honoured to be part of this important piece of work and to be leading the Expert Working Group to ensure that information for patients and health professionals promotes best use whilst helping curb the over-prescription and misuse of these medicines in the UK.”
The group has now set out initial steps as to how it will conduct its review, drawing on best practice internationally. The review will:
- consider the current data on the utilisation of opioid-containing medicines in the UK, both prescribed and over the counter.
- examine whether the risk minimisation measures implemented for over the counter and prescription opioids have been effective or whether further measures are required.
- consider the benefit risk of opioid-containing medicines in particular for non-cancer indications, taking into account alternatives.
- make recommendations for regulatory action to better support appropriate use of prescription opioids, such as relevant changes to the Summary of Product Characteristics and Patient Information Leaflets, product labelling and packaging, and any other risk minimisation measures.
Dr June Raine, Director of MHRA’s Vigilance and Risk Management of Medicines (VRMM) Division, said: “Our highest priority is making sure the medicines you and your family take are safe and effective. In response to the growing concern internationally and in the UK about overuse and increased prescribing of opioid analgesics, we are seeking expert advice on the benefits and risks of opioid medicines, including best practice for risk minimisation. We will be listening to patients, stakeholders, and relevant experts, and working across the health sector to make sure the warnings on opioid medicines are consistent, clear, relevant and represent the known risks of tolerance and addiction”.
Codeine Review
The Medicines and Healthcare products Regulatory Agency (MHRA) is reviewing the sales, prescribing and misuse of codeine linctus to assess the impact of warning labels introduced in 2019. Responding to a freedom of information request submitted in April 2022, the MHRA said that it regularly monitors the safety of medicines and intends to review the impact of safety warnings in relation to the risk of addiction and dependence to opioids.
“As there are currently over 20 different opioids we will select a small and representative number of opioids to review in a phased approach,” the response said. “We are currently reviewing the benefits and risks of codeine linctus, which will include a review of sales, prescribing, and misuse over a number of years prior to labelling changes up to the current day. In line with usual practice, we will seek independent expert advice on this issue.”
The decision followed initial recommendations from the UK’s Commission on Human Medicines (CHM) opioid expert working group who advised that the label warning should appear prominently on the front of the medicine pack and should state “can cause addiction” and “contains opioid”.
Claire Anderson, president of the Royal Pharmaceutical Society (RPS), said that she welcomed the work of the opioid expert working group in reviewing the current benefits and risks of codeine linctus.
“Many community pharmacies decide not to stock this product due to the potential for misuse,” she said. “There are many other non-codeine based proprietary products on the market for the treatment of dry cough, which pharmacists and their teams are well placed to advise on”.
The UK Medicines and Healthcare Regulatory Agency (MHRA) has recognized the importance of assessing the benefits and risks of opioid medications, with the launch of an Opioid Expert Working Group. This group has already recommended that the labelling for opioid medicines must carry a warning that informs patients about the risk of addiction, which was accepted by the MHRA. The MHRA also announced that additional, strengthened warnings were to be added to the patient information leaflets of all opioids about the risk of dependence and addiction.
Opioid surveillance varies among countries; the majority of countries have systems in place to monitor prescription and over the counter opioids, as with all licensed medications. Monitoring often examines prescriptions issued, adverse drug reactions and deaths due to overdose. Spontaneous reporting is the most frequently used method for monitoring adverse drug reactions, which relies on physician and patient reporting and is known to be subject to under-reporting. In the United Kingdom, the yellow card system is used for capturing spontaneous reports,.
Despite encouraging steps in recognizing the importance of opioid surveillance in the United Kingdom, the arrival COVID-19 in 2020 may have impacted monitoring plans. For several months, the NHS cancelled nonurgent services in an attempt to avoid overwhelming the health service, due to the rapid increase in COVID-19 cases. While a return to some services occurred later in the year, it is unclear how those using opioids (illicit or prescribed) were affected. In addition, with such an intense focus on COVID-19, there remains a risk that opioid surveillance has been put to one side during the pandemic. Consequently, the aim of this review was to determine the impact of the COVID-19 pandemic on safety and surveillance of opioids in the United Kingdom.
As this review continues, labelling of opioids will continue to change. Pharmaceutical companies, as well as labelling manufacturers will have to continue to monitor the situation in order to keep their labels within the guidelines as they change.
