Opiate pain killers and addiction in sickle cell disease

I have been prompted to write this blog, about one of the most difficult and contentious issues in sickle cell, having been to a conference at the Royal Society of Medicine on “Chronic Pain and Opiate Addiction”. Drug addiction is rightly one of the things that people with sickle cell worry most about and I hope that this blog will give you some background information and help put the risks into some sort of perspective for you.

Pain is a universal human experience and for sickle cell, of course, it is a defining feature of the disease; the relief of pain has always been one of the most important functions of medicine and for over 3,000 years opiate drugs have been the mainstay of pain relief. Opium is derived from the latex-like solution, which oozes from the unripe seed heads of the opium poppy when the surface is cut. It was known as a magical drug to the original civilisations of Mesopotamia (modern day Iraq) as well as to the ancient Egyptians, and in 500 BC Hippocrates, the Greek father of medicine, was the first to formally describe it’s pain killing properties. Despite being widely used from China to the Middle East there is little evidence for it being available in western Europe until the sixteenth century when Paracelsus, a Swiss physician, produced an alcoholic solution of opium, which he called laudanum, and which proved easy to administer and use. Morphine, the prototype opiate drug, was first extracted from raw opium in 1804 by Dr Frederich Serturner, who had been frustrated by the variable pain relief provided by different batches of opium. He named the drug after the Greek God of Dreams, Morpheus, reflecting it’s ability to induce drowsiness and euphoria, a feeling of “warm happiness” as well as pain relief. Codeine was synthesised later in 1830 and heroin or diamorphine in 1874.

For the relief of severe, acute pain morphine remains the “gold standard” pain killer and is one of the most important medicines in the doctor’s toolbox. In addition to morphine there are now a large number of different opiate drugs, which vary in potency or strength and in their side effect profile. However, they all work in the same way by attaching to receptors in the brain and suppressing the perception of pain. You will be familiar with many of these drugs which include, codeine phosphate, dihydrocodeine, oxycodone, buprenorphine, tramadol, fentanyl, pethidine, diamorphine and methadone.

Like all drugs, opiates have side effects including, nausea and vomiting, constipation, itching, sleepiness and slowing of the breathing rate or respiratory depression. These side effects can limit the use of the drugs, although over the years we have learnt to manage them more successfully. But the use of opiates is also complicated by some unusual side effects, which still impose significant restrictions on their use and which it is important to understand. These unusual side effects are related to the way that opiates work in the brain, they are tolerance, dependence, hyperalgesia and addiction. These confusing terms are often used inaccurately and I wanted to spend some time defining them and discussing what they mean to you. These problems can effect anyone treated with any of the opiate drugs, but as someone with sickle cell you are bound to be exposed to them on many occasions to manage your pain and it is as well to understand how they work and what the problems are.

Tolerance is a phenomenon which occurs after you have been taking any opiate for a period of time to control pain. The original dose of the drug becomes ineffective and the dose has to be steadily increased to maintain pain control. This happens even though there appears to have been no worsening in the severity of the pain. The body has become “tolerant” to the drug and more of the drug has to be given to produce the desired effect.

For a patient with a prolonged sickle cell crisis having to increase the dose of pain killers when they should be getting better can be a depressing scenario and it can seem as if the crisis is deteriorating. In reality, it is not that the crisis is getting worse, but that tolerance is developing to the opiate pain killers. It is important for the doctor looking after you to recognise this as well. They must decide whether it is time to change to a different form of pain relief, using drugs which do not display tolerance, or whether it is appropriate to continue to prescribe opiates at higher doses.

Dependence is a more frightening experience. All opiate drugs induce a state of physical dependency, even if they have only been taken for a short while. This state of dependency only becomes obvious when the opiates are stopped. At that point the patient has a “withdrawal syndrome”, which is best thought of as the body re-adjusting it’s biochemistry to working in an opiate free environment. Withdrawal episodes can be very alarming and upsetting. There are many symptoms which include, anxiety and depression, irritability, insomnia and restlessness, with irregular movements of the legs, yawning, hot and cold sweats with “goose bumps”, nausea, diarrhoea and stomach cramps. They start shortly after the opiates are stopped and can continue with gradually decreasing severity for as long as 1-2 weeks.

Physical dependency and withdrawal are major problems for people with sickle cell who receive opiates during a severe pain crisis. There are various ways of limiting the effects of dependency, which include prescribing opiates at the smallest dose and for the shortest period of time to achieve good pain control, and then gradually reducing the dose rather than suddenly stopping. None of these completely protects you from a withdrawal episode, which you often have to face on your own after you have been discharged from hospital.It is very important to recognise a withdrawal episode for what it is and you and your doctor should discuss this before you leave so that you know what the symptoms are and are prepared to work through it.

One of the great dangers for patients with sickle cell is that, as part of the withdrawal episode, some of you will have an upsurge of pain, which it is easy to confuse with recurrent sickle cell pain. If that happens then you can end up coming back into hospital and being treated with opiates again and again, in a vicious circle of admissions, for what is withdrawal pain rather than sickle cell pain. One way of distinguishing withdrawal pain from sickle cell pain is that it tends to be more widespread and diffuse and less easy to say exactly where you feel it, whereas with sickle pain you can usually pinpoint exactly the site of pain very easily. Also, the quality of the pain tends to be different with more of a burning feel to it, compared with the typical throbbing pain of a crisis. Think very carefully about any pain you develop after taking opiates; is it a new crisis or is it part of a withdrawal?  If it is part of a withdrawal a different approach is needed – taking more opiates is not the right answer.

Hyperalgesia refers to the tendency of opiate drugs to induce a state where even non-painful stimuli or sensations, such as simply touching someone’s skin, can be experienced as painful. At first sight this doesn’t make much sense, why should a pain killing drug increase your sensitivity to pain? However it is a fact and it can make using opiates for pain relief very complicated.

Hyperalgesia has obvious implications for someone with sickle cell. If a patient develops hyperalgesia, whilst they are being treated with opiates, they will feel and complain about having increasing pain and request more and more pain relief. The medically correct response is to reduce and stop the opiates, which will abolish the hyperalgesia. However this can be very difficult to do in the face of a distressed patient. In some ways this problem seems similar to tolerance. The difference is that in tolerance the original, “throbbing” sickle cell pain remains the problem, but with hyperalgesia the pain and distress is new and different in quality. This can sometimes allow the two to be distinguished; again it is important to think carefully about the pain you are experiencing and not assume that all the pain you feel is due to a sickle cell crisis.

Addiction as I said at the beginning, is the issue that worries patients the most when they are given opiate drugs, but in my experience, in contrast to the other problems we have discussed, addiction is a rare problem in the sickle cell community. Addiction implies that your whole life is consumed with a craving for the drug, whether it is alcohol, nicotine or morphine. A patient addicted to morphine will constantly plan how they are going to get further prescriptions of the drug, may lie about how much they have used and will hide away secret supplies in case they run out in future. The doses of morphine they take may escalate alarmingly and they will often take bigger doses than prescribed. In the end they may resort to criminal activity to guarantee supplies.

The bad news is that all opiate drugs have significant addictive potential and careless use of the drugs can result in addiction becoming established over a very short period of time. Recovery from addiction is slow and difficult and this is particularly the case in sickle cell disease. Because of recurrent severe pain episodes, patients with sickle cell may have no choice but to be treated with repeated courses of opiates, meaning that recovery from addiction and independence from opiates is seldom possible.

On the positive side, if opiates are used carefully and responsibly the risk of addiction is very small. They should only be used to treat severe, acute pain. The dose of opiates should be matched to the level of pain and only the minimum necessary dose for effective pain relief should be used, and finally, the opiates should be reduced and stopped as soon as the pain starts to improve. It is very important that doctors as well as patients understand these “good practice rules” and the reasons why it is so important they are adhered to. The danger arises when opiates are used over prolonged periods of time, in inappropriately large doses and courses of treatment are repeated frequently at short intervals. There also seem to be particular groups of individuals who are most at risk of addiction these include, patients with a history of depression or other mental health disorders and those who already show addictive behaviour with other substances, such as alcohol or illegal drugs. It is important that doctors and patients are especially careful when using opiates to treat sickle cell pain if any of these conditions apply.

So, for most patients with sickle cell, addiction is not a real worry and opiates remain a very useful pain killer for severe crises, despite their well known side effects. Special problems do arise however with the small number of sickle cell patients who have chronic pain, that is to say pain which is present almost every day. This is not the typical pattern in sickle cell, were recurrent acute crises are interspersed with pain free periods and, in the main, the reasons why some patients develop chronic pain are unknown. The temptation in this situation is to manage the chronic pain in the same way that we manage acute pain, by using opiate drugs. The conference at the Royal Society of Medicine made it clear that generally speaking opiates should not be used for chronic pain, whatever it’s cause.

The reasons for this are twofold: (1) Only a very small number of patients with chronic pain will respond to opiates and there is no way of predicting who they will be. Put another way, for most patients with chronic pain opiates are totally ineffective. (2) If opiates are used in a chronic pain situation the risks of addiction are very great. The burden for the patient is therefore made worse, by adding the problems of addiction to their existing chronic pain issues. For these two reasons, the general view of the conference was that opiates should be avoided in chronic pain and alternative ways of managing the pain must be considered. Not surprisingly, emotional and psychological distress are universal in patients with chronic pain and it is just as, if not more, important to treat these aspects as to treat the pain itself. The management of any patient with chronic pain must involve many other treatment modalities apart from drugs.

All this poses major problems for the small number of patients with sickle cell who have chronic pain. They are often treated on a long term basis with high doses of opiates, because these are the pain killing drugs which they and their doctors are used to using. Not only are the opiates almost certainly ineffective in this situation and they are at grave risk of addiction, but it is unrealistic to expect to be able to stop the opiates completely because they may always be required to manage an acute crisis. Doctors and patients have struggled with this problem for many years and there is no easy solution. Avoiding opiates in chronic pain situations is the ideal, but if they have to be used doctors and patients must use them responsibly to minimise the risks involved. This often involves detailed, repeated discussions between doctor and patient about the best way forward, as well as utilising many different modalities for pain management, including psychological interventions.

Tolerance and dependency are usually quite easy subjects to bring up with your doctors or nurses but discussing addiction is much more difficult because of the stigma attached to the word. If you think that you might have an addiction problem, it is very important to talk about this, it is much easier to get the help and support you need when the problem is discussed openly and honestly. Always remember – the benefits of morphine and the other opiate drugs are very great but they must be used wisely.


About rogerjamos

I am a consultant haematologist who has worked in Hackney, London, UK with patients who have sickle cell disease for many years. Knowledge is power; the hope is that this blog will empower patients by putting them in touch with contemporary research into sickle cell disease and facilitating informed discussion on the issues raised. Dr Roger Amos MA, MD, FRCPath
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