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Pain and opioids 

Pain and opioids
Chapter:
Pain and opioids
DOI:
10.1093/med/9780198714750.003.0012
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date: 14 November 2019

Introduction

Key concepts

Opioid dependence can be a difficult concept to grasp and to identify clinically in the setting of pain, particularly chronic pain. It is defined in ICD 10 as ‘a strong desire to take the drug, impaired control over its use, persistent use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes physical withdrawal reactions when drug use is discontinued’.

When there is chronic pain treated with long-term opioids, the clinician may be uncertain as to whether to attribute a patient’s preoccupation with opioid use to the increasing doses being taken, and deteriorating function, to their underlying pain, or to the development of opioid dependence (Box 12.1).

Alan Leshner, former Director of the US National Institute on Drug Abuse commented: ‘Addiction is not taking lots of drugs; it’s taking drugs and acting like an addict.’ This applies equally to the diagnosis of opioid dependence (addiction) in chronic pain. In DSM-5 the term ‘substance dependence’ has been replaced by ‘substance use disorder’ in part to avoid possible under-treatment of pain due to fear of addiction.

A cardinal feature of the dependence syndrome is the propensity to relapse—to return rapidly to compulsive drug use. Even after many years of drug abstinence, neuroplastic brain changes following drug dependence are not fully reversible, which explains the ongoing risk of relapse in patients with a history of opioid dependence. The risk of precipitating relapse is a concern in managing pain in such patients. It is critically important to re-double efforts of ‘recovery’ during periods when the use of an opioid is unavoidable for medical reasons.

Opioids in pain management

Opioids are uniquely effective in alleviating the affective component of pain—relieving anxiety and fear—as well as easing pain. However, when used in chronic pain, opioids have limitations, and several observational studies suggest poor functional outcomes in people treated with opioids. Side effects are not rare, and include nausea and vomiting, constipation, increased sweating, and decreased sexual function. In addition, opioid use can cause a syndrome of decreased pain tolerance, increased anxiety, depression, and sleep disturbances. Three factors contribute to this: opioid-induced hyperalgesia, withdrawal, and dependence/addiction.

Hyperalgesia

Opioid-induced hyperalgesia results from activation of specific brain and spinal cord pathways, with increased release of excitatory neurotransmitters and more intensive spinal synaptic transmission. All opioids, including methadone and buprenorphine, lead to a dose-dependent reduction of the pain threshold. Hyperalgesia is reversible with dose reduction or cessation of opioids.

Withdrawal

Withdrawal from opioids includes, among other features, generalized aches and pains, dysphoric mood, disturbed sleep, and craving for opioids. The emergence of withdrawal symptoms between doses causes increased pain (‘operant pain’) and contributes to a cycle of pain and drug use. This is particularly the case in patients using short-acting opioids. Regular use of long-acting opioids involves less reinforcement and less risk of operant pain than ‘as required’ usage of short-acting opioids.

Dependence/addiction

It is not known how often a patient with chronic pain, and no prior history of addiction, becomes addicted (e.g. displaying drug-seeking behaviours) as a result of being prescribed opioids. US reports of the risk of addiction in people receiving opioids vary widely, from 2% to 50%, and a recent review estimated 35% of people treated with opioids for chronic pain met criteria for a substance use disorder. However, this reflects in part the fact that many people using prescribed opioids have deliberately sought them, and often their addiction did not arise as a result of being prescribed opioids. If opioids are prescribed to patients with no addiction history, drug-seeking and related behaviours are relatively uncommon, but if prescribed to unselected patients, such behaviours are frequently seen.

Balancing benefit and risk

There is good evidence that opioids are effective for pain relief when used appropriately and in the short term, perhaps up to 3 or 4 months. Beyond that, the benefit/risk ratio begins to shift toward loss of efficacy and increased adverse effects, especially as measured functionally. The longer the opioid use and the higher the dose, the worse the picture becomes, although there will always be some patients who benefit from long-term stable use of opioids for pain and suffering.

The threshold seems to be around 100–120 mg equivalent dose of morphine per day and treatment duration of about 120 days. Certain patients are especially prone to developing problems with prescription opioids. Unfortunately, there is considerable evidence that the majority of prescribed opioids are prescribed precisely to the group of patients who are most likely to have problems with them, the so-called ‘adverse selection phenomenon’.

Influences on medical practice

The recent history of the use of opioids for treatment of non-malignant pain can be likened to the 40-year journey in the wilderness! Cicely Saunders’ founding of St Christopher's Hospice in the UK in 1967 highlighted the under-treatment of pain and the under-utilization of opioids for relief of pain and suffering. Emphasis on pain relief then began to overshadow the undoubted problems of loss of efficacy over time and the development of opioid dependence/addiction. The WHO issued guidelines for cancer pain relief in 1986 and the 2010 Declaration of Montreal by the International Association for the Study of Pain highlighted the under-treatment of pain.

The medical community began to advocate for pain relief to be regarded as a basic right of patients, and medicolegal cases found in favour of patients whose pain was inadequately treated. Yet concern about inappropriate use persisted. A pharmaceutical company was fined $635 million for claiming OxyContin® was less addictive than other opioid analgesics. The controversy continues, and some medical practitioners continue to prescribe large amounts of opioids for pain treatment while at the same time others face prosecution for over-prescribing opioids.

Epidemiology

Since the early 2000s there has been a steady increase in prescribing of pharmaceutical opioids globally, and also increases in morbidity and mortality related to these drugs. This has affected some countries to the extent there is talk of an epidemic of prescription opioid dependence and misuse. For example, in the US, 2 million Americans are estimated to be dependent on pharmaceutical opioids. Increasing fatal overdoses and dependence arising from use of prescribed opioid analgesics has also been reported in Canada, Europe, Asia, and Australia. The epidemic has been the result of increasing global prescription of opioids, driven by pharmaceutical industry marketing rather than clear evidence of long-term efficacy of opioids in chronic pain. Increased global prescribing has increased the availability of drugs, and the prevalence of prescription drug misuse.

Diversion

There is a latent demand for reinforcing drugs, and there is potential profit to be made throughout the supply chain—from manufacturing and marketing, prescribing, and diverting opioid drugs to the black market. Because potent opioids are tightly regulated, diversion often involves other medications, particularly oxycodone, as these drugs are often subject to lower levels of control. Diversion from opioid substitution treatment (OST) outlets contributes to the total amount of opioids available for purchase in the community.

Factors influencing the likelihood of prescribed opioids being diverted include:

  • formulation: e.g. high volume, dilute liquid is less easily diverted than tablets

  • availability: diversion of methadone from OST rises in proportion to the amount of unsupervised administration

  • availability of heroin: in settings where heroin is plentiful, there tends to be less diversion of prescription opioids

  • availability of treatment places: shortage of treatment places increases risk of diversion.

Assessing opioid addiction in patients with pain

The central features of the opioid dependence syndrome are often difficult to identify in patients with pain, especially chronic pain. Features such as (1) a strong desire to take the drug, (2) impaired control over use, (3) persistent use despite harmful consequences, (4) higher priority given to drug use than to other activities and obligations, (5) increased tolerance, and (6) sometimes physical withdrawal reactions may be denied, understated or explained away when the patient’s source of opioids is the medical practitioner. (See Box 12.2.)

Some of these behaviours, such as injecting oral medication, indicate a more serious problem than other behaviours such as using up a prescription early. It appears that the number of these behaviours in a patient is an indicator of the severity of dependence. Box 12.3 shows some predictors of misuse.

Managing pain, managing risk

Example

A patient with chronic low back pain (three surgical interventions) has been requesting progressively more analgesia, and has reached 760 mg oxycodone daily. The patient says the pain is bad and only oxycodone works. The GP is concerned, the pain specialist is concerned, and the GP notes that the patient has become increasingly estranged from his family.

Comment

In this situation, we have limited information. This is the reality of managing chronic pain—we are usually only aware of what the patient presents to us, and know little of what is going on. From this vignette, we know that:

  • the patient is taking high doses of an opioid (equivalent to approximately 2 g oral morphine daily), meaning the patient is highly tolerant and unlikely to be receiving optimal analgesia

  • there is poor functioning, reflected in family estrangement and doctors’ concern.

There is little doubt that the patient experiences back pain, but also little doubt that the primary problem is now opioid dependence. Non-pharmacological management is to discuss the diagnosis of dependence, set realistic objectives of treatment, and explain the rationale for switching to a long-acting opioid. Pharmacological management is to switch from oxycodone to methadone, initially with supervised dosing and slow dose increments to ensure safety during induction (the patient may not have been taking all his prescribed medication) and monitor compliance.

Principles of opioid prescribing

  • Single prescriber

  • Single pharmacy

  • Patient and prescriber sign opioid agreement

  • Lowest possible effective dose should be used

  • Do not combine opioids with sedative-hypnotics or benzodiazepines unless specifically indicated, and then with increased monitoring

  • Routinely assess functional and pain status

  • Monitor for medication misuse and compliance (urine drug screening).

The American Pain Society suggests doses of up to 200 mg morphine equivalent per day may be prescribed by generalist physicians. Above this level, referral for specialist assessment should be sought. The British Pain Society Guidelines recommend specialist referral for doses of 120–180 mg or greater (see Table 12.1 for dosage equivalence).

Table 12.1 Approximate equianalgesic doses of various opioids

Opioid

Oral

Parenteral

Duration of action (hours)

Morphine

30 mg

10 mg

Injection: 2–3 h

Codeine

180–200 mg

Linctus: 3–4 h

Methadone

  • Acute dosing 30 mg

  • Chronic dosing 7 mg (methadone accumulates—it takes 75 half-lives, or 5–7 days, to reach steady state levels)

In patients on methadone maintenance treatment, give two-thirds of the usual dose in two split doses IM

Syrup/tablet or injection: 6–8 h initially; increases to >24 hours with long-term use

Buprenorphine

0.4 mg

0.1 mg IV or SC

6–8 h

Oxycodone

10 mg

5 mg

  • 3–4 h tabs/injection

  • 12 h SR tab

Pethidine

100 mg IM or IV

2–3 h

Tramadol

100–150 mg

50–100 mg IM or IV

3–6 h

Fentanyl

100 micrograms IM, IV, SC

  • 0.5–2 h lozenge/injection

  • 72 h patch

Urine drug screening identifies inappropriate opioid and other drug use in patients with pain more frequently than does clinical assessment.

Management of chronic pain and opioid dependence

Chronic pain is common in people currently or previously addicted, and management of pain in these individuals is of critical importance. Under-treatment of pain and careless prescribing can both precipitate relapse to addiction in abstinent addicts, and can destabilize patients on OST.

Chronic pain management in current or former addicts

The limited efficacy of opioids for chronic pain, and risk of relapse on exposure to opioids, mean that in people who identify as abstinent former opioid addicts, and who are concerned at the risk of re-addiction, it is preferable to avoid opioid analgesics for management of chronic pain.

Former addicts who request opioid analgesics for chronic pain need a careful assessment of their pain, their addiction history and status, and their psychological functioning. If the pain appears something that is likely to respond to opioids, it is prudent that an addiction specialist assesses the patient prior to initiation of long-term opioid therapy. In some cases, the person seeking prescribed opioids may be intending to use the medication for their own purposes, but not necessarily as prescribed. Prescribed drugs are sometimes obtained for intoxication, to avoid withdrawal, or, in places where maintenance treatment with methadone is inaccessible, as an alternative maintenance medication. Even where treatment is accessible, some patients are deterred by the stigma, the loss of privacy, or the rigid rules which may be experienced in treatment programmes, and seek long-term prescriptions on the grounds of pain rather than enrolling in a treatment programme.

Managing pain, managing addiction

Data from clinical trials suggests only modest benefits of opioids over placebo in the management of chronic pain, but there is a substantial evidence base for the effectiveness of highly structured opioid prescribing in managing opioid dependence. Attempting to wean people with established opioid dependence and chronic pain from opioids can be difficult, and continuing long-acting opioids with appropriate safeguards and monitoring is often a pragmatic strategy. It is often unclear whether the primary diagnosis is pain or opioid dependence. Given the lack of certainty in identifying individuals at risk, some authors have recommended ‘universal precautions’—using the risk-management strategies applied in addiction treatment (including random urine drug testing) as the default assumption in prescribing opioids long term.

Effective prescribing for pain or addiction requires a clear diagnosis, rationale for treatment, objectives against which to assess effectiveness, monitoring with urine drug screens, and regular review. For people with a sense of loss of control over their pain, or over their drug use, externally imposed structure can be therapeutically useful, and direct observation of administration can be helpful at times.

However, there are also differences in treating pain and addiction. Methadone and buprenorphine, administered once daily in a stable dose, can suppress withdrawal for 24 hours, but do not provide 24-hour analgesia. They are more effective as analgesics if the dose is divided and given at intervals through the day.

High doses of methadone (>60 mg/day) are optimal in treating addiction, where the aim is to induce a high level of opioid tolerance, attenuating the effect of injecting heroin. However, in managing pain, lower doses, and less tolerance, are the preferred strategy.

Acute pain management in current or former addicts

Management of addicted individuals can be difficult as addicted patients are not always open about their addiction. They may be using multiple drugs. Even if they report using heroin, their actual level of tolerance cannot be accurately determined by history, as street drugs are of variable purity. While hospitalized, some addicted individuals may self-medicate, placing themselves at risk of toxicity, drug interactions, and complications of injecting.

  • Opioids are not contraindicated in abstinent, former addicts with acute pain. There is a poorly defined, probably small risk that exposure to opioids will trigger relapse to addiction. If possible, this risk should be discussed with the patient who may prefer non-opioid analgesia.

  • If opioids are used for pain management in recovering addicts, medication should be transferred to long-acting opioids at the earliest opportunity. Support should be offered during hospitalization, and follow-up arrangements put in place. Such structure helps protect patients against the risk of relapse.

  • In patients on OST with acute pain, withdrawal needs to be controlled and analgesia given in addition; this means continuing OST in hospitalized patients and giving additional opioid analgesia as needed. People on buprenorphine undergoing elective surgery should continue their usual dose, and have additional opioid analgesia titrated against response; some may require additional modalities of pain relief.

  • In hospitalized heroin users, prescribing methadone can prevent opioid withdrawal complicating management. When initiating methadone in hospitalized patients, or continuing methadone in people whose medication has not been supervised, titrating regular small doses (10–20mg) against response is required. Induction onto methadone is complex due to variable pharmacokinetics. In people who metabolize the drug slowly, methadone accumulates over several days, and a dose which might have been safe on day 1 can be toxic on day 2 or 3. Patients need to be monitored for signs of toxicity during the first week of methadone.

  • A non- judgemental stance is necessary for effective assessment and management, which is optimized by access to skilled and experienced addictions staff.

  • If prescribing opioid analgesics to abstinent ex-addicts switch from short- to long-acting medications as quickly as appropriate (to minimize reinforcing effects). They may also benefit from additional support during postoperative periods.

Issues in service delivery

Competencies

  • Prescribing for chronic pain requires competence, comprising knowledge, skills, and attitudes. Maintenance of competence requires the opportunity to reflect on practice.

  • Knowledge includes opioid pharmacology, and principles of managing pain and of managing addiction. Good communication skills are critical in managing pain and associated anxiety, and an empathic, non-judgemental stance is needed in relating to all patients. Clinicians need to be able to recognize and diagnose opioid dependence, to be able to set realistic objectives of treatment, and to monitor and adjust treatment according to response.

  • Standardized tools (such as screening questionnaires) have serious limitations, and are not a substitute for competent assessment. The decision of how to manage, and whether to prescribe opioids, needs to be reached in agreement between an appropriately skilled doctor and patient.

Treatment systems

  • Effective pain management in complex patients is the result of the interaction between the clinician’s competence, and the setting in which he or she works. A competent practitioner working in a chaotic system in which information is not shared can have difficulties achieving safe and effective pain management. A hospital with comprehensive policies and procedures cannot guarantee good care of patients if individual practitioners are not supported in dealing with complex, stigmatized patients.

  • Opioid dependence is sufficiently common that all hospitals should have protocols for the management of pain in people identified as opioid dependent. These protocols should deal with history taking, identification and management of withdrawal, continuation of OST in hospitalized addicts, and provision of pain relief in people with current or past addiction. Such protocols are more likely to be useful if supported by training. Ideally, large hospitals should have an addictions consultation-liaison service, to provide training, assess and advise on management of complex patients, and support staff in management. Pain management is likely to be more effective if an acute pain team is available to provide support in complex cases.

  • Addiction services need skilled staff familiar with the principles of chronic pain management, able to assess and refer patients appropriately.

  • Given the overlap between chronic pain and opioid dependence, pain clinics should not only liaise with addiction services regarding individual patients, but should have access to specialist addiction assessment.

Further reading

Australian and New Zealand College Anaesthetists and Faculty of Pain Medicine (2010). Acute Pain Management: Scientific Evidence (3rd ed). Melbourne: ANZCA and FPM.Find this resource:

Chou R, Fanciullo G, Fine PG, et al. (2009). Opioids for chronic noncancer pain: Prediction and identification of aberrant drug-related behaviors: A review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain 10:131–46.Find this resource:

Substance Abuse and Mental Health Services Administration (2012). A Treatment Improvement Protocol. TIP 54 Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders. Rockville, MD: SAMHSA.Find this resource: