Adverse effects of long term opioid use


Evidence indicates that opioids are less effective for persistent pain than acute pain.
Opioids may provide up to 30% reduction in persistent pain and are only helpful for
opioid sensitive (nociceptive) pain and only some neuropathic pain states. None of
the studies reviewed for opioid use in chronic pain ever lasted more than 16 weeks.
There are no randomised controlled trials on the long term effectiveness of opioid use
in chronic non-cancer pain. In a systematic review of 111 trials with administration of
opioids either orally or topically, only 4 studies evaluated effectiveness beyond 6
months. One evaluated tapentadol with weak positive evidence, the second
evaluated morphine with negative evidence, the third evaluated oxycodone with
negative evidence, and the fourth evaluated fentanyl and morphine with indeterminate
results.¹ Many pain medicine specialists now recommend a maximum of 100 mg
Morphine for 90 days only.

The daily dose of opioid among patients receiving opioids for non-malignant pain is
strongly associated with opioid-related mortality. More than 100mg of oral morphine
per day results in a two fold increase in the risk of death, more than 200mg results in
three fold risk increase.² Avoid using opioids with other sedative medication including
benzodiazepines, alcohol, cannabis and antihistamines.

Oxycontin has the highest demand for diversion in Australia. Injecting drug users in
Australia indicate more than 1 in 6 had used pharmaceutical drugs illicitly (i.e. using
medications not prescribed for them).³ Safer medication for chronic pain may be
Norspan patches or Targin.

Opioids cause a decrease in various hormones including testosterone. This can
result in loss of libido, sexual dysfunction, infertility, muscle weakness, fluid retention,
osteoporosis and fractures.

Opioids contribute to depressed respiratory effort and exacerbation of sleep apnoea.
It is recommended that patients who require greater than 50mg methadone or 150mg
morphine equivalent per day should be referred for formal sleep apnoea
evaluation. It is also recommended to advise patients to decrease their daily opioid
doses by at least 30% during respiratory tract infection or asthmatic episodes for
safety reasons.4

There is a growing body of evidence that opioid use, especially longer term and
higher doses can make the pain experienced more severe. Weaning opioids may
lead to improved pain levels with less side effects.
Fact sheet Health Professional Information

Patients on long-term opioids therapy are often upset when they discover dental
caries and need for dentures were caused by opioid therapy.

Opioids increase risk for infection, and may contribute to malignancies.

Opioids cause cognitive slowing, adverse effect on mood, impaired concentration,
memory, driving ability and increased risk of falls. The SA Drugs of Dependence Unit
suggests formal driving test is needed for drivers using more than 200mg oral
morphine equivalent per day.
They also warn of risks mixing opioids and other
sedative drugs.

A side effect that does not resolve over time.

Many patients are reluctant to entertain the idea of weaning opioids simply because “I
never took them for a few days and then I really felt it”. This is a withdrawal reaction
and opioids can be weaned slowly and safely.

Chronic non-malignant pain and depression are closely linked with one-half to two
thirds of people being less able or unable to exercise, enjoy normal sleep, perform
household chores, attend social activities, drive a car, walk or have sexual
intercourse. The risk of death by suicide seems also to be doubled in chronic pain
patients compared with controls. The treatment of chronic pain patients should
therefore encompass a multi-disciplinary approach addressing co morbid mental
health issues and teaching non medication strategies for dealing with pain and the
principles of pacing. This would include referral to psychologists and
physiotherapists. Opioids in such a group of patients can be counterproductive.³
Therefore consider weaning opioids by a rate of 10% every 1-2 weeks to minimise
side effects if the patient has persisting pain despite being on opioids.

Individual drugs have specific risks e.g. Methadone can prolong QT syndrome and
patients on Methadone should have an ECG to exclude this.

Manchikanti et al. Focussed Review - Effectiveness of Long-Term Opioid
Therapy for Chronic Non-Cancer Pain. Pain Physician 2011;14:E133-E156
Gomes T et al. Less is More - Opioid Dose and Drug-Related Mortality in
Patients With Nonmalignant Pain. Arch Intern Med. 2011;171 (7):686-691.
Prescription Opioid Policy. A publication by The Royal Australian College of
Physicians, Faculty of Pain Medicine ANZCA, The Royal Australian College
of General Practitioners and The Royal Australian and New Zealand College
of Psychiatrists.
L Webster. President’s Message (American Academy of Pain Medicine) –
Eight Principals for Safer Opioid Prescribing. Pain Medicine 2013;14: 959-
DASSA Website. Benzodiazepines , opioids and driving.

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