Opioids for chronic pain: meta-analysis from 2006

Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects – 2006 May – free full-text PMC1459894

This meta-analysis was carried out with these objectives:

  1. to compare the efficacy of opioids for CNCP with other drugs and placebo;
  2. to identify types of CNCP that respond better to opioids; and
  3. to determine the most common side effects of opioids.  

We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo)

Extracted outcomes included pain, function or side effects.


Included were 41 randomized trials involving 6019 patients:

  • 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain);
  • 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain);
  • 7%, fibromyalgia; and
  • 1%, mixed pain.

The methodological quality of 87% of the studies was high.

The opioids studied were classified as

  1. weak (tramadol, propoxyphene, codeine) or
  2. strong (morphine, oxycodone).

Average duration of treatment was 5 (range 1– 16) weeks.

Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups.

  • Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia.
  • Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief.
  • Among the side effects of opioids, only constipation and nausea were clinically and statistically significant.


  • Weak and strong opioids outperformed placebo for pain and function in all types of CNCP.
  • Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids
  • Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.

Below is the Full Study Text

Opioids are the most potent analgesics available and are well established for the treatment of severe acute, surgical and cancer pain

However, their use to ameliorate CNCP is still controversial because of the side effects of opioids, the physical tolerance they build up (with the related withdrawal reactions and possibility of addiction) and anxiety over disapproval by regulatory bodies

Nowhere is it mentioned that their effectiveness is in doubt.

The objectives of this review were 4-fold:

  1. to determine the efficacy of opioids for CNCP compared with placebo;
  2. to compare the effectiveness of opioids for CNCP with that of other drugs;
  3. to identify categories of CNCP with better response to opioids; and
  4. to determine the most common side effects and complications of opioid therapy for CNCP, including incidences of opioid addiction and sexual dysfunction.

The full article goes into great detail of what the studies showed.


This systematic review demonstrated that, based on the available trials analyzed:

  • Opioids were effective in the treatment of CNCP overall; they reduced pain and improved functional outcomes better than placebo.
  • Tramadol reduced pain and improved functional outcomes in patients with fibromyalgia.
  • Strong opioids (oxycodone and morphine) were significantly superior, statistically, to naproxen and nortriptyline (respectively) for pain relief but not for functional outcomes.
  • Weak opioids (propoxyphene, tramadol and codeine) did not significantly outperform NSAIDs or TCAs for either pain relief or functional outcomes.
  • Clinically (> 10%) and statistically, only constipation and nausea were significantly more common with opioids.

Although recent studies have indicated that endocrinological abnormalities and erectile dysfunction can be experienced by patients taking opioid medication for chronic conditions, most researchers did not ask participants about sexual dysfunction.

The few studies in our review that collected such data were relatively short for the observation of any endocrinological abnormalities. The only 2 studies that reported data on sexual function showed that patients taking opioids actually perceived themselves as doing better in terms of sexual behaviour compared with those in the control groups. Improvement of well-being secondary to better pain control may account for this result

Addiction or opioid abuse in patients with chronic pain cannot be assumed not to exist (despite popular statements), because the existing randomized trials are not designed to evaluate it;

the duration of the trials was too short to allow for the development or detection of aberrant drug use, even if appropriate screening tools for addiction had been used.

This makes no sense since addiction is reported to be instantaneous when a person who has the disease of addiction first ingests an opioid.

An adequate measure of “diagnosis of addiction” is also lacking in every study. For example, it is hazardous to equate reported “drug craving” or “reported symptoms and signs of addiction” with addiction.

Furthermore, none of the studies have been methodologically sound enough to allow for conclusions about opioid addiction or abuse.

The results of our review were similar to those of others recently conducted.

In 2004, Kalso and colleague systematically reviewed studies of World Health Organization step 3 opioids for CNCP and found the mean decrease with opioids in pain intensity in most studies to be at least 30%, with comparable effects on neuropathic and musculoskeletal pain.

Eisenberg and coworkers’ 2005 systematic review of 8 randomized controlled trials of opioid agonists (excluding tramadol) for neuropathic pain demonstrated opioid efficacy for spontaneous neuropathic pain with intermediate-term follow-up.

Moore and McQuay recently published a systematic review of the side effects of opioids for chronic nonmalignant pain; they found the most common adverse effects to be dry mouth (25%), nausea (21%) and constipation (15%).


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