Morphine effective for cancer [and other] pain

Oral morphine effective for cancer pain –  April 2016 – Cochrane review

Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain.

Morphine taken by mouth produced good pain relief for most people with moderate or severe cancer pain.

The only difference between cancer and non-cancer pain is political and moral, not medical (see no difference between cancer pain and non-cancer pain, so this really means morphine is effective for many kinds of pain. (I’m sure soldiers wounded on the battlefield would agree.)

One person in two or three who gets cancer will suffer from pain that becomes moderate or severe in intensity. The pain tends to get worse as the cancer progresses.

Morphine taken by mouth has been used since the 1950s for controlling cancer pain. In 1986 the World Health Organization recommended taking an oral solution of morphine every four hours.

Morphine is now available in a number of different formats that release the morphine over various periods of time. Morphine immediate release is rapidly absorbed, and would usually be taken every four hours.

Modified release tablets are available that release morphine more slowly, so that they can be taken only twice a day or even only once a day.

Study characteristics

In this updated review we set out to estimate how well morphine worked, how many people had side effects, and how severe those side effects were

We found 62 studies with 4241 participants. The studies were often small, compared many different preparations, and used different study designs.

This made it difficult to work out whether any one tablet or preparation of oral morphine was better than any other. There did not seem to be much difference between them.

Key findings

  • More than 9 in 10 participants had pain that went from moderate or severe before taking morphine to pain that was no worse than mild when taking morphine.
  • More than 6 in 10 participants were very satisfied with the morphine treatment, or considered the result to be very good or excellent.
  • Only about 1 person in 20 stopped taking morphine because of side effects. Morphine is associated with some unwanted effects, mainly constipation, and nausea and vomiting.

Quality of the evidence

At one level these are good results. On another level, the quality of studies is generally poor and we could wish for more consistency in study design, and especially in study reporting, which should include the outcome of pain reduced to tolerable levels – no worse than mild pain – so that people with cancer are not bothered by pain.

But it’s ok for everyone else to be “bothered by pain”?

Authors’ conclusions:

The effectiveness of oral morphine has stood the test of time, but the randomised trial literature for morphine is small given the importance of this medicine.

That’s because all the latest studies are only counting opioid milligrams without any relationship to pain levels.

Only a few reported how many people had good pain relief, but where it was reported, over 90% had no worse than mild pain within a reasonably short time period

Lately, the amount of pain study subjects are suffering from and how much of it is relieved seems to be considered inconsequential.

Pain levels are not measured at all while dependence is considered the main outcome, despite it being an entirely expected and unremarkable side effect of many medications.

The review demonstrates the wide dose range of morphine used in studies, and that a small percentage of participants are unable to tolerate oral morphine.

The “wide dose range” even among opioid-naive cancer patients makes any standardized doses, as recommended by the CDC, medically invalid.

Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in cross-over design studies.

It was not clear if these trials were sufficiently powered to detect any clinical differences between formulations or comparator drugs.

New studies added to the review for the previous update reinforced the view that it is possible to use modified release morphine to titrate to analgesic effect.

There is qualitative evidence that oral morphine has much the same efficacy as other available opioids.

That’s because “other available opioids” (at least by prescription, not heroin or illicit fentanyl) are all based on morphine.

Other thoughts?

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