Methadone for neuropathic pain in adults

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Bottom line
There is no good evidence to support or reject the suggestion that methadone works in any neuropathic pain condition.

Neuropathic pain is pain coming from a damaged nervous system. It is different from pain messages that are carried along healthy nerves from damaged tissue (e.g. from a fall or cut, or an arthritic knee). Neuropathic pain is often treated by different medicines (drugs) from those used for pain from damaged tissue, which we often think of as painkillers. There are different types of neuropathic pain, with different causes. Some medicines that are used to treat depression or epilepsy can be very effective in some people with neuropathic pain by altering the signal that is carried along nerves that transmit painful stimuli (something that results in a change in how the body works). Sometimes opioid painkillers are used to treat neuropathic pain. Opioid painkillers are drugs such as morphine. Morphine is derived from plants, but many opioids are also made by chemical synthesis rather than being extracted from plants. Methadone is one of these synthetic opioids. Methadone has many characteristics that make it different from other opioids, which may influence its effectiveness or the side effects that patients experience.

Study characteristics
In November 2016, we searched for clinical trials where methadone was used to treat neuropathic pain in adults. We found three small studies, enrolling 105 participants, that met our requirements for the review. The studies were all quite different in their design: the methods of two studies reflected how frequently methadone is prescribed in practice, in that participants received it twice or three times daily. One trial had a more experimental design. All three trials had two phases. The lengths of the studies varied, from 20 days to around eight weeks for each phase. The studies were similar in that all administered low doses of methadone, which may or may not reflect the doses typically prescribed in clinical practice.

Key findings
Two studies looked at how many participants got at least 30% pain relief. Eleven of 29 participants receiving methadone achieved 30% pain relief versus seven of 29 receiving placebo. In one study, none of the 19 participants achieved a 50% reduction in pain intensity, either when receiving methadone or when receiving placebo (a sugar pill). These reductions in pain intensity have been shown to be important to patients. In addition, one study found improvements in average and maximum pain intensity and pain relief when comparing methadone with placebo.

In the two studies that reported dropouts from the study, none of 29 participants dropped out because they thought methadone or the placebo was not helping their pain; whereas four of 29 dropped out because of side effects while taking methadone and three of 29 while taking placebo.

One study reported how many participants had specific side effects, and found increased dizziness with methadone compared to placebo. There were no serious side effects or deaths reported. There was so little information from these studies that we concluded there was no convincing evidence to support or reject a meaningful benefit for methadone versus placebo or any other treatment.

Quality of the evidence
We rated the quality of the evidence as very low because there were only three small studies with different designs, and with few participants and events. In addition, the studies were probably not long enough to show how well methadone would work (or how safe it would be) over a longer time period. Very low quality evidence means that we are very uncertain about the results.