Treating neuropathy: Which medication is best? – Harvard Health Blog

Imagine feeling burning, tingling, and numbness in your legs day in and day out, which gets worse over time – and your doctors can’t find a reason for it.

This is the situation of millions of people who suffer from idiopathic sensory polyneuropathy. The term “idiopathic” means that no cause can be identified; “Sensory” refers to the type of nerve, in this case, those that carry nerve signals such as pain or temperature; “Poly” means “many” and “neuropathy” means nervous disease. So, it is a condition of unknown cause which damages several nerves; the nerves most affected are usually those that provide sensation to the legs and feet.

Sometimes other terms are used, including cryptogenic neuropathy or chronic polyneuropathy of undetermined cause. For some people, neuropathy is due to diabetes, alcohol abuse, medication, or other conditions. But in nearly half of the cases, sensory polyneuropathy is idiopathic.

No cause, no cure

Regardless of the name used, the condition is frustrating, annoying, and at times debilitating. And without an identifiable and reversible cause, there is no cure. Although a number of drugs are commonly prescribed, it is not clear which is the most effective or the safest. So, doctors usually recommend a period of trial and error. One drug after another is prescribed, until a drug is found that is effective and does not cause intolerable side effects.

Unfortunately, it can take several months, or even longer, to find a treatment that works. Doctors have little advice on where to start. This is why research comparing treatment options is so important – and yet, little valuable comparative research on treatments for idiopathic sensory polyneuropathy has been published.

Researchers compare four treatments for neuropathy

Researchers publishing in JAMA Neurology describe the results of a single trial in which 402 people with idiopathic sensory polyneuropathy were randomly assigned to one of four drugs: duloxetine, mexiletine, nortriptyline, or pregabalin. After 12 weeks, each person rated their neuropathy symptoms on a scale of 1 to 10, noted side effects, and indicated whether they had stopped taking the drug due to side effects, cost, or some other reason.

Although the trial is important and necessary, the results have been disappointing.

  • No drug was clearly winning or very effective. For this study, a key measure was whether a drug reduced discomfort by 50%. The most effective treatment was nortriptyline. Of the study subjects taking this drug, 25% said their discomfort improved by at least 50%. The least effective treatment was pregabalin: only 15% of study subjects reported this improvement.
  • Side effects were common to all treatments. Nortriptyline had the highest rate of side effects at 56%. Mexiletine had the least with 39%. Fortunately, none of the side effects were considered serious.
  • People frequently stop taking the assigned medications. Duloxetine had the fewest stops (37%). The highest discontinuation rate was for mexiletine (58%). Reasons given for quitting include side effects and cost.

The study was not perfect

This trial had a number of important limitations:

  • The trial lasted only 12 weeks. For a condition that usually lasts a lifetime, longer term results would be more helpful.
  • The four drugs compared in this trial were chosen because they work in different ways. But other commonly prescribed drugs were not included. For example, this trial tells us nothing about the performance of gabapentin, amitriptyline, or carbamazepine.
  • Study subjects could be treated with any medication they had taken before the trial, even if it had not worked for them.
  • The discontinuation rate included factors unrelated to the safety or effectiveness of the drug. The cost of drugs was particularly important in this regard.
  • Most of the study subjects (85%) were white. The results could have been different if a more diverse study population had been recruited.

The bottom line

Direct comparisons of treatments for idiopathic sensory polyneuropathy – which many simply call neuropathy – are badly needed, so this trial is important. Yet the biggest takeaway message from this research is that many current treatments are not very good.

Overall, nortriptyline and duloxetine appeared to outperform the other drugs in this trial, so they would be good choices to start with rather than pregabalin and mexiletine. But when the best treatments work well for only a quarter or less of patients, and almost half drop out within the first 12 weeks, it’s clear that better, safer, and cheaper treatments are needed.

Maybe we already have better treatments that weren’t part of this trial. We will need further comparative research to find out for sure.

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Jothi Venkat

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