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

Imagine experiencing a burning, tingling sensation, and numbness in your legs every day that gets worse over time – and your doctors can't find a reason for it.

This is the situation for millions of people with 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 nerve disease. So this is a condition of unknown cause that damages several nerves. The nerves most affected are usually those that sensitize the legs and feet.

Other terms are sometimes used, including cryptogenic neuropathy or chronic polyneuropathy of undetermined cause. In some people, neuropathy is due to diabetes, alcohol abuse, medication, or other medical conditions. In almost half of all cases, however, sensory polyneuropathy is idiopathic.

No cause, no cure

Whichever name is used, the condition is frustrating, annoying, and sometimes debilitating. And without a recognizable and reversible cause, there is no cure. Although a number of drugs are commonly prescribed, it is not clear which one is the most effective or the safest. Therefore, doctors generally recommend a trial and error phase. Drugs are prescribed one at a time until they are determined to be effective and not causing any intolerable side effects.

Unfortunately, it can take many months or even longer to find an effective treatment. Doctors have little guidance in knowing which to start with. This is why research comparing treatment options is so important – and yet little comparative research has been published on treatments for idiopathic sensory polyneuropathy.

The researchers compare four treatments for neuropathy

Researchers who publish in JAMA Neurology describe the results of a unique study 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 reported whether they stopped taking the drug because of side effects, expense, or other reasons.

While the attempt is important and much needed, the results have been disappointing.

No drug was a clear winner or highly effective. For this study, a key measure was whether a drug reduced symptoms by 50%. The most effective treatment was nortriptyline. Of the subjects who took this drug, 25% said their symptoms improved by at least 50%. The least effective treatment was pregabalin: only 15% of the subjects reported a large improvement.
Side effects were common with all treatments. Nortriptyline had the highest rate of side effects at 56%. Mexiletine had the fewest at 39%. Fortunately, none of the side effects were considered serious.
People often stop taking their assigned medication. Duloxetine had the fewest withdrawals (37%). The highest dropout rate was for mexiletine (58%). Reasons for stopping were side effects and costs.

The study wasn't perfect

This attempt had a number of important limitations:

The process only took 12 weeks. For a condition that is usually lifelong, longer term results would be more helpful.
The four drugs compared in this study were chosen because they work in different ways. However, it did not include other commonly prescribed drugs. For example, this study doesn't say anything about how well gabapentin, amitriptyline, or carbamazepine would have worked.
The subjects could be treated with a drug that they had been taking before the experiment, even if it hadn't worked for them.
The dropout rate included factors unrelated to how safe or effective the drug was. Drug costs were particularly important in this regard.
Most of the subjects (85%) were white. The results could have been different if a more diverse study population had been enrolled.

The final result

Direct comparisons of treatments for idiopathic sensory polyneuropathy – what many refer to simply as neuropathy – are urgently needed, so this study is important. However, the biggest takeaway message from this research is that many topical treatments are not very good.

Overall, nortriptyline and duloxetine appeared to outperform the other drugs in this study, so they would be good choices at first instead of pregabalin and mexiletine. However, when the best treatments only work well for a quarter or less of patients, and almost half treatment is stopped in the first 12 weeks, it is clear that better, safer, and cheaper treatments are needed.

We may already have better treatments that weren't part of this study. We need additional comparative research to know for sure.

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