Augmentation in restless leg syndrome can be difficult to manage and actually occurs relatively commonly. In fact, some studies suggest that most people taking dopamine agonists for restless legs will develop augmentation over time. In 2016, guidelines were published which provide a useful guide to managing augmentation when it develops.

What is augmentation?

Augmentation is when people who are on long term treatment with dopaminergic agonists for restless legs develop a worsening in their restless leg symptoms over time. It was first described in 1996 and at that point was felt that about 75 percent of people on levodopa or other short term dopamine agonists would go on to develop augmentation.

In the year since when it has been more systematically studied, it appears that around eight percent of people on long term dopamine agonists develop augmentation each year they are on treatment.

The common symptoms that people describe, which actually characterise augmentation is not just a worsening or greater intensity of symptoms. It’s finding that symptoms occur earlier in the day, which can be two to four hours earlier than they were previously coming on. It can take less time for symptoms to come on after sitting down or beginning to rest. Symptoms occur in other parts of the body, so spread up the legs, into the arms, into the trunk and drugs seem to have a shorter duration of effect and aren’t as effective for as long a period.

Based on that, the International Restless Leg Syndrome Study Group developed four questions that can be used clinically to screen for augmentation:

  1. Do the symptoms appear earlier than when the drug was first started?
  2. Are higher doses of the drug now needed, or do you need to take the medicine earlier?
  3. Has the intensity of symptoms worsened since starting the medication?
  4. Have symptoms spread to other parts of the body (eg arms) since starting the medication?”

How should augmentation be managed?

The most effective strategy for managing augmentation is to prevent it occurring in the first place, by not using dopamine agonists. This is reflected in the change in treatment guidelines, with dopamine agonists no longer being first-line therapy for restless legs syndrome. It’s also important to look at non-drug strategies in managing restless leg symptoms before using any prescription medication: making sure iron stores are adequate, looking at strategies such as massage, pacing or movement as a way of managing people’s symptoms. If people do need a medication, first-line therapy should be an alpha-2-delta ligand, such as gabapentin, pregabalin. If people do need a dopamine agonist, because they don’t respond to other medications such as alpha-2-delta ligands, the dopaminergic load should be kept low by using the minimum effective dose for the shortest required period of time.

Reduce exacerbating factors:

  • Measure serum ferritin and if <75mcg/ml or transferrin saturation <20% consider iron replacement. Whilst this could be with oral iron, this is often poorly tolerated, so intravenous (IV) iron can be considered.
  • Review lifestyle factors that may be exacerbating restless legs such as caffeine or alcohol, sleep deprivation or stress.
  • Consider whether other medications people are taking may be contributing such as anti-depressants or other medications with anti-cholinergic effects such as anti-histamines.

Review dopaminergic therapy:

  • In mild augmentation, current dopamine agonists could be continued, advancing the time of the dose to before symptom onset, or adding an earlier dose in addition to the current night-time dose. If symptoms are occurring predominantly at night, the night-time dose could be increased. Alternatively the dopamine agonist could be switched to an alpha-2-delta ligand such as gabapentin or pregabalin, or a longer acting dopamine agonist such as rotigotine.
  • In more severe augmentation, the dopamine agonist should be reduced or stopped if possible. This can be done by substituting with an alpha-2-delta ligand or changing to rotigotine. Once these have started then the shorter acting dopamine agonist (eg pramipexole or ropinerole) can be gradually reduced. It is important to warn people that with reducing short acting dopamine agonists there is often a withdrawal effect and restless legs symptoms can temporarily worsen. A 10 day washout period once dopamine drugs are weaned, where people are on no medication can be considered to evaluate symptoms and determine whether ongoing medications are needed. However, this often leads to very severe restless legs symptoms and profound insomnia that may last 4 or 5 days or longer. If augmentation is severe and symptoms are occurring almost 24 hours a day, a low dose opiate could be considered.

What do I do?

If someone has already got augmentation, my approach is generally to ensure that their iron stores are adequate. Sometimes augmentation can develop in people who are actually stable on dopamine agonists but get low iron stores which exacerbates their restless leg symptoms.

If augmentation is relatively mild, I won’t necessarily switch people off dopamine agonists. I might even temporarily increase the dose, really to get a sense if they’re beginning to develop augmentation,  knowing I’m going to have to switch them off the drug at some point. But if they are not doing too badly, temporarily increasing the dose buys more time before they have to switch off the drug. Another thing I will try is splitting the dose of the dopamine agonist, so that they’re a lower dose at two time points or getting them to take the dopamine agonist a little earlier.

If people don’t respond to that strategy or have got more severe symptoms, they do need to switch from the dopamine agonist to something else. The aim is to really get people off dopamine agonists but it’s not always possible. So they will end up reducing the dose of dopamine agonists, if I can’t switch them completely to something else and will sometimes actually switch to a different dopamine agonist. The only one I switch to is rotigotine because of its longer duration of action and therefore reduced propensity, or at least thought reduced propensity, for developing augmentation.

This is also a group where I will consider a high potency opioid as a bridge so that people might be on an opioid for a couple of months while they’re getting off the dopamine agonist, letting things settle and eventually rotating back to going on to a lower dose of dopamine agonist again.

Just because someone develops augmentation doesn’t mean they can’t ever go back onto dopamine agonists and often it’s a case of just giving them a break from the dopamine agonist for a period of time as they try for a couple of months. Then they find they can get back to the dopamine agonist and again be successfully treated for a period of time.

What should you do if you think you have developed augmentation?

If you think you have or are developing augmentation of your restless legs symptoms, you should contact your treating doctor so they can review your clinical symptoms and medication and make a plan to manage your symptoms.

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