Mauro Manconi and Diego García-Borreguero (eds.)Restless Legs Syndrome/Willis Ekbom Disease10.1007/978-1-4939-6777-3_14

14. Management of Augmentation

Diego García-Borreguero¹

(1)

Sleep Research Institute, Madrid, Paseo de la Habana, 151, 28036 Madrid, Spain

Diego García-Borreguero

Keywords

Augmentation with dopaminergic drugsDopaminergic drugs and augmentationRestless legs syndrome and augmentationTramadol for restless legs syndromeLevodopa for restless legs syndrome

Augmentation is a major clinical problem that emerges with the long-term treatment of RLS/WED. It can produce a severe exacerbation of RLS/WED symptoms and is thus something to be carefully assessed and managed. Some degree of augmentation has been reported with the use of all investigated dopaminergic drugs [1–5], tramadol being the only exception among the non-dopaminergic substances [6]. In the virtual absence of direct comparative studies between dopaminergic agents, the incidence rate seems to be highest during treatment with levodopa and higher for shorter acting (pramipexole, ropinirole) than longer acting (rotigotine, cabergoline) dopamine-receptor agonists. However, it is unclear whether this finding is related to masking of earlier symptom onset by the longer acting dopaminergic agents, or whether this reflects a truly reduced risk of augmentation.

The propensity of augmentation increases with longer duration of treatment and possibly with higher doses. [7, 8] It is unclear whether the apparent relationship between dose and augmentation rate is, in fact, secondary to patient characteristics such as disease duration or severity. Nevertheless, it is recommended that dose increases be carefully considered, particularly if they exceed usually accepted or approved dose levels. Increases should be limited to breakthrough of clinically important symptoms that cannot be managed behaviorally [9] and should be balanced against the option of adding an alternative type of medication.

When to Treat Augmentation?

Augmentation can sometimes be mild and not interfere with the main activities of the patient. Thus, any decision on whether to treat augmentation is usually guided by the presence or absence of clinical relevance.

Among the criteria that might be helpful to define clinical relevant augmentation are [10]:

a.

Change in daily activities and/or behavior (e.g., the patient stops riding in cars in the afternoon) due to augmentation;
b.

Negative impact on the patient’s quality of life (sleep, mood, etc.) due to augmentation;
c.

Need to change the treatment dose or the patient needs to take the dose earlier in the day (e.g., dividing the dose);
d.

Adjustments in concomitant medication are made to compensate for augmented RLS symptoms (e.g., an increased intake of analgesics or hypnotics to cover an increase in symptom intensity);
e.

Any other aspect as judged by the evaluator.

Furthermore, in some cases, the only sign of augmentation might be a minimal reduction of the efficacy of the dopaminergic treatment. In this way, patients might notice only mild RLS/WED symptoms during the day that are not bothersome because usual daytime activities help to alleviate them. Although, in such cases no change of treatment might be necessary. Some preventive measures are always needed to avoid a progression of the condition: physicians and patients should be aware that dopaminergic medication might lead to an iatrogenic increase in symptom severity and should be encouraged to use lower dopaminergic doses. Moreover, a careful observation of the clinical course will be necessary in such cases to allow future changes in the severity of symptoms to be noticed.

Even in mild cases, before a change of treatment regimen is even considered, serum ferritin levels should be measured [7]. Thus, if serum ferritin is <75 µg/L, oral iron treatment should be considered [7]. Furthermore, any medication that might exacerbate RLS/WED symptom severity, such as antidepressants, antihistamines or dopamine blockers should be carefully reviewed and eventually interrupted.

When the sole sign of augmentation consists of symptoms starting earlier in the day, without an increase in the number of hours occupied by symptoms over the entire 24-hr period, the time of administration of the dopaminergic medication can be changed to an earlier time in the afternoon. However, if the earlier onset of symptoms in the day is accompanied by an increase in the number of hours with symptoms each day, dividing the tablet into two halves (with one half being administered earlier in the PM and a second one at bedtime) is a frequently used strategy. However, no empirical evidence exists on its efficacy to effectively alleviate symptoms or to prevent the on-going process of augmentation. A reasonable caution when doing this would be to ensure that the actual plasma levels obtained by partition of the former dose are still therapeutic. An alternative, but still relatively unexplored strategy based on the same concept would be the use of an extended release form of the same medication that had been used before [11].

Only gold members can continue reading. Log In or Register to continue