Treatment of RLS and PLMD in adults - Oct 2019 literature review

[YodaDog]

I came across this on the internet and found it very interesting:

uptodate.com/contents/treat...

[Hidden]

Good read, and in fact it should be a MUST read for any Dr who has a patient with RLS. It's a pity they didn't mention the fact that severe RLS can spread to the rest of the body (unless I missed it), but otherwise a sound bit of work.

Plus they didn't mention the ****ing soap!!!!

[YodaDog in reply to Hidden]

It's in there (albeit briefly) in the section on augmentation.

[Hidden]

Well found, a good overview. Thanks

[Hidden]

I've taken the liberty of extracting some of the main points which confirm some things that are commonly known and refutes some of the other things commonly claimed.

I see there is not mention of the many varied supplements and diet regimes that might be of use.

Iron therapy

oral iron replacement is suggested if the fasting serum ferritin level ≤75 mcg/L Iron therapy should not be prescribed empirically because it may result in iron overload,

Two randomized studies of intravenous iron sucrose failed to show a benefit as did two trials of intravenous ferric carboxymaltose.

A meta-analysis found insufficient evidence to conclude whether iron is beneficial for treatment of RLS

There are no direct comparisons of intravenous versus oral iron supplementation in patients with RLS, and available data do not show clear superiority of one route of administration over the other

For most patients, because oral iron is easier to administer and safer, we suggest initial therapy with an oral regimen

Iron should be combined with vitamin C or a small glass of orange juice to enhance absorption. Iron should not be taken at the same time as calcium supplements or significant amounts of dairy products.

Intravenous iron therapy is generally reserved for patients with a serum ferritin ≤100 mcg/L, transferrin saturation <45 percent, and either a malabsorption state, complete intolerance to oral iron preparations, moderate to severe symptoms despite a trial of oral iron, or the need for a more rapid response due to severity of symptoms

Trials of intravenous iron suggest that it is effective in approximately 50 to 60 percent of patients

Nonpharmacologic Therapy

Includes -

Avoidance of aggravating factors, including consideration of withdrawal of possibly predisposing medications

Sleep deprivation is known to aggravate symptoms of restless legs syndrome (RLS) in many patients, and general principles of sleep hygiene should be reviewed.

Evaluation and treatment of other causes of sleep disruption, including comorbid sleep disorders such as obstructive sleep apnea (OSA), is also indicated

Antidepressants, neuroleptic agents, dopamine-blocking antiemetics such as metoclopramide, and sedating antihistamines (may contribute to emergence of RLS or worsening of prior symptoms

Most antidepressant classes have been associated with RLS, including tricyclics, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors

Bupropion is an alternative antidepressant that may be less likely to induce or worsen RLS

Chronic Persistent Symptoms

●For patients with very severe RLS, comorbid depression, obesity, or metabolic syndrome, a dopamine agonist is preferred over other drugs as initial therapy.

●For patients with comorbid pain, anxiety, or insomnia or a history of impulse control disorder or addiction associated with use of a dopamine agonist, we suggest starting with an alpha-2-delta calcium channel ligand.

●For most other patients, we initially try an alpha-2-delta calcium channel ligand If the first drug chosen is ineffective or poorly tolerated, then a drug of the other class should be tried.

Drug dosages should be used at the minimum dose required to control symptoms.

Patients on continuous therapy should be examined regularly (eg, every 6 to 12 months) and screened for side effects and complications such as augmentation

Less frequent side effects (of DAs) include, insomnia,

and Excessive daytime sleepiness can occur at higher doses and occasionally manifests as sudden, unexpected sleep attacks

Dopamine withdrawal syndrome can occur with abrupt discontinuation of dopamine agonist therapy. Symptoms include anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, and drug craving

Alpha-2-delta calcium channel ligands —

useful when RLS occurs in the setting of a painful peripheral neuropathy or an unrelated chronic pain syndrome and in patients with comorbid insomnia or sleep disturbance that is disproportionate to other RLS symptoms

The recommended dose of gabapentin enacarbil for RLS is 600 mg, taken in the early evening. Over 40 to 52 weeks of treatment, was - as good as - pramipexole on measures of efficacy and was associated with a significantly lower augmentation rate

pregabalin may also improve subjective and objective measures of sleep maintenance and total sleep time in patients with RLS and comorbid insomnia

The usual effective dose is 150 to 450 mg.

gabapentin beginning treatment at 100 to 300 mg in the evening ( and titrating slowly upwards

The usual effective dose is 900 to 2400 mg daily given in a single dose or divided one-third at midday and two-thirds in the evening for maintenance doses ≥600 mg daily

Intermittent Symptoms

In patients with mild or intermittent symptoms, nonpharmacologic therapies may be sufficient for symptom relief.

In other patients, we suggest use of levodopa or a dopamine agonist on an as-needed basis.

Benzodiazepines — Benzodiazepines can be useful in mild cases of RLS, The best-studied benzodiazepine in RLS is clonazepam

use of benzodiazepines for RLS is generally limited to those patients that require only intermittent therapy, or as an add-on agent in patients with refractory symptoms.

Short-acting benzodiazepine receptor agonists such as zolpidem should generally be avoided, as a high frequency of sleepwalking and sleep-related eating disorder has been reported as high as 80 percent

Augmentation

The risk of augmentation

3 to 9 percent of patients taking Pramipexole for one year

one-third of patients taking Pramipexole for two years

42 to 68 percent of patients taking Pramipexole for 8 to 10 years

Ropinirole it appears the short-term augmentation rate is similar to that of Pramipexole.

Rotigotine Augmentation has been reported in 2 to 9 percent of patients taking for one year and 38 percent of those using rotigotine for five years

The risk of augmentation increases with higher daily doses, longer duration of use, and lower iron stores

Tramadol has also been reported to cause augmentation in some patients Alpha-2-delta calcium channel ligands have not been associated with augmentation.

For more severe augmentation, switching from Pramipexole or Ropinirole to the extended release transdermal preparation, Rotigotine, can sometimes help

Alternatively, dopamine agonists can be discontinued and replaced with alpha-2-delta calcium channel ligands

We typically introduce the new drug and increase the dose to an effective level before slowly reducing the dopamine agonist and discontinuing if at all possible.

Some experts advocate a 10-day wash-out period before introducing the alpha-2-delta ligand in order to establish a baseline measure of disease severity, but this can result in increased RLS symptoms and profound insomnia during the wash-out period.

For severe, continuous symptoms despite these measures, a low dose of a long-acting opioid may be an option in selected patients.

Opioids — Opioids can be effective in the treatment of chronic and refractory RLS, particularly for patients who have not responded to other therapies.

Although low-potency opioids such as Tramadol and Codeine can be tried, most patients with refractory symptoms will require a high-potency agent such as Oxycodone or Methadone.

[Jumpey]

Thanks for posting. X