Compounding Pharmacists Help Patients Manage Complex Issues of Restless Legs Syndrome
What keeps you awake at night? Some people find themselves plagued by stress, especially when trying to fall asleep. The minute their head hits the pillow, they just can’t stop their brains from ruminating over commitments and struggles. Then there are those who may be calm and content with life—great job, no financial or family problems—yet they still struggle to fall asleep. What they may not realize is that the TV in the bedroom emits enough light to mess with their circadian cycle.
We all know the frustration of not being able to fall asleep, but for most of us, it doesn’t happen often. Imagine the impact it would have if you couldn’t get to sleep or your sleep was disrupted two to five nights every week, not temporarily, but lasting for the duration of an incurable condition like restless legs syndrome (RLS). Sure, some patients with RLS find relief with medication, but many don’t. As experts continue to evaluate this complex condition, compounding pharmacists can step in to help patients find optimal relief for restless legs syndrome.
Restless Legs Syndrome Remains Hard to Treat
Back in 2006, experts described restless legs syndrome as a common condition that was frequently unrecognized, misdiagnosed and poorly managed. Ten years later, not much has changed. It’s still called an under-recognized and misdiagnosed condition. While we have more treatment options now, it’s still hard to manage due to variation in frequency and severity of symptoms. RLS affects 5 to 15 percent of the general population, with women having double the risk as men.1 While it can begin at any age, symptoms usually progress slowly so they’re often not diagnosed until 10 or more years after symptom onset.
The Agency for Healthcare Research and Quality reports that many patients switch between treatments or drug classes either because the medication wasn’t effective or due to side effects. Surveys developed by the Restless Legs Syndrome Foundation and completed by 1,622 respondents reveal the depth of the challenge:2
- Only 9 percent stay on the same medication without any changes.
- Forty percent have tried two to five different meds—13 percent have used 7 to 10 meds.
- About 70 percent experience augmentation, a worsening of symptoms after starting medication.
- Many respondents—73 percent—said they need more effective meds.
- Nearly 25 percent reported that nothing relieves their symptoms.
Restless Legs Syndrome Associated with Major Disease
As compounding pharmacists counsel RLS patients, it’s important to keep the association between primary RLS and other diseases in the conversation. Some comorbidities, such as high blood pressure, stroke and cardiovascular disease, are probably related to the effect of RLS on sleep. For example, in January 2016, researchers from Massachusetts General Hospital reported that more than 30 percent of their patients with insomnia or RLS were also diagnosed with obstructive sleep apnea.3 But cause and effect may be different for associations reported in other recent studies:
- Patients with migraine headaches have double the risk of developing RLS and it’s likely to be more severe.4
- Nearly 40 percent of those with RLS develop psychiatric disorders.5
- Patients with iron deficiency and kidney disease have a higher prevalence of RLS.
In addition to highlighting how critical it is to assess and treat underlying conditions, such associations have some researchers wondering whether RLS should be reclassified as a spectrum disorder, with a major genetic contribution at one end and environmental factors or comorbid disease at the other.6
First-Line Treatment Recommendations
One example of the difficulty treating RLS is seen in patients with sporadic or spontaneous remission of symptoms. Medications may help, but continuous pharmacologic treatment should only be prescribed for patients who experience symptoms at least three nights each week. Guidelines developed by the International Restless Legs Syndrome Study Group advise prescribing either a dopamine-receptor agonist or an alpha 2-delta calcium-channel ligand as first-line treatment for most patients. The list of potential medication options includes:
- Dopaminergic agents: Pramipexole, ropinirole, rotigotine and levodopa-carbidopa
- Anticonvulsants: gabapentin and pregabalin
- Presynaptic alpha-adrenergic agonists: clonidine
- Benzodiazepines: clonazepam
- Iron supplements: Administered together with vitamin C for patients with iron deficiency.
- Opioids: oxycodone, codeine, methadone and tramadol—only for chronic and refractory RLS and for patients who don’t respond to other therapies.
Pramipexole and ropinirole are less likely to cause side effects than other dopamine agonists, but all of the meds in this class are associated with augmentation. When augmentation occurs, symptoms become more intense, they begin to appear earlier in the day, and RLS sensations begin to affect the arms or trunk. The good news is that augmentation is relieved when meds are discontinued. Gabapentin works well for reducing crawling, tingling and other sensations, and it’s recommended for moderate to severe RLS. Taking benzodiazepines at bedtime can help those with mild or intermittent symptoms.
Proactive Outreach Tips
Antihistamines: Outreach is especially important for patients who buy sedating antihistamine for allergy relief because they may not realize that these OTC products aggravate RLS symptoms. Even though allergies can occur all year, consider putting up a poster at the start of spring allergy season alerting RLS patients to talk to you before making a purchase.
Sleep aids: Sleep deprivation becomes a way of life for RLS patients. Along with the obvious impact on mood, cognition and job performance, lack of sleep contributes to chronic disease. Half of the RLS/WED survey respondents said their sleep is disrupted four or more days every week, while 25 percent had sleep problems two or three days weekly. It’s no surprise to learn that one-fourth of them use OTC sleep aids—which gives compounding pharmacists an opportunity to reach out and recommend safe and effective products such as melatonin and GABA.
Relaxis: This medical device may help patients fall asleep by using vibration to overwhelm RLS sensations. Patients can adjust the intensity, then it runs for 30 minutes before gradually ramping down and shutting off—hopefully after the patient is sleeping. Even if you don’t carry medical equipment, if you have the opportunity to connect with patients and their physicians, be sure they’re aware of the cost versus benefits.7
Non-pharmacologic treatments: They’re not backed by evidence-based research, but non-pharmacologic options help some RLS patients, especially those with mild symptoms.
- Sleep hygiene—Keep a regular sleep schedule, avoid caffeine after lunch and alcohol after dinner and turn off all lights and electronic equipment.
- Moderate exercise at least 30 to 60 minutes before bedtime.
- Leg massage
- Hot or cold bath
- Cognitive behavioral therapy
- Compression Stockings
Compounding Pharmacists Improve Patients’ Quality of Life
Considering the complex nature of restless leg syndrome, the potential side effects of first-line medications, and its association with multiple health conditions, chances are high that your patients with RLS haven’t been adequately counseled. Thanks to medication reviews, compounding pharmacists are quite possibly the only professional who can see the complete picture and help patients find optimal relief.
Pharmaceutica North America provides high-quality bulk APIs used to treat restless legs syndrome, as well as OTC products such as melatonin that improve your patient’s quality of life. Please contact us today to talk about how we can help meet your pharmaceutical needs.
- “Restless Legs Syndrome,” April 2016, http://emedicine.medscape.com/article/1188327-overview ↩
- “The RLS/WED Patient Odyssey,” November 2013, http://www.rls.org/file/webinars/Odyssey-Patient-Survey.pdf ↩
- “Sleep Apnea in Patients Reporting Insomnia or Restless Legs Symptoms,” January 2016, http://www.ncbi.nlm.nih.gov/pubmed/25974333 ↩
- “Restless Legs Syndrome in Migraine Patients: Prevalence and Severity,” March 2016, http://www.ncbi.nlm.nih.gov/pubmed/26998996 ↩
- “Psychiatric Comorbidities in Restless Legs Syndrome,” March 2016, http://www.ncbi.nlm.nih.gov/pubmed/27019065 ↩
- “Restless Legs Syndrome Associated with Major Diseases: A Systematic Review and New Concept,” April 2016, http://www.ncbi.nlm.nih.gov/pubmed/26944272 ↩
- “Relaxis Clinical Data,” 2012, http://myrelaxis.com/relaxis-clinical-data/ ↩