RLS and PLMD: Part II

For most leg jerk medications, it is interesting to listen to patients describe how they think the drug works, especially for the dopaminergic drugs we talked about on the last post as well as the other meds to be discussed shortly. Most RLS/PLMD patients have some degree of confusion about how the leg movements are affecting them; but among those who report difficulty falling asleep, they possess the expectation that leg jerk meds must provide a sedative-like effect. However, in most instances the drug provides nothing like a sedative effect. Rather the pill removes the uncomfortable sensations at bedtime, which then permits the patient’s natural sleepiness take over. This natural wave of sleepiness was always present but it had been masked by the RLS symptoms in particular. Once the drug eliminates RLS, the wave laps upon the shore, and the patient falls asleep. Most patients are surprised by this sequence, even though they were told the drug is not a sedative. That’s why the medication is taken before bedtime, not at bedtime, so there is an interval or window of opportunity for this scenario to play out.

Opiates are another well-researched category of drugs to treat RLS/PLMD, but which abruptly raises red flags in many peoples’ minds, because it is a narcotic and most frequently associated with either pain relief or addiction or both. The good news about opiates is they work at low dosages or they do not seem to work at all. Thus, the chances of receiving prescriptions with increasingly larger dosages of medications would be most unlikely. Moreover, opiates are very well researched medications for RLS/PLMD, and at one major university, Johns Hopkins School of Medicine, there has been a great deal of research and clinical use of many opiates to treat RLS/PLMD, including use of a surprising option in the form of low dose Methadone.

Oxycodone pills, the most commonly used opiate for RLS/PLMD, are prescribed in very low doses compared to someone with a broken ankle. The latter patient would receive a bottle of 60 pills of 5 mg Oxycodone pills for one week of pain relief, taking up to 8 to 10 pills per day. In contrast, 60 pills for an RLS/PLMD patient could last 1 to 2 months. In my own practice, I start many patients with extremely low doses of oxycodone, such as 1.25 to 2.50 mg. These values may be approximations as there is no scored quartering line on the pill to divide into equal portions, not to mention some of the irregularities in the way the medicine itself is unevenly distributed into the pill. Nevertheless, I have seen many very satisfied patients using this low dose approach to oxycodone.

Often, the patient will start at 2.5 mg and then go to 5.0 or 7.5 mg. Another group will eventually increase to 10 mg. But, I can count on one hand and not use all my fingers to note the few people who might regularly need 15 to 20 mg of Oxycodone at bedtime, and one of these patients turned out to be a doctor-shopping, drug addict years ago.

So, abuse potential is very low, because the patient cannot persuade the sleep physician to prescribe more since it is unusual for more to be needed. As such, a sleep doctor can always repeat a sleep study with the patient using his or her current dosage of oxycodone (or for that matter any other drug for RLS/PLMD) and then make the informed decision to increase the opiates or try a different medication.

Oxycodone is safe, but it can produce the troubling side-effect of constipation, which can be effectively treated with over the counter remedies, albeit stewed prunes and prune juice may be especially cost-effective. Opiates obviously can impart some sedating feelings, especially in the first few days or weeks as the patient adapts to the medication. However, because opiates actually eliminate RLS feelings and PLMD leg jerks, this side effect of drug-induced sleepiness is probably not a major component of how the pill operates in your body.

Several other opiates are used including Hydrocodone and Methadone. Propoxyphene (Darvon) was a very effective option but was taken off the market. Codeine seems to be less effective and has more digestive side-effects. Tramadol, an opioid agonist (acts like an opiate) has received recent attention and may confer some benefits.

One of the strongest reasons to consider opiates is they seem to produce far less augmentation problems, that is, they do not produce as much of the paradoxical response in which the drug makes the RLS or PLMD worse. Then again, opiates have the non-symptomatic side effect of being verboten among people working in various jobs, such as those related to transportation industries or in security fields. The mandatory drug testing in these enterprises makes it impossible for someone to consider even low dose opiates.

The last main category are those related to a type of receptor in the brain known as GABA. These drugs include Neurontin, Lyrica and Horizant, and the first two have some anti-seizure properties and the third and more recent drug was specifically designed as a long-acting medication for RLS. These medications initially were not widely in use or deemed to be very effective. But in the past decade, we have seen not only an increase in their prescriptions, but also more evidence showing greater effectiveness than once thought.

Neurontin (gabapentin) is the least expensive of these types of drugs and works very well in many patients, but a major drawback is the unusual dosing schedule. Despite requiring total dosages of about 1200 to 1800 mg, the drug is not taken in doses larger than 600 mg at one time when treating RLS/PLMD. Thus, for 1200, you would take 600 at dinner time and then 600 at bedtime. For 1800, you would add the third dosage (the first one in the day) around lunch time. The research that demonstrated the greater effectiveness of this split dosing schedule was in part what led to the development of a long-acting version of gabapentin-like drug, called Horizant.

Some people imagine that a total dosage of Neurontin 1800 mg is a large amount when actually it remains in the low to medium range. Compared to chronic pain patients suffering from various conditions, it is not uncommon to see total dosages between 3600 to 4500 mg. Regardless, the split dosing schedule is the main barrier for many patients, because of the inconvenience or hassles in maintaining the correct timing during the day for something that is occurring at night. Taking something at lunch requires the individual to devise a well-constructed system to plan out the dosing schedule. Clearly, the more effective the drug works on the RLS/PLMD, the patient will be more motivated to maintain this schedule.

Lyrica is in the same family of drugs and may also may work well in some folks, but it is clearly associated with potentially large weight gains, and sometimes rapid weight gain; many folks stop using the drug within the first 10 to 30 pounds of extra weight. A recent research study showed Lyrica was as effective as Mirapex; and in the protocol, patients started out with 75 mg before bedtime and then advanced to 150 mg and finally to 300 mg, all occurring in less than 2 weeks. The drug was not necessarily used right at bedtime but rather from 1 to 3 hours before bedtime.

Horizant, the most recent drug in this family, has the very interesting advantage of taking the properties of Neurontin and turning it into a long-acting agent. The medication is only used once per day around 5 pm or dinner time or thereabouts and it lasts through the night. Nearly everyone who uses Horizant reports that it works well, and they can usually detect the improvement in just a couple days, often five days most. The oddest thing about the drug, from our clinical experience, is the lack of large objective improvements on follow-up sleep studies even though the patient is reporting excellent subjective results. With the dopaminergic and narcotic drugs, it is very common to see the number of leg jerks drop down to a rare frequency, but we have not seen that degree of objective improvement with Horizant. Yet, despite the complexities of pricing as well as dealing with insurance coverage issues, Horizant seems to be an excellent choice for many patients. Generally, the patient must fail two other RLS/PLMD drugs and then insurance will provide coverage for Horizant, but even then, the cost may still be pricey.

Numerous other medications are in use for RLS or PLMD, but the ones discussed above are the most established and effective. Most sleep specialists keep current on medication research for movement disorders, because most centers see at least 10% of patients with these problems. Unfortunately, many physicians, even a fair number of sleep professionals, continue to prescribe 3rd or 4th line agents, notably benzodiazepines such as Valium or Clonazepam or sedatives such as Ambien without having taken the time to work through the evidence-based drugs described above. While these agents may work for some patients, they are very poor choices, because they rarely eliminate the leg jerks, and they often lighten one’s sleep to a less restorative state.

If your sleep disorders are RLS or PLMD or both and nothing else, then medication may be the only treatment you will need for what are called independent movement disorders. However, with the advent of pressure transducer technology that measures breathing in a much more precise manner, we see many more cases of limb movement disorders that co-occur with sleep apnea. Many of these patients were told the RLS or PLMD was an independent disorder for which they had been receiving treatment for years until they completed a more sophisticated sleep study. Nowadays, many patients with these co-occurring problems use both PAP therapy and drugs, and by doing so they report the combination of treatment dramatically improved their results compared to either treatment used alone.

To close out Part II, I will comment on medications that seem to worsen leg jerks, the most common of which are antidepressants. These drugs are in common use today and are frequently prescribed by primary care physicians not just psychiatrists or psychologists who now hold licenses to prescribe psychotropic medications. Two of the more common findings in antidepressant-induced leg movements are their more rapid frequency and the lack of arousals not consistently showing up in the brain waves. Both these points lead to considerable confusion in treating patients, because on the one foot the overwhelmingly high frequency makes it seem implausible the drug is not disrupting sleep, but on the other foot the absence of the arousal activity suggests sleep disruption is minimal or non-existent. Thus, the most common strategy for these antidepressant effects is to suggest to patients to try another medication, especially if they are dissatisfied with the impact on their depression. In some cases, we will put patients on the regular RLS/PLMD drugs to treat these leg jerks, but I will mention from our own experience and the lack of research on the topic, it is not very clear how well this standard approach works in patients with antidepressant-induced leg jerks.

In Part III, we will look at vitamin and mineral deficiencies and supplements as well as the new tool called the pneumatic compression device, the same gizmo used in hospitals to prevent blood clots from forming.


Barry Krakow MD

Author

Dr Krakow’s 27 years of sleep research have focused on the complex relationship between physiological and psychological sleep disorders. Dr Krakow currently operates private sleep medical center, Maimonides Sleep Arts & Sciences, Ltd., and serves as Classic SleepCare’s paid Medical Director.



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