Restless legs syndrome (RLS) is a common neurological disorder, affecting up to 15% of people in our community. In up to 2.5% of our community the condition is so severe that quality of life is adversely affected.
The cause of this condition is unknown. Central dopaminergic pathways (dopamine is a neurotransmitter, a chemical carrying messages between nerves) have been implicated in this disorder, and ‘dopaminergic’ medications are first-line drugs when it comes to treating RLS. Dopaminergic neurological pathways beyond my understanding are also important in mechanisms of behavioural reward and reinforcement – ie you perform an action, it feels good so you do it again. Dopaminergic medications interfere with these pathways, and in some people this leads to reduced ability to control impulses towards the performance of personally destructive behaviours.
In the last five years or so, two relatively – new dopaminergic medications have become available in Australia for treatment of restless legs syndrome. The first of these, ropinirole, is available on private script only. The most recent, pramipexole, is available on the PBS for patients who score more than 21/40 on the International Restless Legs Syndrome Rating Scale. With the availability of pramipexole, previously used in the USA for treatment of RLS (and also used in Parkinson’s disease) has come increasing interest in the question of whether these medications really do cause reduced impulse control, and correspondingly increased compulsive behaviour. Is this true? Is it a problem?
A colleague of mine in at the Melbourne Sleep Disorders Centre has done some excellent, recent, local epidemiological work in this field. Similar work from the Mayo Clinic was published in Sleep journal last month. The findings were similar to those my colleague presented at the Australasian Sleep Association conference in Melbourne in October. They suggest that the phenomenon of reduced impulse control in patients with RLS on dopaminergic medications is real, and is a problem.
The recently - published article surveyed 100 consecutive patients with RLS who had been treated with dopaminergic medications. (Not all of these patients had been treated with pramipexole or ropinorole. Other medications included levodopa, bromocriptine, pergolide, cabergoline, rotigotine patch and apomorphine). They also surveyed 275 patients with obstructive sleep apneoa, as a control group, who had no symptoms of RLS. A smaller group of patients with RLS on no dopaminergics was also included (52 patients).
A variety of compulsive behaviours were screened for, using a mix of commonly used and validated screening tools (for compulsive gambling) and home-made questionnaires. Information was sought about compulsive gambling, shopping, eating, hypersexuality and ‘punding’. I had no idea about this last verb, but it refers to repetitive, complex, stereotypical but purposeless actions – for example grooming, cleaning, hording, operating technical equipment with no goal. A self – completed questionnaire was followed by a telephone interview to try to heighten the rigour of the process (and make it more specific for real problems).
The end result was that 17% of patients in the RLS group treated with dopaminergic agents displayed problems with impulse control. Only 6% of the OSA control group displayed similar behaviour. This 11% difference was statistically significant. In particular, compulsive shopping (9% vs 0.7%), gambling (5% vs 0.4%) and punding (7% vs1%) were behaviours where the striking discrepancy in prevalence was also statistically significant.
Twelve of the seventeen patients displaying difficulty with impulse control were taking pramipexole at the time of symptom onset, and fifteen of them had taken that medication at some time. Five were taking ropinorole at time of symptom onset.
These behaviours usually began several months after onset of therapy (mean of 9.5 months) . Their frequency may have been underreported because of study design (perhaps they should have surveyed husbands/wives/partners as well).
The case reports provided in the Sleep journal study serve to underline what is at stake here, and emphasise why it is important to aggressively screen patients on these medications for these bevhaviours – behaviours to which they will seldom readily confess. Sometimes stories communicate better than figures:
Case Report: A 47 yr old woman reported concerning behaviours after she had been taking pramipexole at 0.50mg daily for 6 months. She lost an estimated $5000 on purchases from the shopping channel (‘ugly clothes and jewelry that I didn’t even need’) and set her alarm clock for the early morning hours ‘because I just couldn’t miss a sale’. She had food binges, eating an entire pizza or a dozen donuts at one sitting ‘even though I wasn’t hungry’. Sometimes she would stay up ‘all hours of the night’ cross stitching. Finally, she reported ‘being more risky’ by performing sexual acts in public. Although present for almost 2 years, these behaviours resolved completely in 1 to 2 months after pramipexole was discontinued.
Case Report: A 59 yr old man is dealing with ongoing litigation related to inappropriate sexual behaviours involving the Internet that prompted police to raid his home, much to the shock of his wife and grandchildren. He gained more than 200pounds with food binges, his wife constantly returned unneeded purchases to the store, asnd he spent 10 to 12 hours per day on the computer in chat rooms, playing games and viewing pornography. All of the behaviours started within a year of his taking ropinirole, 4.0mg daily, and resolved quickly when he was taken off the medication.
Pramipexole can be tremendously effective in treatment of restless legs syndrome. The potential for associated problems with impulse control must not, however, be taken lightly.
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