Dopamine agonists for restless legs syndrome? There may be trouble ahead

Ben is a self-employed plumber in his mid-forties and comes in to see you with his wife, Emma. The atmosphere is a bit frosty. The triage booking note just says ‘personal’. Note to brain to tread carefully here….

Ben sighs. Despite plenty of work, he’s struggling with his finances, is in debt and is pretty down. ‘She’s worried about my gambling. It’s under control, I just need to claw some back’. It becomes clear Ben hasn’t got a great deal of insight into his gambling. The debt is significant and he’s chasing losses. Oddly his problem gambling seems to have come on quite quickly and completely out off the blue. There appears to be no other stressors or triggers for this. Emma is visibly upset; ‘Do you think it’s that new medication he was put on?’. 

It turns out Ben had been put on ropinirole a few months back for some really troublesome restless legs syndrome (RLS). He is delighted with the improvement in his RLS symptoms, his sleep is better and he has much more energy in the day. But shortly after starting the ropinirole he started gambling. Previous to being started on ropinirole, he had no problems with gambling, and had no history of mental health problems or risks for problem gambling.

Emma is right. It is indeed likely that the medication is causing his problem gambling, and unfortunately Ben has developed a side effect of dopamine agonists, namely an impulse control disorder - a range of distressing pathological behavioural changes including impulsive gambling, hyper-sexuality, binge eating and impulsive shopping. The risks of impulse control disorders with dopamine agonists, and the lack of awareness of this side effect, have been recently publicised in the press. 

RLS is a common condition, but for most people the symptoms are mild and intermittent. However, for those who get more persistent and severe symptoms it is a miserable condition which can have a significant impact on sleep and mental health. The key secondary (potentially reversible) causes are iron deficiency and drugs (notably antidepressants, dopamine antagonists e.g. prochlorperazine, and antihistamines). Non-drug options should be explored first (click here for good info from RLS-UK), stopping (if possible) causative medications, as well as iron replacement if ferritin is ≤75mcg/L or TSATs <20%.

But for some medications may need to be considered. Historically dopamine agonists e.g. ropinirole and pramipexole have been used first line. Whilst effective initially, there is increasing concern about the long term effectiveness of these drugs, and their side effect profile. Augmentation is an increasingly well recognised phenomenon - whereby previously effective doses are ineffective and can even exacerbate the symptoms, leading to higher and higher dose requirements. 

Then there are the impulse control disorders. Probably more widely known about in the context of prescribing dopamine agonists for Parkinson’s Disease, impulse control disorders are just as much a risk when prescribed for RLS - this is a message that has been slow to reach us in Primary Care, as has the message that dopamine agonists should not be used first line for RLS anyway. BMJ Best Practice recommends gabapentinoids first line for persistent RLS, as does the recently published American Academy of Sleep Medicine guideline which also specifically recommends against standard use of dopamine agonists.

Why are these important side effects of dopamine agonists poorly recognised? First, despite RLS being a common condition we have no NICE guideline so practice is variable. Second, we have had no recent MHRA warnings on the risks, although it sounds as though a review is now underway. Finally, the dopamine agonists are licensed for use in RLS, and have a designated dose structure in the BNF, where as the gabapentoinds don’t. Believe me, I am no fan of gabapentinoids, and they obviously have their own risks, but in the context of RLS the benefit/risk equation seems more favourable than for the dopamine agonists.

So what do we do for Ben? Despite the benefit to his RLS we need to get Ben off his ropinirole, alongside supporting him with practical measures to help manage his problem gambling whilst he gets off the drug. Getting off the ropinirole is not going to be easy - he is likely to get rebound symptoms, which can be very unpleasant for some, so some urgent advice and input from Neurology will be needed to help make that transition. However, the good news is that his impulse control disorder should settle.