Depression in Restless Legs Syndrome (RLS) from Dopamine Agonist Discontinuation

Dopamine agonist medications including pramipexole (Mirapex®), ropinirole (Requip®), and rotigotine (Neupro®) had been first-line treatment for restless legs syndrome (RLS), but after more than two decades of use in this condition, it is now apparent that they should no longer be used to treat RLS with rare exception, due to risk of inevitable augmentation, impulse control disorders, chemical dependence, and overall disruption of the dopaminergic system in the brain. However, the negative effects of these drugs on mood often go unnoticed, particularly after successful tapering off and elimination of the drug as a treatment in individuals with augmentation.
Watch this video explaining what augmentation is:
• What is Augmentation i...
Andy Berkowski, MD of ReLACS Health reports on the ways in which these medications-and the withdrawal from them-lead to dopamine dysfunction in the brain. The impairment to the brain's natural dopamine system can affect sensations, movements, decision-making, and mood. Here, loss of appropriate dopaminergic function can lead to anhedonia, which is derived from the Greek, meaning loss of enjoyment in normally pleasurable activities. This causes a person to be resistant to the common activities that typically produced emotional enjoyment. Despite the improvement to RLS and sleep quality after recovery from dopamine agonist withdrawal, for months thereafter, some patients lose the enjoyment of life and this can lead to other symptoms of depression or even thoughts of suicide.
Unfortunately, the easiest solution is to restart dopamine agonists, which would stop the withdrawal and natural recovery process and give the artificial dopamine stimulation back, which is what the withdrawing brain craves. However, this will just set the individual back to where they were during augmentation and chemical dependence on these medications. There are no well-studied solutions currently. From a lifestyle standpoint, setting goals and motivating oneself to engage in social interaction and normally pleasurable activities can be a start. Therapy from a licensed mental health profession can be essential and free of drug side effects, more importantly. These individuals can help with medical doctors to monitor for increasing levels of depression, including self-harm or suicidal thoughts. Medications can be used to combat the effects of depression, specifically bupropion (Wellbutrin®), which is the only RLS-neutral antidepressant. Other classic SSRI or SNRI medications may be needed, even at the risk of worsening RLS slightly, which can be overcome with other RLS treatments for the sake of improvement to mood. In all, this is yet another reason why providers should stop prescribing dopamine agonists for RLS.
If you are someone you know expresses thoughts of self-harm or suicide, this is a medical emergency, please call the Mental Health Crisis Hotline at 988 anywhere in the U.S. or go to the nearest psychiatric emergency department.
You may read more about why dopamine agonists are bad for RLS in A ReLACSing blog:
www.relacshealth.com/blog/v3h...
To watch how these medications lead to impulse control disorders:
• Impulse Control Disord...
For an overview of how to taper off dopamine agonists:
• How to Taper off Dopam...
For those that are unsure of what RLS is:
• Does Restless Legs Syn...
Despite affecting about 5% of the U.S. population, RLS is highly ignored in the medical field. Read an analysis of why this may be: www.relacshealth.com/blog/a-r...
In Memoriam Robert H. May his soul rest in peace.

[@monicamestas7566]

Thank you, Andy. Your videos are so great. I have learned so much about RLS... now that I'm 68. I guess we just didn't know as much 30 years ago. I've battled depression most of my adult life. Didn't know about the dopamine agonist-depression connection. I already had depression but sounds like Requip (Ropinirole) didn't help the situation. Clears up a lot of things. Didn't even know my "twitches" had a name until I was 45ish, then took Requip for 15 years or so. Now, thank goodness, I've been taking Methadone since 2016. At 50, I was finishing my bachelor's degree, which I'd begun many years earlier. Interestingly, In one of my writing classes, I wrote a paper called "Requip: A Love-Hate Relationship. I wish I could find it now ;)

[@monicamestas7566]

Oh, now I'm realizing you said it's the discontinuation of dopamine agonists that initiates depression. It's late at night. I'll have to watch your video again in the morning ;)

[@andyberkowskimd]

Thanks for sharing your story

[@sylvieferland3317]

my doctor didn't know about the bad effects of dopamin agonists. now i take 1 mg mirapex , I have augmentation and Ican't stop the drug. It is already depressing

[@andyberkowskimd]

Sorry to hear about your struggles. As I have mentioned in other videos, in general, those struggling with RLS need to find a specialist with updated knowledge of RLS. Dr. John Winkelman's publication a few months ago suggests that even just following the guidelines makes a huge difference: academic.oup.com/sleep/article-abstract/45/7/zsac108/6582621?redirectedFrom=fulltext&login=false The RLS Foundation has a list of Quality Care Centers and providers who have specified that they can manage RLS: www.rls.org/treatment/find-a-healthcare-provider

[@airworksgreat]

I am going to see the neurologist today first time to diagnose RLS after family doctor referral. I have been on and off lyrica 50mg 3 month . 3 month on 1 month off then symptoms come back so i took it for 2 days now. Do you think wellbutrin will help my RLS? I had bern on 1 year before RLS starting but off the wellbutrin thought it was the cause of the RLS . Just my thoughts not sure. I dont want to go DA.

[@andyberkowskimd]

Wellbutrin has been tried in the treatment of RLS but did not show a clear benefit. It is considered "RLS-neutral" unlike most other antidepressants that tend to worsen RLS. www.jabfm.org/content/24/4/422.long

[@user-lo4lq9gz3u]

Thank you for the videos you're making I've been suffering with RLS for about 10 years and so has my dad my dad is 89 years old he gets no sleep is lake jerks all night he has a lot of pain and so do I where can somebody help me and give me information of a doctor in Brooklyn that can help me and my dad

[@andyberkowskimd]

Providers are often listed at the RLS Foundation rls.org by state and that is a good start.

[@HarrisCassie]

I was on cabegoline for high prolactin levels and I have been off of it for 8 weeks and now I suffer from anxiety. Any tips? Am I going through withdrawal?

[@andyberkowskimd]

Cabergoline is a slightly different class than the non-ergotamine dopamine agonists that have traditionally been used for RLS. It seems to reason that augmentation and dopamine system dysfunction including mood symptoms when withdrawn from ergotamine dopamine agonists like cabergoline could be similar to what we see from these RLS dopamine agonists. There are not studies on how to handle mood symptoms from dopamine agonist withdrawal long term so this must be managed by medical professionals like other forms of depression or anxiety. The problem is that most antidepressants (SSRIs and SNRIs) typically worsen RLS so some patients are between a rock and a hard place.

[@ihague4568]

I'm not sure if 'damage' is the right word when referring to the effects of dopamine agonists on the dopamine system. There is no evidence that dopamine agonists (like pramipexole) damage the dopamine system. In fact there is more evidence to the contrary (neuroprotective effects). Of course there are neurochemical adaptations that occur with dopamine agonists. Similarly, there is withdrawal from caffeine, but no evidence that caffeine damages the dopamine system. Caffeine too is neuroprotective.

[@andyberkowskimd]

There is substantial evidence that dopamine agonists lead to augmentation with long-term use, or a worsening of RLS beyond what can naturally occur. This study references many of the studies that have demonstrated augmentation: www.ncbi.nlm.nih.gov/pmc/articles/PMC8842153/ Patients on these medications, even for other conditions like Parkinson Disease, can develop impulse control disorders at high rates. One example: www.neurology.org/lookup/doi/10.1212/WNL.0000000000002803 There is a growing consensus that the adaptations of the central nervous system to dopamine agonist exposure are irreversible, and there is not full recovery to baseline after discontinuation of these medications, months and years later. Patients exposed to dopamine agonists may also be less responsive to generally effective treatments. www.sciencedirect.com/science/article/pii/S1389945718305094?via%3Dihub

[@foetsak221]

​​​@@andyberkowskimdHi Andy. I've currently been on Pramipexole for 2 months on half a tablet of 88 mico grams a day before bed that seems to be enough for controlling the RLS . I've heard that buprenorphine akso works ... would this be a better option and also for reduced risks of argumentation.. thankyou

[@wmrajput]

I looked at the Spanish study. The two weeks washout period for some one who has been on DA doesn't seem long enough at all. I personally came off ropinirole and two weeks is hardly enough time. I am not an expert at reading studies, but I dont know much financial interest the sellers of horizant had in funding the study. In my personal experience after completely coming off ropinirole I did not return to the pre DA levels of rls, but it could just be disease progression with age.