Q:  Restless Leg Syndrome & Dopamine

I have been diagnosed and treated for Bipolar II since 1997. I have recently been diagnosed with Restless Legs Syndrome and my psychiatrist gave me Clonazepam to help me sleep and for anxiety. It worked! In the meantime, I did some research on restless legs syndrome and discovered that doctors suspect a deficiency of Dopamine receptors may be the cause.  I also have Reynauds' Phenomenon, Essential Tremors and Bipolar.  All of these seem to have a connection to the same problem. Have you seen patients who have these same problems together? Also, I recently had to take Zocor for cholesteral and many symptoms associated with my illnesses got worse. Why? Have you heard of anyone else who experienced increased problems while taking Zocor? Does it mess with dopamine? Thank you for taking the time to answer my questions.


Dear Ms. C.-

Well, this is quite interesting. In particular, this reaction to the Zocor. I was once involved in a research trial on lowering cholesterol and heart disease risk and I believe I recall from that study that "restless legs" was indeed associated as a symptom, even though we were using a different kind of cholesterol-lowering treatment. In any case, it seems as though you are observing a direct connection. I looked up the relationship between cholesterol reduction and dopamine levels. Sure enough, there is at least one article describing this (Ormiston et al).

As for the mechanism of "restless legs syndrome", you are right, this is definitely thought to be associated with dopamine. As you may know, there is even a treatment for it, using medications which increase dopamine. However, as dopamine is known to be part of what makes patients with bipolar disorder of psychosis (at least in bipolar I), we are generally hesitant to use these medications and bipolar disorder (even though they have some recent data showing benefit in patients with bipolar depression). All that is to say that dopamine is definitely involved, although I am not certain whether it is a "deficiency of receptors": the mechanism may not be quite that clear. Here is some dense medical jargon along those lines, from "e-medicine". 
 

Pathophysiology: Pathogenesis of RLS is unclear. Ekbom originally proposed that it was mainly the result of accumulation of metabolites in the legs because of venous congestion. Peripheral nerve abnormalities also have been proposed, but no associated structural changes in nerve endings have been identified.

RLS also has been linked to dopaminergic or opiate abnormalities. Centrally acting dopamine receptor antagonists reactivate symptoms when given to patients with the syndrome. Results of single-photon emission computed tomography (SPECT) have suggested deficiency of dopamine D2 receptors. Sympathetic hyperactivity also has been implicated on the basis of observations that sympathetic nerve blockade relieves periodic limb movements of sleep and that alpha-adrenergic blockers improve symptoms of RLS. Studies also have suggested possible underactivity of the serotonin and gamma-aminobutyric acid (GABA) neurotransmitter systems.

eMedicine - Restless Legs Syndrome Article by Juan Latorr 

  Thank you for this opportunity to continue my own education.

Dr. Phelps