What is Dopamine Dysregulation Syndrome?

A Rare Complication of Parkinson's Disease Medications

elderly main looking at pill box
mother image/Taxi/Getty Images

Replacement of dopamine in the form of the drug carbidopa/levodopa is one of the best-established treatments in neurology, and allows patients with Parkinson’s disease some relief from their tremor and rigidity. Occasionally though, dopamine replacement comes with side effects.  The best known of these include hypermobility (too much movement) or even hallucinations.

Dopamine dysregulation syndrome (DDS) is another potential complication, occurring in about 4 percent of patients on dopaminergic therapy.

Symptoms of Dopamine Dysregulation Syndrome

The most common symptom of dopamine dysregulation is compulsive craving of Parkinson’s medication like carbidopa/levodopa.  Even if no symptoms are present (like tremor or rigidity), the patient may strongly feel that they need the medication. Others may try to simulate their Parkinsonian symptoms or bribe friends or family members in order to obtain the desired medication -- this is how strong the craving is. 

In addition, people with dopamine dysregulation syndrome may feel grandiose or euphoric, and without the medication, they may feel depressed or fatigued. Also, impulse control problems, like compulsive gambling or shopping, eating disorders or other addictive behaviors, may occur, as a result of dopamine dysregulation. More simple compulsive behaviors, such as collecting objects or compulsively placing objects in a line, may also appear. Severe symptoms like psychosis are also possible in this syndrome

What Causes Dopamine Dysregulation Syndrome?

Dopamine is connected with our reward system at the base of the frontal lobes, including the ventral tegmental area. In fact, addictive drugs, such as cocaine, stimulate dopamine release in this area.  Dopamine activity in this area of the brain has been believed to cause dopamine dysregulation syndrome.

That being said, the exact mechanisms are not well understood. Furthermore, if dopamine is so important to both movement and the reward system, it's perhaps surprising that DDS is relatively uncommon.

When an addictive drug is given, the reward system can habituate to the amount of reward, requiring greater quantities to give the same effect. We know that this is also true of dopamine therapy in Parkinson’s -- greater doses will ultimately be needed to require the same effect. While some of this is very likely due to disease progression, some scientists question if this increased need may reflect a kind of habituation, which in the reward system, may result in a kind of craving.

Who Gets Dopamine Dysregulation Syndrome?

The rarity of DDS suggests that most people are relatively protected against the disorder, while others may have risk factors for developing the disorder. Men with early disease onset may be at a higher risk.  Previous compulsive behaviors, such as substance abuse, is one of the greatest risk factors.

 

How is Dopamine Dysregulation Syndrome Treated?

Because patients with DDS basically have an addiction to a drug that they also require to function, the best treatment involves strict dosages of dopamine or dopamine agonists (medications that activate dopamine receptors).  Dysregulation symptoms will decrease as the medication dose is lowered.  As with other addictions, social support will be needed to help ensure that medications are taken as prescribed and to manage other compulsive behaviors.  In extreme cases, antipsychotics may be useful to manage aggression or psychosis, though these increase the risk of worsening symptoms of Parkinson’s disease. 

Bottom Line

Dopamine is a complicated neurotransmitter impacting our movements, our motivation, and our reward system in ways that we still don’t fully understand, despite decades of study. While dopamine dysregulation syndrome is not common in Parkinson's disease, it can occur, and the best intervention is one that is early and supported by the affected person's doctor, caregiver, and/or loved ones. 

Sources:

Cilia, R., et al.  (2014). Dopamine dysregulation syndrome in Parkinson’s disease: from clinical neuropsychological characterization to management and long-term outcome. Journal of Neurology, Neurosurgery, & Psychiatry, 85(3):311-8.

Evans, A.H., Lees, A.J. (August 2004). Dopamine dysregulation syndrome in Parkinson's disease. Current Opinion in Neurology, 17 (4): 393–8.

Lawrence, A.D., Evans, A.H., Lees, A.J. (October 2003). Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry? Lancet Neurology, 2 (10): 595–604.

Pezzella, F.R., et al. (January 2005). Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson's disease". Mov. Disord. 20 (1): 77–81.

Continue Reading