Dopamine Agonist/Levodopa Combo Linked to Compulsions

SAN DIEGO — The specific drug combination of a dopamine agonist and levodopa may trigger the onset of pathological behaviors, including compulsive gambling, hypersexuality, and compulsive shopping in a subset of patients with Parkinson's disease, according to the results of two independent investigations on a total of 485 patients presented at the annual meeting of the American Academy of Neurology.

“Although since 2000 there have been case reports [of pathologic behaviors], these are the first systematic detailed evaluations of these patients,” said Dr. Oksana Suchowersky of the University of Calgary, Alberta, Canada. In her study, 188 patients with Parkinson's disease (PD) were surveyed for difficulties with gambling. Twelve patients met DSM IV criteria for pathological gambling, equivalent to a lifetime prevalence rate of 6%, compared with 1.5% in the general population.

All patients who developed pathological gambling had been recreational gamblers before starting PD medications, and all had been treated with levodopa plus a dopamine agonist, rather than with levodopa (0 of 93 patients) or bromocriptine (0 of 14 patients) monotherapy. The risk of developing pathological gambling appeared to be a class effect of the dopamine agonists, with no significant differences among those treated with pramipexole (10%), pergolide (17%), or ropinirole (17%).

Dr. Valerie Voon, a psychiatrist who conducted research at the Toronto Western Hospital Movement Disorders Centre, investigated pathological gambling, hypersexuality, and compulsive shopping in 297 patients with PD. She found that overall lifetime prevalence (which includes both past and current behaviors) for the group was 6%, which increased to 16% in patients taking levodopa and dopamine agonist in combination. The lifetime prevalence was 3.4% for pathologic gambling, 2.4% for hypersexuality, and 0.7% for compulsive shopping; 10%–20% of patients exhibited more than one disorder.

One hypothesis is that these obsessive behaviors reflect excessive stimulation of the limbic reward system in susceptible individuals. Risk factors that may increase susceptibility to compulsive behaviors include younger age of PD onset, novelty-seeking personality traits, and history of alcohol abuse. Stage of disease was ruled out as a risk factor.

These findings suggest that clinicians should regularly query patients with PD and family members about excessive behaviors, which may take the form of hobbies, collections, sexual behavior, or shopping. Early identification can help physicians make adjustments that may rectify the problematic behaviors, including switching dopaminergic agonists, discontinuing therapy if possible, or even substituting deep brain stimulation for long-term dopaminergic therapy. The latter option should be used with caution, since Suchowersky found that 5% of 39 deep brain stimulation patients actually developed pathologic gambling after surgery.

Left unchecked, serious psychosocial consequences may result from these behaviors, including isolation, shame, depression, marital discord, and suicidal thoughts. Among Dr. Voon's patients, pathologic gambling led to a mean loss of $125,000, while some of Dr. Suchowersky's patients “literally lost the farm.”

SAN DIEGO — The specific drug combination of a dopamine agonist and levodopa may trigger the onset of pathological behaviors, including compulsive gambling, hypersexuality, and compulsive shopping in a subset of patients with Parkinson's disease, according to the results of two independent investigations on a total of 485 patients presented at the annual meeting of the American Academy of Neurology.

“Although since 2000 there have been case reports [of pathologic behaviors], these are the first systematic detailed evaluations of these patients,” said Dr. Oksana Suchowersky of the University of Calgary, Alberta, Canada. In her study, 188 patients with Parkinson's disease (PD) were surveyed for difficulties with gambling. Twelve patients met DSM IV criteria for pathological gambling, equivalent to a lifetime prevalence rate of 6%, compared with 1.5% in the general population.

All patients who developed pathological gambling had been recreational gamblers before starting PD medications, and all had been treated with levodopa plus a dopamine agonist, rather than with levodopa (0 of 93 patients) or bromocriptine (0 of 14 patients) monotherapy. The risk of developing pathological gambling appeared to be a class effect of the dopamine agonists, with no significant differences among those treated with pramipexole (10%), pergolide (17%), or ropinirole (17%).

Dr. Valerie Voon, a psychiatrist who conducted research at the Toronto Western Hospital Movement Disorders Centre, investigated pathological gambling, hypersexuality, and compulsive shopping in 297 patients with PD. She found that overall lifetime prevalence (which includes both past and current behaviors) for the group was 6%, which increased to 16% in patients taking levodopa and dopamine agonist in combination. The lifetime prevalence was 3.4% for pathologic gambling, 2.4% for hypersexuality, and 0.7% for compulsive shopping; 10%–20% of patients exhibited more than one disorder.

One hypothesis is that these obsessive behaviors reflect excessive stimulation of the limbic reward system in susceptible individuals. Risk factors that may increase susceptibility to compulsive behaviors include younger age of PD onset, novelty-seeking personality traits, and history of alcohol abuse. Stage of disease was ruled out as a risk factor.

These findings suggest that clinicians should regularly query patients with PD and family members about excessive behaviors, which may take the form of hobbies, collections, sexual behavior, or shopping. Early identification can help physicians make adjustments that may rectify the problematic behaviors, including switching dopaminergic agonists, discontinuing therapy if possible, or even substituting deep brain stimulation for long-term dopaminergic therapy. The latter option should be used with caution, since Suchowersky found that 5% of 39 deep brain stimulation patients actually developed pathologic gambling after surgery.

Left unchecked, serious psychosocial consequences may result from these behaviors, including isolation, shame, depression, marital discord, and suicidal thoughts. Among Dr. Voon's patients, pathologic gambling led to a mean loss of $125,000, while some of Dr. Suchowersky's patients “literally lost the farm.”

SAN DIEGO — The specific drug combination of a dopamine agonist and levodopa may trigger the onset of pathological behaviors, including compulsive gambling, hypersexuality, and compulsive shopping in a subset of patients with Parkinson's disease, according to the results of two independent investigations on a total of 485 patients presented at the annual meeting of the American Academy of Neurology.

“Although since 2000 there have been case reports [of pathologic behaviors], these are the first systematic detailed evaluations of these patients,” said Dr. Oksana Suchowersky of the University of Calgary, Alberta, Canada. In her study, 188 patients with Parkinson's disease (PD) were surveyed for difficulties with gambling. Twelve patients met DSM IV criteria for pathological gambling, equivalent to a lifetime prevalence rate of 6%, compared with 1.5% in the general population.

All patients who developed pathological gambling had been recreational gamblers before starting PD medications, and all had been treated with levodopa plus a dopamine agonist, rather than with levodopa (0 of 93 patients) or bromocriptine (0 of 14 patients) monotherapy. The risk of developing pathological gambling appeared to be a class effect of the dopamine agonists, with no significant differences among those treated with pramipexole (10%), pergolide (17%), or ropinirole (17%).

Dr. Valerie Voon, a psychiatrist who conducted research at the Toronto Western Hospital Movement Disorders Centre, investigated pathological gambling, hypersexuality, and compulsive shopping in 297 patients with PD. She found that overall lifetime prevalence (which includes both past and current behaviors) for the group was 6%, which increased to 16% in patients taking levodopa and dopamine agonist in combination. The lifetime prevalence was 3.4% for pathologic gambling, 2.4% for hypersexuality, and 0.7% for compulsive shopping; 10%–20% of patients exhibited more than one disorder.

One hypothesis is that these obsessive behaviors reflect excessive stimulation of the limbic reward system in susceptible individuals. Risk factors that may increase susceptibility to compulsive behaviors include younger age of PD onset, novelty-seeking personality traits, and history of alcohol abuse. Stage of disease was ruled out as a risk factor.

These findings suggest that clinicians should regularly query patients with PD and family members about excessive behaviors, which may take the form of hobbies, collections, sexual behavior, or shopping. Early identification can help physicians make adjustments that may rectify the problematic behaviors, including switching dopaminergic agonists, discontinuing therapy if possible, or even substituting deep brain stimulation for long-term dopaminergic therapy. The latter option should be used with caution, since Suchowersky found that 5% of 39 deep brain stimulation patients actually developed pathologic gambling after surgery.

Left unchecked, serious psychosocial consequences may result from these behaviors, including isolation, shame, depression, marital discord, and suicidal thoughts. Among Dr. Voon's patients, pathologic gambling led to a mean loss of $125,000, while some of Dr. Suchowersky's patients “literally lost the farm.”