Impulsive smoking in a patient with Parkinson’s disease treated with dopamine agonists

Impulse control disorders, including pathological gambling, binge eating, compulsive shopping and hypersexual behaviors, have frequently been reported as a side effect of dopaminergic medications for Parkinson’s disease {PD (1,2,3)}, and the majority of reports have implicated dopamine agonists as a risk factor for their development (4,5,6). Recently, we evaluated a depressed 63-year-old male patient with PD who developed an unusual manifestation of impulsive behaviors, including cigarette smoking, associated with an increase in dopamine agonist medication¹.

The patient was diagnosed with PD at the age of 56 and began treatment with pramipexole two months after diagnosis. He was started on a dosage of 0.5mg TID which was gradually increased over the next few months to 1.5mg TID. He remained stable for approximately one year until he complained of significant motor symptoms and the dosage was increased to 2mg TID. Approximately one month later, the patient developed uncharacteristic obsessive and impulsive behaviors. He began smoking cigarettes, increasing to two packs per day, and reported that he could not control the urge to smoke.

His thinking also became delusional and he claimed to his family that he had been smoking for the past 30 years even though his wife reported she had never once seen him smoke during their 30-plus year relationship. The patient also developed a bizarre preoccupation with his beard. He would obsessively groom the beard and gave it a persona, stating things like “The beard is happy today” or “The beard would like his picture taken.” His wife also reported that he developed an increased preoccupation with sex and made inappropriate sexual comments to his daughter’s teenage friends, although he denied any recollection of this. He also denied any alcohol or drug use at this time.

Given the problems associated with the dosage increase, pramipexole was eventually tapered and discontinued. The abnormal behaviors disappeared and the patient reported that he no longer felt the urge to smoke. The patient then began treatment with carbidopa/levodopa, and eventually with combination carbidopa/levodopa/entacapone. However, over the next six months, the patient continued to complain of significant motor symptoms, including rigidity, tremor, and frequent wearing off. He was prescribed ropinirole and treated with varying doses over the next four years. Within one month of the ropinirole being increased to 3mg TID, the patient again developed a problem with impulsive smoking.

A few months later, his medication was switched to ropinirole XL 8mg qd due to persistent motor difficulties. The patient continued to impulsively smoke, keeping both the medication dosage changes and cigarette smoking hidden from his wife. His wife eventually discovered the smoking and sought out our group for help. She also reported that he was making increased sexual advances towards her, although a preoccupation with his beard did not re-emerge.

At the time of his initial appointment, the patient had begun 12mg of ropinirole XL and reported that his smoking was extremely hard to control, despite the difficulties it was causing in his marriage. Ropinirole was tapered and discontinued, and smoking again ceased. As of our last contact with the patient, there had been no recurrence of smoking.

The clinical phenomena noted in this case are consistent with several studies that have suggested a relationship between dopamine agonists and uncharacteristic behavioral disturbances in PD (4,5,6). In addition to factors such as early disease onset and history of depression (7,8), research has shown that PD patients with ICDs tend to be on higher daily dosages of dopamine agonists than agonist-treated PD patients without ICDs (4,5), suggesting that the relationship between impulse control dysfunction and agonists is dose dependent. Indeed, our patient’s impulse problems initially developed when pramipexole was increased. He experienced a complete resolution of these behaviors after discontinuation of the drug and they did not reemerge upon treatment with lower therapeutic doses of ropinirole. However, once ropinirole was increased, the patient experienced a recurrence of impulsive smoking.

To the best of our knowledge, this is the first account of impulsive cigarette smoking related to the use of dopamine agonists to treat PD. However, epidemiological evidence has demonstrated that individuals with PD are less likely to have a lifetime history of smoking (9). Some have suggested this phenomenon may be related to dysfunction in the mesolimbic dopaminergic system, which mediates reward and pleasure-seeking behavior, and is implicated in the rewarding effects of addictive drugs such as opiates, amphetamines and nicotine (10). Thus, for PD patients, substances such as cigarettes may be experienced as less rewarding due to damage in this system (10).

One possible explanation for the development of our patient’s smoking habit may be that higher doses of an agonist caused an overstimulation of mesolimbic dopamine receptors that mediate reward, causing smoking to be experienced as highly pleasurable. Given the negative consequences illustrated by this case, careful clinical monitoring of PD patients on agonists, particularly those with young onset and comorbid depression, is needed. Further research is warranted to examine cigarette smoking as an impulse control problem, including the role of genetics in this phenomenon (11), in PD.