New-onset impulse control disorders after treatment with levodopa–carbidopa intestinal gel in Parkinson's disease

Dear Editor:

Impulse control disorders (ICDs), are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of patients.¹ ICDs have been mostly related to the use of dopamine agonists (DAs). However, ICDs have also been reported to occur with levodopa, monoamine oxidase inhibitors, and amantadine treatment, as well after deep brain stimulation.^1,2

Levodopa treatment has been associated with compulsive behaviors such as punding and dopaminergic dysregulation syndrome.^3,4

Levodopa–carbidopa intestinal gel (LCIG) is a treatment that has been reported to be beneficial in patients with advanced Parkinson's disease. LCIG treatment can reduce OFF periods and improve motor as well as non-motor symptoms.^5,6

Switching patients with advanced PD from oral medications to LCIG has been reported to improve IDCs. More stable plasma levels of levodopa and discontinuation of dopamine agonist are thought to underlie the improvement.²

We here report our experience regarding two patients with advanced Parkinson's disease who developed a de novo ICD with LCIG.

Case 1. A 70-year-old male with advanced Parkinson's disease that had started ten years ago and that was complicated with motor fluctuations. Treatment with LCIG was initiated, resulting in a reduction in OFF periods of >50%. The initial dose of levodopa was 1340 mg per day (before LCIG the equivalent dose of levodopa was 1500 mg/day). No extra doses were administered and no other concomitant oral medication was necessary. After a month, the patient developed hypersexuality that manifested as an increased sex drive. They had not exhibited this abnormal behavior previously. Initially, quetiapine up to 100 mg/day was added. In later weeks, it became necessary to reduce the levodopa doses. As the patient experienced motor deterioration, the total dose of levodopa was increased again to 1400 mg/day, which resulted in continued hypersexuality. Ultimately, the LICG was withdrawn two years later because the patient developed cognitive impairment.

Case 2. A 58-year-old patient who for the past 12 years had suffered from Parkinson's disease that was complicated with wearing off-type motor fluctuations with more than 15 h of OFF periods. Before LCIG, the equivalent dose of levodopa was 1200 mg/day. LCIG treatment was started and resulted in a good motor response. The initial dose of levodopa was 1246 mg/day and pramipexole was maintained at 0.52 mg/day. One month later, the pramipexole was withdrawn due to choreic dyskinesias. Six months later, the patient developed a pathological gambling behavior and hypersexuality: he started playing Bingo and visiting brothels on a daily basis. Initially, the daily dose of levodopa was reduced. However, as this resulted in motor deterioration, quetiapine was added. At present, after five years of LCIG treatment, the patient still suffer from ICD and finally was institutionalized.

There is experience in the literature of new-onset ICDs after the initiation of LCIG.⁷ The ICDs in our cases arose with levodopa monotherapy (>1000 mg in both cases) and with no personal history of previous ICDs. Reductions in the levodopa doses were not possible and quetiapine could only partially control the ICDs.

The high doses of levodopa achieved with LCIG do not fully explain the occurrence of ICDs. It is possible that a personal susceptibility promotes the development of such behaviors, and prospective studies are needed to investigate whether there may be an increased risk of ICDs with LCIG treatment.

Funding

The authors declare that there is no financial support or competing interests regarding this manuscript.

The authors state that the current manuscript has not been presented at a professional meeting. Patient consent was obtained for publication of the case report.

Author contributions

ACC, GVA and MMS have collected the data and written the draft of the manuscript. FGP has reviewed and approved the manuscript. All authors approved the final draft for submission. FGP is the article guarantor.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements

None.