Drug Dosage, Gender Affect Impulsivity Prognosis in Parkinson's

The development and resolution of impulse control disorders in patients with Parkinson’s disease appears to be largely reliant on gender, daily dose of dopamine agonists, and the presence of depressive symptoms, according to a prospective study.

Persistence of impulse control disorders (ICDs) among Parkinson’s disease patients from baseline to a mean follow-up of about 15 months were significantly associated with male gender and a higher daily dose of dopamine agonists. However, worsening depressive symptoms was the only factor associated with the development of an ICD during follow-up, reported Dr. Juho Joutsa of the University of Turku (Finland) and his colleagues (Parkinsonism Relat. Disord. 2012 [doi:10.1016/j.parkreldis.2012.06.005]). Their study is the first large-scale, prospective study to assess risk factors for the development and resolution of ICDs at two time points.

The investigators used self-reports from 290 survey participants who had had Parkinson’s disease for a median of 6 years and were a median age of 64 years at baseline. Among 270 patients who answered questions about ICDs on the Questionnaire for Impulsive-Compulsive Behaviors in Parkinson's Disease at both baseline and follow-up, 22 had a new-onset ICD at follow-up, 31 had their ICDs resolve at follow-up, 135 had no ICD at both baseline and follow-up, and 82 reported stable ICDs at both time points.

In the patients with ICDs at baseline, multivariate binary logistic regression analyses showed significantly higher odds for the presence of ICDs at follow-up if the patient was a man (odds ratio, 6.10).

"The present results demonstrate that ICDs are not only more common in men but also approximately six times more unlikely to be resolved, compared to women during a 15-month follow-up. Thus, the results also suggest that the difference in prevalence rates between the sexes found in cross-sectional studies should not be interpreted only as higher incidence of ICDs in men. However, future studies are required to clarify whether ICDs in male patients are more treatment resistant or if men are more reluctant to seek treatment for ICDs," the investigators wrote.

The multivariate analysis also found significantly higher odds for the presence of ICDs at follow-up among patients who had a higher dopamine agonist levodopa-equivalent daily dose at baseline (OR 2.25 for every 100-mg increase). However, the effect of dopamine agonist dose did not differ between genders.

"Although the baseline dopamine agonist dose was associated with ICD outcome, we did not observe significant effect of the change in the agonist dose," Dr. Joutsa and his associates wrote.

The investigators found that the optimal levodopa equivalent daily dose cut off at baseline for predicting a poor ICD outcome was 161 mg or greater, resulting in a 46% sensitivity, 90% specificity, 93% positive predictive value, and 37% negative predictive value. That level of levodopa equivalent daily dose, which corresponds to 1.6 mg pramipexole and 8 mg ropinirole, "is quite low compared to the maximal doses of the drugs, and to the doses needed for efficacious motor symptom treatment. The relatively low cut-off values suggest that ICDs are associated with dopamine agonists even with low daily doses, when the first motor benefit is reached," they wrote.

A rise in score on the Beck Depression Inventory (BDI) proved to be the only significant predictor of ICDs at follow-up among patients without ICDs at baseline, increasing the odds of developing an ICD by nearly 10% for each 1-point increase on the scale. Those who developed new-onset ICDs at follow-up had a mean BDI score of 8.4 at baseline and 12 at follow-up. Overall, patients with ICDs at either time point had a higher mean BDI score than did those without ICDs, with baseline scores of 14.2 vs. 8.9, respectively, and follow-up scores of 12.9 vs. 9.8.

However, patients who had resolved their ICDs at follow-up did not improve their depressive symptoms to the level seen in patients who never had ICDs, showing that "depressive symptoms at baseline did not predict the ICD outcome at follow-up," Dr. Joutsa and his colleagues wrote. "Therefore, these results could be interpreted to favor ICDs as a causal factor for depression rather than vice versa, although the design of the study does not allow definitive conclusions about the causality."

The research was funded by the Finnish Alcohol Research Foundation, the Finnish Medical Foundation, the Turku University Hospital, the Turku University Foundation, the Paulo Foundation, and the Finnish Parkinson Foundation. All but one of the authors declared having financial relationships with Boehringer-Ingelheim, GlaxoSmithKline, UCB Pharma, and Orion Pharma, Abbott, and Lundbeck.