Transdermal rotigotine causes impulse control disorders in patients with restless legs syndrome

Abstract

Introduction: Dopaminergic drugs are the mainstay of treatment for restless legs syndrome (RLS). We analyzed the frequency and clinical characteristics of impulse control disorders (ICD) in patients with RLS on transdermal rotigotine treatment. Methods: Retrospective case series at a university movement disorder clinic (n = 28, 17 women). Symptoms of ICD were assessed via detailed history taking and scoring with the Zurich Screening Questionnaire for ICD (ZICD) prior to and after initiation of treatment. Results: None of the patients had a history of ICD prior to treatment. Baseline mean scores for patients who did (8.0 ± 2.5) and did not (6.2 ± 2.7) develop ICD under treatment did not differ. Six male patients (21%) developed various symptoms of ICD (mean ZICD scores 20.7 ± 10.2) on rotigotine treatment (mean dose: 3.8 mg/d), including binge eating, hypersexuality, compulsive shopping, pathological gambling, and punding, equaling a prevalence rate of 21%. Also in the non-ICD group, ZICD scores increased (7.5 ± 2.8). Conclusion: This is the first report of ICD in patients treated with transdermal rotigotine for RLS. In contrast to literature, even low doses of rotigotine (mean 3.8 mg/d) can cause ICD. Therefore every prescribing physician should be aware that ICD may emerge in both RLS and PD patients on any dopaminergic treatment, and should actively ask for such symptoms. The ZICD questionnaire not only replicated the findings of detailed history taking but also showed an increased tendency towards impulsive behaviour in subjects that did not develop ICD.

Introduction

Restless leg syndrome (RLS) belongs to the most prevalent sleep-wake disorders and is defined clinically by unpleasant sensations in the legs, associated with an urge to move, worsening during rest and night, and improvement by movement [1]. Supportive diagnostic criteria include positive family history for RLS, periodic limb movements during sleep on polysomnography, and response to dopaminergic agents [1]. The standard treatment of RLS consists of dopaminergic agents including non-ergot dopamine agonists and levodopa.

In a significant portion of patients with Parkinson’s disease (PD), dopamine agonists cause a wide range of debilitating impulse control disorders (ICD) such as hypersexuality, pathological gambling, binge eating, compulsive shopping, and punding [2]. More recently, evidence emerged that ICD may also affect RLS patients on oral dopaminergic compounds including pramipexol, ropinirole, levodopa and pergolide [3], [4], [5].

Impulse control disorders have been reported in the literature to occur in 7–17% of RLS patients [6]. A retrospective questionnaire based study of 70 RLS patients reported an increased sex drive in 4 (5%) and a change in gambling behaviour in 5 subjects (7%) after the initiation of pramipexole or ropinirole [7]. One prospective study of 89 RLS patients on dopamine agonists revealed increased impulsive behaviour in 8 patients (9%) [8]. A prospective case–control series identified symptoms of ICD in 17% of 100 RLS patients treated with dopamine agonists compared to 8% in untreated RLS patients [3].

So far, however, rotigotine - a non-ergot D3/D2/D1 dopamine agonist with continuous transdermal release, which is approved for the treatment of RLS in many countries - has not been reported to cause ICD in RLS. In a small retrospective series of RLS [1] patients, however, we observed disturbing ICD on rotigotine monotherapy.