Compulsive habits in restless legs syndrome patients under dopaminergic treatment

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Abstract

Since the introduction of levodopa therapy and dopaminergic replacement therapy to abate symptoms of idiopathic Parkinson's disease, repetitive compulsive behaviors have been reported and are now considered to be drug-related response complications. As dopamine (DA) agonists are the licensed treatment in Restless Legs Syndrome (RLS), a survey was conducted to determine the extent to which patients with RLS present compulsive behaviors. The aim of this study was to investigate the relationship between DA agonists and the occurrence of motor or behavioral compulsions, stress, depression, and sleep disturbance in RLS patients. A questionnaire was mailed three times, at four-month intervals over a period of 8 months to all patients of the Quebec Memory and Motor Skills Disorders Clinic diagnosed with RLS. In addition to recording all medication information for RLS treatment, patients were assessed on the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Beck Depression Inventory-II (BDI-II), the Sleep Scale from the Medical Outcomes Study (MOS) and on a visual analog scale for current level of stress. A section pertaining to hobby, mania, and compulsion was also included. Analyses are based on 97 out of 151 patients (64.2%) with RLS who returned the three questionnaires. Twelve patients (12.4%) on stable DA agonist therapy (average dose 0.52 ± 0.59 mg Pramipexole equivalent) developed a new compulsive behavioral repertoire. Eating (3 women, 1 man), buying food or clothes (2 women, 1 man), trichotillomania (1 woman, 1 man), and gambling (1man) were among the compulsions developed under DA treatment. In addition, two women presented new tic-like phenomena. In contrast to the RLS patients without compulsive behaviors (53 treated with DA agonist; 32 untreated), those with compulsive habits reported experiencing more stress, depression and sleep problems. Patients with RLS with mood and stress states may be at greater risk of developing compulsive behaviors while receiving standard dosage DA agonist treatment. These behaviors are clearly linked to short-term satisfaction and underline the role of dopaminergic mesolimbic stimulation in the reinforcement process of rewarding behavioral sequences.

Introduction

Restless Legs Syndrome (RLS) is a sensorimotor disorder typically characterized by an uncomfortable feeling in the legs that develops into an urge to move. It can severely disrupt normal life functioning and an important clinical feature is the circadian variation of symptoms, which are worse in the evening and at night [1]. The differential diagnosis of RLS includes both movement and sleep disorders [2], [3].

Given their involvement in sensory and motor regulation, it is thought that the subcortical dopamine systems and possibly the diencephalospinal dopaminergic system [4], are the areas of primary dysfunction in RLS. This hypothesis rests on findings that low doses of levodopa provide almost complete relief from RLS symptoms. Levodopa/decarboxylase inhibitors and both ergot and non-ergot DA agonists have shown to be effective relative to placebo in double-blind studies, with medication usually administered in single doses around bedtime [5]. Consequently, DA agents are currently considered as the most adequate treatment for RLS.

Dopaminergic therapy in Parkinson's disease (PD) is associated with behavioral side effects [6]. The role of levodopa in punding, a stereotypical motor behavior in which there is an intense fascination with repetitive handling and examining of mechanical objects, had first been reported by Friedman for Parkinson's disease (PD) [7], [8]. Since then, the possible emergence of repetitive behaviors from elementary, stereotyped compulsions to complex reward oriented behaviors has often been noted — not only with levodopa [9] but also with any DA therapy in idiopathic PD [10]. More recently, Nirenberg et al.[11] described seven PD patients in whom compulsive eating developed in the context of the use of pramipexole. The stereotypical behavior remitted for five of the patients when the dose of pramipexole was lowered or discontinued, suggesting that it was a drug-related problem. Weintraub et al.[12] identified 18 out of 273 PD patients who developed an impulse control disorder (ICD; such as pathological gambling, compulsive sexual behavior or compulsive buying) under DA treatment. In a follow-up interview conducted 29 months later with 15 of their patients with ICD, the authors reported full remission or clinically significant reduction in compulsive symptomatology following the discontinuation or decreased dosage in DA agonist agents [13]. Other studies have also shown strong associations between DA agonist and pathologic gambling [14], [15], hypersexuality [14], [16], as well as compulsive shopping [17] in PD.

The prevalence of these disorders in PD has been determined as 0.7% with levodopa monotherapy and 13.5% with DA agonist [18]. A few cases of pathological gambling arising in the context of DA agonist treatment for RLS have also been reported [19], [20]. Finally, the psychosocial impact of these compulsive behaviors, often revealed by spouses, warrant careful detection and protection of the patients. In this perspective, we report the results of an 8-month follow-up survey in RLS patients in order to assess the relationship between DA agonists and the occurrence of motor or behavioral compulsions and their association with stress, depression, and sleep disturbance in RLS.

Section snippets

Participants

All outpatients with a diagnosis of RLS seen at the Quebec Memory and Motor Skills Disorders Research Clinic between October 1999 and December 2004 were initially included in the survey. Criterion of selection was idiopathic RLS only. Patients with secondary RLS associated with Parkinson's disease, type-II diabetes, renal insufficiency, systemic inflammatory conditions, or drug consumption were excluded.

The study was undertaken with the approval of the appropriate local ethics committee and in

Results

The χ2 analyses revealed no difference between the three groups on demographic and clinical characteristics (see Table 2), indicating that personal history of depression and premorbid anxiety disorder was equivalent between the three groups. A higher proportion of compulsive behaviors was observed in female patients (8 women vs. 4 men). For eight patients, abnormal behavioral display was similar to complex compulsory behaviors, with short-term rewarding properties such as buying clothes, buying

Sleep problems

ANOVAs on the MOS sub-scales showed a main effect of Group for daytime somnolence (F(2, 94) = 3.2, p = 0.045, η2 = 0.06). Further contrast analyses revealed that the two DA-treated groups differed from the untreated group (F(1, 42) = 5.05, p = 0.03, η2 = 0.11 and F(1, 83) = 4.07, p = 0.047, η2 = 0.05 for the comparisons between DA-treated patients with and without compulsions, respectively). Significant main effects of Group was also observed for the MOS sub-scales headache and short of breath concomitant

Discussion

The aim of the study was to investigate the occurrence of compulsive behaviors, sleep problems, depressive symptoms and stress level in a population of RLS patients under DA agonist treatment. The results showed that the patients with RLS who developed compulsive behaviors while receiving such treatment were more depressed, had higher levels of perceived stress and reported more sleep problems than DA-treated or -untreated patients without compulsive habits.

In the present study, 12.4% of RLS

Acknowledgement

This study was aided with a grant from the Quebec Memory and Motor Skills Disorders Research Center, Clinique Sainte-Anne, Québec, Québec, Canada. We thank Dr Claudia Trenkwalder for her advice in the write-up of this paper.

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