Increased prevalence of nocturnal smoking in restless legs syndrome (RLS)

Sleep Medicine 11 (2010) 218–220

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Brief Communication

Increased prevalence of nocturnal smoking in restless legs syndrome (RLS) F. Provini *, E. Antelmi, L. Vignatelli, A. Zaniboni, G. Naldi, G. Calandra-Buonaura, R. Vetrugno, G. Plazzi, F. Pizza, P. Montagna Department of Neurological Sciences, University of Bologna, Bologna, Italy

a r t i c l e

i n f o

Article history: Received 26 February 2009 Received in revised form 7 April 2009 Accepted 9 May 2009 Available online 12 January 2010 Keywords: Restless legs syndrome Nocturnal smoking Sleep-Related Eating Disorder Case-control studies Obsessive-compulsiveness Psychopathology

a b s t r a c t Objective: We investigated the prevalence of nocturnal smoking (NS) in patients with RLS. Methods: One hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls, randomly selected from the general population, underwent interviews for the presence of nocturnal smoking and for obsessive-compulsive traits, depression, excessive daytime sleepiness (EDS) and subjective sleep quality. Results: NS was more prevalent in RLS patients than controls (lifetime prevalence: 12% vs. 2%, P = 0.012). Patients with NS had more frequently Sleep-Related Eating Disorders (SRED) than patients without NS (83.3% vs. 26.1%, P = 0.0002). Pathological and borderline Maudsley Obsessive-Compulsive Inventory (MOCI) values as well as pathological values at the Beck Depression Inventory (BDI) increased from controls to RLS patients without NS to RLS patients with NS (P = 0.005 and P = 0.01, respectively). Conclusions: We demonstrate an increased prevalence of NS in patients with RLS, in many cases associated with increased SRED. NS may be associated with psychopathological traits in RLS and may be relevant in the management of RLS patients. Ó 2009 Elsevier B.V. All rights reserved.

1. Introduction RLS is a sensorimotor disorder with prevalence between 5% and 10% [1]. Several studies have described an association between RLS and psychiatric disturbances, especially anxiety, depression and panic disorder [2–4]. Higher scores for neuroticism have also been reported [5]. Excessive smoking qualifies as a distinct psychiatric disturbance, with affected patients displaying higher rates of anxiety and depression [6]. An increased prevalence of smoking has been noted in RLS patients [7,8]. In the course of a study on RLS and nocturnal eating disorders [9], we took the chance to investigate the eventual association of nocturnal smoking (NS) to RLS. We report the findings of this controlled study, documenting an increased prevalence of NS in RLS. 2. Materials and methods The materials and methods employed in this study were already reported in detail for topics concerning nocturnal eating disorders [9]. Briefly, 100 consecutive RLS patients, all Caucasian and all coming from the Emilia-Romagna region of Northern Italy (population about 4,000,000), attending our Sleep Centre from January 1981 * Corresponding author. Address: Department of Neurological Sciences, University of Bologna, Via Ugo Foscolo 7, 40132 Bologna, Italy. Tel.: +39 051 2092950; fax: +39 051 2092963. E-mail address: [email protected] (F. Provini). 1389-9457/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2009.05.016

to May 2007 and satisfying all of the four diagnostic criteria for RLS of the ICSD [1], were matched for age (±3 years), sex and town of origin to 100 normal controls, randomly selected from each town Anagraphic Register. Patients and controls were investigated by means of telephone interviews. A first investigator interviewed for demographic, habit and general clinical features and for the presence of RLS [1] and RLS severity using the International Restless Legs Rating Scale (IRLS) [10]. A second investigator, kept blind to the results of the previous interview and to the condition of either RLS patient or control, investigated the presence of daytime and nocturnal smoking and psychopathological obsessive-compulsive traits, applying the MOCI [11], and the presence of mood depression, applying the BDI [12]. Nocturnal smoking was assessed by means of a Smoking Disorder Questionnaire appropriately generated and investigating the presence (current [last 3 months] or lifetime) of NS and the frequency of the NS episodes. The questionnaire was constructed alongside the seven items of the International Criteria for the diagnosis of SRED [1] (Table I in online Supplementary material). Additionally, sleep characteristics were analysed and EDS investigated by means of the Epworth Sleepiness Scale (ESS). The study was approved by the local Ethical Committee.

3. Results RLS patients and controls did not differ in demographic characteristics and habit and general clinical features, except for the

F. Provini et al. / Sleep Medicine 11 (2010) 218–220

use of medications for concomitant diseases (i.e., RLS therapy excepted) that were significantly higher in the RLS group (72% vs. 54%, P = 0.013), even in the absence of significant differences in concomitant diseases. RLS patients had lower sleep quality and more pathological levels of EDS. RLS patients also had higher pathological and borderline scores at the MOCI than normal controls (24% vs. 10%, P = 0.030; Table II in online Supplementary material). Twelve RLS patients scored positive for NS compared to two normal controls (life prevalence), a significant difference (P = 0.012), resulting in Odds Ratio (OR) for NS of 6.7 (95% Confidence Interval [CI] = 1.4–30.7). Four out of the 12 RLS nocturnal smokers patients (vs. one control) reported cessation of NS in the last 3 months, giving a current prevalence of 8 versus 1% in the control group (P = 0.035; OR = 8.6; 95% CI = 1.1–70.8). All patients that reported cessation of NS were on therapy for RLS, compared to 5/8 of those with NS persisting in the last 3 months. The 5 patients with persisting NS as well as those with remitted NS all took dopamine agonists as therapy for RLS symptoms. Daytime smoking was not significantly increased in the RLS patients compared to the controls (19% vs. 18%, P = 1.00). Comparison of RLS patients with and without NS (Table 1) did not disclose any significant difference in demographic, habit and general clinical features, or in the sleep characteristics and ESS scores. The prevalence of current daytime smoking, however, was significantly higher among the RLS nocturnal smokers (83.3% vs. 10.2%, P < 0.0001) even though RLS patients with NS could not be classified as heavy smokers (the number of ciga-

Table 1 Characteristics of the RLS patients with NS compared to RLS without NS. P*

RLS with NS

RLS without NS

Percentage of patients

12%

88%

Men Women Body mass index mean ± S.D.

33.4% 66.6% 27.8 ± 8.4

35.2% 64.8% 26.1 ± 4.4

0.85

Daytime smokers Alcohol drinkers Coffee drinkers

83.3% 41.7% 100%

10.2% 64.8% 76%

<0.0001 0.20 0.06

Concomitant diseases: Systemic hypertension Cardio-vascular diseases Neuropsychiatric diseases Endocrinal diseases

91.7% 50% 41.7% 41.7%

71.6% 36.4% 6.8% 23.9% 18.9%

0.50 0.36 1.00 0.29 0.12

Medications for concomitant diseases (except RLS)

83.3%

69.3%

0.50

Familiarity for RLS Therapy for RLS (actual) Therapy for RLS (in the past) IRLS mean score

66.7% 75% 45.5% 19.6

52.3% 62% 37.5% 13.4

0.54 0.53 0.74 0.05

Sleep onset impairment Nocturnal awakenings (>2/night) Pathological ESS

66.7% 100% 16.7%

47.7% 93.2% 14.8%

0.36 1.00 1.00

SRED

83.3%

26.1%

MOCI Pathological values Borderline values

25% 8.3%

5.7% 17%

BDI Pathological values

58.3%

25%

1.00

0.0002 0.086

0.036

IRLS: International Restless Legs Rating Scale; Daytime smokers: current smokers (range: 1–20 cigarettes/day); Alcohol drinkers: 20–30 cc alcohol/die; Coffee drinkers: 1–2 cups/die; SRED: Sleep-Related Eating Disorder; MOCI: Maudsley Obsessive-Compulsive Inventory; BDI: Beck Depression Inventory; ESS: Epworth Sleepiness Scale. * Fisher’s Exact Test for dichotomous data; Mann–Whitney U test for continuous data.

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rettes/daily was in the range from 2 to 20, mean value 11.2 cigarettes/day, i.e., light to moderate smoking [13]). The characteristics of RLS (familiarity and presence of treatment for RLS included) did not differ significantly between nocturnal and nonnocturnal smokers, even though RLS patients with NS had a borderline increased severity of RLS at the IRLS (19.6 vs. 13.4 [mean values], P = 0.05). NS was significantly associated with nocturnal eating disorders (83.3% of RLS nocturnal smokers vs. 26.1% of RLS nonnocturnal smokers qualified for the diagnostic criteria of SRED; P = 0.0002); RLS nocturnal smokers also displayed increased BDI scores compared to RLS nonnocturnal smokers (58.3% vs. 25%, P = 0.036), whereas MOCI scores remained comparable. Nevertheless, the MOCI pathological and borderline values increased significantly from controls to RLS patients without NS to RLS patients with NS (10% vs. 22.7% vs. 33.3%, respectively, P = 0.005; Fisher’s Exact Test), as well as the BDI pathological values (19% vs. 25% vs. 58.3%, respectively, P = 0.010; Fisher’s Exact Test). The clinical characteristics of RLS nocturnal smokers are shown in Table III (online Supplementary material). Patients described how they woke up in the night with a distinct craving for smoking, which they could not easily resist, and how they could not return to sleep without having smoked. Mean age of NS onset was reported at 47.8 years, while mean RLS onset was reported at 42 years. In 3 patients RLS and NS arose simultaneously, in 2 NS before RLS (by 12 and 17 years), and in 7 patients RLS began 1–45 (mean 14) years before NS. NS and nocturnal eating usually began simultaneously, except in 2 patients in whom NS preceded nocturnal eating by 5 and 13 years. Almost all patients reported one or 2, and 2 patients reported 3– 5 episodes per night; episodes usually occurred soon after sleep onset and rarely in the middle of the night. The positive answers to the seven questionnaire items for NS are reported in Table I (online Supplementary material).

4. Discussion This study demonstrated an increased prevalence of current and lifetime NS in patients affected with RLS and referred to a Sleep Centre for diagnosis and treatment. It represents a companion study of the one investigating the presence of nocturnal eating disorders in RLS [9]. This was a controlled study, in which an age-, sex- and ethnicity-matched control population was obtained randomly from the Anagraphic Registers of each town of provenance for every RLS patient. We adopted a design in this study, whereby the clinician interviewing for NS was kept blind to the results of a previous interview for RLS presence and characteristics. We must, however, acknowledge that ours is a tertiary care study, and therefore our findings may apply only to these selected referral patients and not to the general RLS population. Moreover, our RLS patients could be on medications for RLS, and therefore any inference to the effects of therapy and its pathogenic implications on NS is not warranted. These limitations notwithstanding, RLS patients came out as having significantly higher rates of nocturnal smoking. We had already observed NS as a behaviour associated with some sleep disorders [14]. These findings raise some interesting pathophysiological questions. Nocturnal sleep-disturbing nicotine craving was previously attributed to extreme nicotine dependence [15] because of dwindling nicotine levels in the blood [16]. In these studies, however, patients were extreme nicotine addicts and also heavy daytime smokers (more than 20 cigarettes daily), and the eventual presence of RLS was not investigated. Extreme craving and the pharmacokinetics of nicotine blood levels may in part explain the nocturnal smoking habit that we detected in our RLS patients. Nevertheless

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we must note that, first, the RLS nocturnal smokers were only mild or moderate smokers (in the range of 2–20 cigarettes daily); second, there was no higher prevalence of daytime smoking in the RLS population, only NS being significantly increased; third, NS was significantly associated with nocturnal eating disorder in our RLS patients. Incidentally, nicotine has some dopamine-stimulating effects [17], and it could be that nicotine intake during the night could ease the symptoms and signs of RLS. As an explanation, we suggest that NS in RLS represents compulsive habit behaviour possibly facilitated by the nocturnal arousals characteristic of RLS. We found that pathological obsessive-compulsive scores were in fact increased in RLS patients with NS, as were the BDI depression scores. As an alternative explanation we cannot exclude that NS represents merely a mean to kill time in the attempt to recapture sleep, since sleep fragmentation and wakefulness during the night are more likely to occur in RLS patients than in controls. Such an explanation has also been put forward for the association of SRED to RLS [9] and should be tested with comparison to other sleep pathologies with increased wakefulness after sleep onset, such as insomnia. We acknowledge the lack of insomnia controls in the study, and therefore the nature of the association remains investigational. Nonetheless, we suggest that our findings of increased NS may become relevant in the management of patients given the adverse effects of smoking on health and the possible association of RLS to hypertension and cardio-vascular disease [3,18]; they also imply that the psychopathological, especially obsessive-compulsive traits, should be investigated more deeply in RLS.

Acknowledgements Ms. A. Laffi helped with the manuscript preparation. Supported by 2007 RFO University of Bologna grants (to F.P. and P.M.).

Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.sleep.2009.05.016.

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