Sleepiness and driving performance in adults with Attention Deficit Hyperactivity Disorder (ADHD)

Abstracts / Sleep Medicine 14S (2013) e18–e92

K, Tsujimoto S, Samma S. ‘‘Endocrine response to a single injection of goserelin 3.6 mg or leuprolide 3.75 mg in men with prostate cancer. Arch Androl. 2007 Mar-Apr;53(2):87-90. 3. Ferrari B, Pezzuto A, Coppola F. ‘‘Massive ascites and hydrothorax after leuprolide acetate administration in a down-regulated woman undergoing assisted reproduction’’. Fertil Steril. 2007 Oct;88(4):968.e9-11. Epub 2007 Apr 16. 4. Lodde M, Lacombe L, Fradet Y. ‘‘Salvage therapy with bicalutamide 150 mg in non metastatic castration-resistant prostate cancer’’. Urology. 2010 Nov;76(5):1189-93. Epub 2010 Mar 29. 5. Akaza H. ‘‘Combined androgen blockade for prostate cancer: review of efficacy, safety and cost-effectiveness’’. Cancer Sci. 2011 Jan;102(1):516. doi: 10.1111/j.1349-7006.2010.01774.x. Epub 2010 Nov 22. Review. 6. Labrie F. ‘‘Hormonal therapy of prostate cancer’’. Prog Brain Res. 2010;182:321-41. http://dx.doi.org/10.1016/j.sleep.2013.11.144

Sleep in restless legs syndrome improves during opioid treatment – Results from a large 1-year multi-center trial H. Benes 1, C. Trenkwalder 2, D. Garcia-Borreguero 3, B. Bosse 4, M. Hopp 4, R. Kohnen 5 1 Somni bene Institute for Clinical Research and Sleep Medicine, Germany 2 Paracelsus-Elena Hospital, Centre of Parkinsonism and Movement Disorders, Germany 3 Sleep Research Institute, Germany 4 Mundipharma Research GmbH&Co. KG, Germany 5 ReSearch Pharmaceutical Services Inc., Germany

Introduction: In severe cases of restless legs syndrome (RLS), symptoms result in bothersome impact on sleep and impairment of daytime function. This study showed superior efficacy of oxycodone/naloxone prolonged-release fixed-combination (OXNPR) vs. placebo for the primary endpoint (International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score) in severely affected RLS patients. The impact of RLS on sleep quality was assessed as a secondary endpoint. Materials and methods: After screening and a 7-day washout, 304 patients (age 62¡À11.2 years) with failed prior RLS therapy and an IRLS score ¡Y´21 were randomized to double- blind OXNPR bid (mean oxycodone dose 21.9¡À15.0 mg/day) or placebo for 12 weeks. 197 patients participated in a 40-week open-label extension (mean oxycodone dose 18.1¡À10.5 mg/day). Sleep was subjectively assessed by the Medical Outcomes Study (MOS) sleep scale, by item 4 of the IRLS (sleep disturbance due to RLS symptoms) and 4 questions of the RLS6: Q1 (sleep satisfaction), Q2/3 (RLS symptom severity at falling asleep/during the night), and Q6 (daytime tiredness). Results: MOS sleep scale results showed greater improvement in sleep quality for OXNPR vs. placebo; OXNPR-treated patients fell asleep more quickly, slept for longer, experienced less sleep disturbance and greater sleep adequacy than placebo- treated patients (p < 0.001). The IRLS¨C item 4 showed that sleep disturbance was ’very severe’ at baseline (median = 4 on a scale of 0–4) but had improved to ’mild’ (median = 1) in the OXNPR group and severe (median = 3) in the placebo group at Week 12. These results support results for IRLS total score. The RLS-6 was scored on a 0–10 scale; higher values represent more severe symptoms. Patients were highly dissatisfied with sleep at baseline (score of 8.2¡À2.0 for Q1), but improved with a score of 3.8¡À3.1 for OXNPR at Week 12. Similarly, results for Q2 improved from 7.2¡À2.6 to 2.7¡À2.9, results for Q3 improved from 7.5¡À2.4 to 2.8¡À3.0 and results for Q6 improved from 6.4¡À2.8 to 3.7¡À3.0. The improvement was significantly larger for OXNPR than placebo (p < 0.001).

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Conclusion: In this analysis of an important secondary outcome measure, we demonstrated that treatment with OXNPR improves sleep quality in the context of an overall favorable treatment effect in severely affected RLS patients who failed on previous RLS medications. Acknowledgements: Karen Paine provided medical writing services on behalf of Mundipharma Research. (Funded by Mundipharma Research; ClinicalTrials.gov number, NCT01112644). http://dx.doi.org/10.1016/j.sleep.2013.11.145

The effect on sleep inertia on pain perception depends on the type of pain D. Benjamin, R. Inkley, A. Bentley Brain Function Research Group, Faculty of Health Sciences, South Africa

Introduction: The impact of sleep inertia on cognitive performance has been well documented. There is a delay in full function which is worse when woken from slow wave sleep and may last for up to 60 min. The impact of this inertia on the perception of pain has been under-researched although some hypoalgesia with heat pain after waking from REM sleep has been documented. The objective of this research was to see the effect of sleep inertia on the perception of two different pain modalities. Materials and methods: Eleven healthy male subjects aged 19–28 were brought into the sleep lab on three occasions. On each occasion pressure pain thresholds as well as a range of temperature (heat) pain stimuli were applied to the lateral thigh area twice 15 min apart while awake. Standard polysomnographic channels were recorded and subjects were woken during stage 2, slow wave sleep and REM sleep. After waking both pressure pain threshold and heat pain (measured by temperature and severity of pain measured by visual analogue scales) were repeated both 30 s and 15 min after waking. Results: There were significant differences in the temperature data measured 15 min apart during waking but not in pressure pain thresholds. When compared to awake data the pressure pain thresholdswere significantly lower measured at both 30 s (p = 0.001) and 15 min (p = 0.001) after waking from stage II. There was evidence of hypoalgesia after forced waking from SWS. Conclusion: After forced waking from sleep there is consistent hyperalgesia for pressure pain thresholds which lasts for at least 15 min after waking. There is isolated hypoalgesia for increased temperatures after slow wave sleep only. While hypoalgesia may be explained by sleep inertia it is unclear how to explain excessive sensitivity to pressure pain. Acknowledgements: Funding obtained from Wits Dial.a.Bed Sleep Laboratory. http://dx.doi.org/10.1016/j.sleep.2013.11.146

Sleepiness and driving performance in adults with Attention Deficit Hyperactivity Disorder (ADHD) S. Bioulac 1, A. Capelli 2, A. Claret 3, J. Taillard 2, M. Bouvard 3, P. Philip 4 1 Child and Adolescent University Psychiatry, USR CNRS 3413, United States 2 USR CNRS 3413, United States 3 Child and Adolescent University Psychiatry, United States 4 USR CNRS, United States

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Abstracts / Sleep Medicine 14S (2013) e18–e92

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by a triad of symptoms involving hyperactivity, impulsivity and inattention. Several studies in children with ADHD showed a high prevalence of excessive daytime sleepiness. To our knowledge, no study has objectively assessed sleepiness in adults with ADHD. Moreover, it has been shown that adults with ADHD were at risk for driving accidents. The objectives of this study are to quantify objective sleepiness and its impact on driving performance in adult with ADHD. Materials and methods: 36 subjects with ADHD (age (mean  SE) = 36.3  1.6) and 18 control subjects (age (mean  SE) = 31.2  1.2) were included. Nocturnal polysomnography was performed to identify potential sleep disorder. The next day patients were submitted to a Maintenance Wakefulness Test (MWT) at 10H, 12H, 14H, 16H to examine their level of daytime sleepiness. After a training of 15 min, a driving test of 1 h was carried out at 17H on a simulator (Oktal) to evaluate driving performance. Results: ADHD subjects were divided into 2 groups according to their level of sleepiness at the MWT: the ’’sleepy’’ group consisted of twenty subjects (mean sleep latency (SL) = 23.9  1.3 min) and the ‘‘alert’’ group included sixteen subjects (LE = 37.3  1 min)(p = 0.001). We observed that more than half of the ADHD subjects exhibit a sleep disorder: 31% among the alert ADHD subjects and 65% among sleepy ADHD subjects. But 35% of the sleepy ADHD subjects did not presented a sleep disorder. About driving performance, there were significant differences between driving performance (observed by the number of lines crossing) between the control group and the alert ADHD group (p = 0.05) and the control group and the sleepy ADHD group (p = 0.02). Conclusion: This study supports the hypothesis that there is a sub group of ADHD patients that present pathological sleepiness. In our sample, half of the patients suffer of excessive daytime sleepiness. But it is appropriate to question the origin of the sleepiness found in the other patients and to wonder if they represent a particular phenotype. ADHD impacts on driving performances, but it is not possible today to clearly explain them: attention deficit and/or sleepiness? But it is important to focus on this question to provide therapeutic strategy modulated by the clinic. Acknowledgements: JP rénéric. http://dx.doi.org/10.1016/j.sleep.2013.11.147

Symptoms of insomnia among OSA patients before and after 2 years of PAP treatment E. Bjornsdottir 1, C. Janson 2, E. Arnardóttir 1, A. Pack 3, T. Gislason 1, B. Benediktsdottir 1 1 Faculty of Medicine, University of Iceland, Iceland 2 Uppsala University, Sweden 3 Center for Sleep and Circadian Neurobiology, Division of Sleep Medicine, Department of Medicine, United States

Introduction: To assess the changes of insomnia symptoms among patients with obstructive sleep apnea (OSA) from starting treatment with positive airway pressure (PAP) to a two-year follow-up. Materials and methods: All subjects underwent a medical examination, type 3 sleep study and answered questionnaires on health and sleep before and 2 years after starting PAP treatment. The change in prevalence of insomnia symptoms by subtype were assessed by questionnaire and compared between individuals who were using or not using PAP at follow-up. Results: Symptoms of middle insomnia were most common at baseline and improved significantly among subjects using PAP (from 59.4% to 30.7%, p < 0.001). Symptoms of initial insomnia tended to

persist, regardless of PAP treatment and symptoms of late insomnia were more likely to improve among subjects not using PAP. Subjects with symptoms of initial and late insomnia at baseline were less likely to adhere with PAP (odds ratio (OR) 0.56, p = 0.007, and OR 0.53, p < 0.001, respectively). Conclusion: PAP treatment significantly reduced symptoms of middle insomnia. Symptoms of initial and late insomnia, however, tended to persist regardless of PAP treatment and had a negative effect on treatment adherence. Targeted treatment for insomnia may be beneficial for patients with OSA comorbid with insomnia and has the potential to positively affect adherence to PAP. Acknowledgements: Support: NIH grant HL72067 for ‘‘A Family Linkage Study of Obstructive Sleep Apnoea’’ and HL94307 for ‘‘Endophenotypes of Sleep Apnea and Role of Obesity’’, the Eimskip Fund of the University of Iceland and the Landspitali University Hospital Research Fund. http://dx.doi.org/10.1016/j.sleep.2013.11.148

A randomized controlled trial of the effects of bright light and melatonin for delayed sleep phase disorder B. Bjorvatn 1, I. Saxvig 1, A. Wilhelmsen-Langeland 1, Ø. Vedaa 2, I. Nordhus 1, S. Pallesen 1 1 Haukeland University Hospital, Norwegian Competence Center for Sleep Disorders, Norway 2 University of Bergen, Department of Psychosocial Science, Norway

Introduction: Delayed sleep phase disorder (DSPD) is a circadian rhythm sleep disorder. Patients with DSPD have problems initiating sleep if they go to bed at a conventional time and they have serious problems waking at desired times. In the present study we investigated short- and long-term effects of timed bright light and exogenous melatonin treatment alongside gradually advanced rise times in adolescents/young adults with DSPD in a randomized controlled two- week trial with an open label 3-month follow-up study. Materials and methods: Forty patients (16–25 years) diagnosed with DSPD were recruited to participate. The participants were randomized to receive treatment for 2 weeks in one of four treatment conditions: dim light + placebo capsules, bright light + placebo capsules, dim light + melatonin capsules or bright light + melatonin capsules. In the follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep and daytime function as assessed by sleep diaries, actigraphy, sleepiness/fatigue recordings, cognitive function and circadian phase (assessed by salivary dim light melatonin onset (DLMO)). Results: During the two-week intervention, the timing of sleep and DLMO were advanced in all treatment conditions with no interaction effects (two-way ANOVA); about one hour advance of bed time, 2 h advance of rise time and two hours advance of DLMO in all four groups. Sleep duration was reduced with one hour. Subjective sleepiness, fatigue and cognitive function also improved significantly after two weeks of treatment, again with no interaction effects. At threemonth follow-up, the no-treatment group had returned to baseline on all measures, whereas the treatment group had maintained an advanced sleep phase as well as improved scores on sleepiness, fatigue, and cognitive function. Sleep duration had increased. Conclusion: Gradual advancement of rise time produced a phase advance and an improved daytime function during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times and poor daytime