- Email: [email protected]
Modafinil for the treatment of excessive daytime sleepiness in Parkinson's disease: a case report
Parkinsonism & Related Disorders Parkinsonism and Related Disorders 7 (2001) 287±288
www.elsevier.com/locate/parkreldis
Case report
Moda®nil for the treatment of excessive daytime sleepiness in Parkinson's disease: a case report A. Rabinstein, L.M. Shulman, W.J. Weiner* Department of Neurology, University of Miami School of Medicine, 1501 NW 9 Avenue, Miami, FL 33136, USA Received 2 June 2000; accepted 2 June 2000
Abstract We report a 59 year old woman with levodopa responsive Parkinson's disease who developed excessive daytime sleepiness [Epworth Sleepiness Scale (ESS) score of 13]. Treatment with Moda®nil 400 mg daily within two weeks produced a subjective improvement in her daytime sleepiness (ESS score after treatment is 8) with no signi®cant change in her PD motor symptomotology. q 2001 Elsevier Science Ltd. All rights reserved. Keywords: Moda®nil; Excessive daytime sleepiness; Parkinson's disease
Sleep disorders occur frequently in patients with idiopathic Parkinson's Disease (PD), adversely affecting their quality of life [1]. Impaired nocturnal sleep, with multiple prolonged awakenings may lead to daytime sleepiness even in early stages of the disease. Moda®nil is a non-amphetamine stimulant recently approved by the US Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy [2]. We report a patient with PD and EDS who was successfully treated with moda®nil. Case Report: A 59-year-old woman with idiopathic PD (Hoehn and Yahr stage 2) complained of (EDS) for the last 3 months. She was initially diagnosed with PD three years ago when she developed a resting tremor of her right hand and slowing of motor functions including handwriting changes and loss of ®nger and hand dexterity. Since the onset of symptoms there has been a mild progression. In the previous year depression and anxiety had complicated her PD but this had responded well to sertraline. On examination, her mental function was normal and her mood was not depressed. She was alert, cooperative and there was no evidence of somnolence or memory dysfunction. Her motor examination showed mild to moderate bilateral cogwheel rigidity in the upper extremeties and moderate bilateral slowing of ®nger and hand movements. She had no tremor or dyskinesias. Her gait and balance were excellent. Her medications included carbidopa/levodopa 25/100 mg TID, amantadine 100 mg BID and sertraline 100 mg daily. She * Corresponding author. Tel: 11-305-243-6332; fax: 11-305-243-4678.
scored 13 on the Epworth Sleepiness Scale (ESS) [3] indicating she had signi®cant daytime sleepiness. Moda®nil 200 mg qAM was initiated for one week and increased to 400 mg qAM. Within 2 weeks she reported improvement in EDS. On return to the movement disorder clinic three months later the patient reported considerable subjective improvement in her EDS and her ESS score had dropped to 8 (nonsigni®cant EDS). She reported a mild increase in tremor in her right hand but no important functional change in her motor status. There were no adverse events associated with moda®nil use. On repeat examination her motor ®ndings were stable and unchanged. Sleep disturbance in PD ranges from nocturnal vocalizations, vivid nightmares, REM sleep disorder to marked failure to initiate sleep and sleep fragmentation. EDS is quite prevalent and often represents a very signi®cant problem in the management of PD. The ef®cacy of moda®nil in the treatment of EDS has been reported in narcolepsy [4,5]. Although the mechanism of action of this drug effect is not yet established preclinical data has been published suggesting that it may ameliorate both MPTP induced dopaminergic cell damage in the mouse and glutamate induced cytotoxicity in cultured cortical neurons [6]. Either of these potential effects makes the compound of increased interest in PD. Moda®nil does not seem to affect the extrapyramidal motor system as do other psychostimulants such as amphetamine [7] and this combined with its lower potential for dependency and abuse [2], make it a possible option for the treatment of EDS in PD patients. Although not listed as an
1353-8020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S 1353-802 0(00)00035-3
288
A. Rabinstein et al. / Parkinsonism and Related Disorders 7 (2001) 287±288
adverse event in the pivotal studies of moda®nil in narcolepsy, the package insert states that occasional elderly patients developed oro-facial dyskinesias [4,5]. This may prove to be a troublesome adverse event in patients with PD. Our patient did not develop any dyskinesia when moda®nil was added to her carbidopa/levodopa, amantadine and sertraline. It is unlikely that sertraline was responsible for the EDS since the patient had been taking it for nine months with no reported somnolence. Even if sertraline was contributing to her EDS it is still noteworthy that moda®nil relieved her symptoms. We report the successful treatment of EDS in PD with moda®nil. We believe that further studies should be undertaken in order to de®ne the potential role of moda®nil in the management of patients with PD. Acknowledgements This work supported in part by The Rosalyn Newman Foundation and The National Parkinson Foundation.
References [1] Karslen KH, Larsen JP, Tandberg E, Mealand JG. In¯uence of clinical and demographic variables on quality of life in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1999;66(4):431±5. [2] Anonymous. Moda®nil for narcolepsy. Med Lett Drugs Ther 1999;41(1049):30±1. [3] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14(6):540±5. [4] Laffont F, Mayer G, Minz M. Moda®nil in diurnal sleepiness. A study of 123 patients. Sleep 1994;17(8):S113±5. [5] US Moda®nil in Narcolepsy Multicenter Study Group. Randomized trial of moda®nil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998;43(1):88±97. [6] Antonelli T, Ferraro L, Hillion J, Tomasini MC, Rambert FA, Fuxe K. Moda®nil prevents glutamate cytotoxicity in cultured cortical neurons. Neuroreport 1998;9(18):4209±13. [7] Engber TM, Dennis SA, Jones BE, Miller MS, Contreras PC. Brain regional substrates for the actions of the novel wake-promoting agent moda®nil in the rat: comparison with amphetamine. Neuroscience 1998;87(4):905±11.
www.elsevier.com/locate/parkreldis
Case report
Moda®nil for the treatment of excessive daytime sleepiness in Parkinson's disease: a case report A. Rabinstein, L.M. Shulman, W.J. Weiner* Department of Neurology, University of Miami School of Medicine, 1501 NW 9 Avenue, Miami, FL 33136, USA Received 2 June 2000; accepted 2 June 2000
Abstract We report a 59 year old woman with levodopa responsive Parkinson's disease who developed excessive daytime sleepiness [Epworth Sleepiness Scale (ESS) score of 13]. Treatment with Moda®nil 400 mg daily within two weeks produced a subjective improvement in her daytime sleepiness (ESS score after treatment is 8) with no signi®cant change in her PD motor symptomotology. q 2001 Elsevier Science Ltd. All rights reserved. Keywords: Moda®nil; Excessive daytime sleepiness; Parkinson's disease
Sleep disorders occur frequently in patients with idiopathic Parkinson's Disease (PD), adversely affecting their quality of life [1]. Impaired nocturnal sleep, with multiple prolonged awakenings may lead to daytime sleepiness even in early stages of the disease. Moda®nil is a non-amphetamine stimulant recently approved by the US Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy [2]. We report a patient with PD and EDS who was successfully treated with moda®nil. Case Report: A 59-year-old woman with idiopathic PD (Hoehn and Yahr stage 2) complained of (EDS) for the last 3 months. She was initially diagnosed with PD three years ago when she developed a resting tremor of her right hand and slowing of motor functions including handwriting changes and loss of ®nger and hand dexterity. Since the onset of symptoms there has been a mild progression. In the previous year depression and anxiety had complicated her PD but this had responded well to sertraline. On examination, her mental function was normal and her mood was not depressed. She was alert, cooperative and there was no evidence of somnolence or memory dysfunction. Her motor examination showed mild to moderate bilateral cogwheel rigidity in the upper extremeties and moderate bilateral slowing of ®nger and hand movements. She had no tremor or dyskinesias. Her gait and balance were excellent. Her medications included carbidopa/levodopa 25/100 mg TID, amantadine 100 mg BID and sertraline 100 mg daily. She * Corresponding author. Tel: 11-305-243-6332; fax: 11-305-243-4678.
scored 13 on the Epworth Sleepiness Scale (ESS) [3] indicating she had signi®cant daytime sleepiness. Moda®nil 200 mg qAM was initiated for one week and increased to 400 mg qAM. Within 2 weeks she reported improvement in EDS. On return to the movement disorder clinic three months later the patient reported considerable subjective improvement in her EDS and her ESS score had dropped to 8 (nonsigni®cant EDS). She reported a mild increase in tremor in her right hand but no important functional change in her motor status. There were no adverse events associated with moda®nil use. On repeat examination her motor ®ndings were stable and unchanged. Sleep disturbance in PD ranges from nocturnal vocalizations, vivid nightmares, REM sleep disorder to marked failure to initiate sleep and sleep fragmentation. EDS is quite prevalent and often represents a very signi®cant problem in the management of PD. The ef®cacy of moda®nil in the treatment of EDS has been reported in narcolepsy [4,5]. Although the mechanism of action of this drug effect is not yet established preclinical data has been published suggesting that it may ameliorate both MPTP induced dopaminergic cell damage in the mouse and glutamate induced cytotoxicity in cultured cortical neurons [6]. Either of these potential effects makes the compound of increased interest in PD. Moda®nil does not seem to affect the extrapyramidal motor system as do other psychostimulants such as amphetamine [7] and this combined with its lower potential for dependency and abuse [2], make it a possible option for the treatment of EDS in PD patients. Although not listed as an
1353-8020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S 1353-802 0(00)00035-3
288
A. Rabinstein et al. / Parkinsonism and Related Disorders 7 (2001) 287±288
adverse event in the pivotal studies of moda®nil in narcolepsy, the package insert states that occasional elderly patients developed oro-facial dyskinesias [4,5]. This may prove to be a troublesome adverse event in patients with PD. Our patient did not develop any dyskinesia when moda®nil was added to her carbidopa/levodopa, amantadine and sertraline. It is unlikely that sertraline was responsible for the EDS since the patient had been taking it for nine months with no reported somnolence. Even if sertraline was contributing to her EDS it is still noteworthy that moda®nil relieved her symptoms. We report the successful treatment of EDS in PD with moda®nil. We believe that further studies should be undertaken in order to de®ne the potential role of moda®nil in the management of patients with PD. Acknowledgements This work supported in part by The Rosalyn Newman Foundation and The National Parkinson Foundation.
References [1] Karslen KH, Larsen JP, Tandberg E, Mealand JG. In¯uence of clinical and demographic variables on quality of life in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1999;66(4):431±5. [2] Anonymous. Moda®nil for narcolepsy. Med Lett Drugs Ther 1999;41(1049):30±1. [3] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14(6):540±5. [4] Laffont F, Mayer G, Minz M. Moda®nil in diurnal sleepiness. A study of 123 patients. Sleep 1994;17(8):S113±5. [5] US Moda®nil in Narcolepsy Multicenter Study Group. Randomized trial of moda®nil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998;43(1):88±97. [6] Antonelli T, Ferraro L, Hillion J, Tomasini MC, Rambert FA, Fuxe K. Moda®nil prevents glutamate cytotoxicity in cultured cortical neurons. Neuroreport 1998;9(18):4209±13. [7] Engber TM, Dennis SA, Jones BE, Miller MS, Contreras PC. Brain regional substrates for the actions of the novel wake-promoting agent moda®nil in the rat: comparison with amphetamine. Neuroscience 1998;87(4):905±11.