- Email: [email protected]
Zolpidem-induced sleep-related eating disorder
Journal of the Neurological Sciences 288 (2010) 200–201
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Zolpidem-induced sleep-related eating disorder Chang-Ho Yun ⁎, Ki-Hwan Ji Department of Neurology, Inha University Hospital, 7-206 Shinheung-dong, 3-ga Joong-gu, Incheon 400-711, Republic of Korea
a r t i c l e
i n f o
Article history: Received 23 June 2009 Received in revised form 23 September 2009 Accepted 23 September 2009 Available online 12 October 2009
a b s t r a c t An association between zolpidem administration and sleep-related eating disorder (SRED) has been suggested. The authors observed zolpidem-induced SRED in restless legs syndrome (RLS). With the review of previous reports, we identified a common occurrence of RLS in zolpidem-induced SRED. © 2009 Elsevier B.V. All rights reserved.
Keywords: Parasomnia Restless legs syndrome Insomnia Non-benzodiazepine receptor agonist Hypnotic Adverse effect Dopamine
1. Introduction Sleep-related eating disorder (SRED) is characterized by recurrent nocturnal eating episodes in the middle of sleep leading to physical injury, morning anorexia or weight gain [1]. Patients are partly or fully amnestic about episodes, which differentiates SRED from nocturnal eating syndrome [2]. The pathomechanism of SRED is still uncertain but it has been suggested to be related to dopaminergic dysfunction, which is supported by the increased prevalence of SRED in restless legs syndrome (RLS), response to dopaminergic medication and increased periodic limb movements during sleep [2–6]. Furthermore, SRED can be induced by medication, especially zolpidem [7–10]. We report zolpidem-induced SRED in a patient with underlying RLS and review the related literatures. 2. Case report A 45-year-old man presented with bizarre eating behavior at night. For 5 years, he had suffered from nocturnal leg discomfort, described as a combination of burning, creeping, or pushing sensations. Symptoms normally began at around 9 pm, 2 h before bed time, and were always associated with restlessness and an irresistible urge to move. Symptoms worsened with inactivity, but were partially alleviated by activity. For 2 years, symptoms had occurred daily and been severe enough to impair sleep. As symptoms worsened, symptomatic area expanded from the calves to the thighs and pelvis. He had been taking meloxicam (15 mg/day) and gabapentin (300 mg/day) at bedtime ⁎ Corresponding author. Tel.: +82 32 890 3418; fax: +82 32 890 3864. E-mail address: [email protected] (C.-H. Yun). 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.09.026
under a diagnosis of unspecified neuralgia, but they did not provide complete or consistent relief. A previous evaluation of peripheral neuropathy, radiculopathy, circulation disorders and rheumatologic diseases conducted 2 years before revealed no abnormality. To fall asleep, he had started to take zolpidem (10 mg) in immediate release form twice per week on average. He usually went to bed at 11 pm and it took more than 1 h to fall asleep after taking zolpidem. He increased the frequency of zolpidem as leg symptoms worsened and at presentation had been taking it daily for 6 months. However, a couple of weeks later, family members noticed bizarre eating behaviors. Usually 2 h after he fell asleep, he suddenly left the bed, walked into the kitchen, picked up foods, sat at the table, and ate whatever he picked. He usually ate steamed rice in the cooker without side dishes, snacks from a cupboard or canned tuna from the refrigerator. Occasionally he cooked instant noodles, but was never burned while boiling water. His nocturnal food preference was not unusual, other than at regular meals he usually ate steamed rice with some side dishes. Intake amounts were similar to daytime meals. After eating, he went back to bed. These episodes occurred two or three times a week and lasted 20– 30 min. The kitchen was always left in a mess. He was never able to recall any part of any episode, but only guessed what happened due to abdominal bloating and the state of kitchen. He had been on an ordinary daytime diet without a history of eating disorders, and had gained 10 kg in weight over 6 months (from 67 to 77 kg). At presentation, he complained of unrefreshing sleep and had Epworth sleepiness scale score of seven and RLS rating scale of 39 with a normal serum ferritin (121.8 ng/ml) [11]. He had no personal and family history of sleepwalking, depression, substance abuse, or narcolepsy. He was a non-smoker and did not consume alcohol. Nocturnal polysomnography was performed 2 days after we had discontinued
C.-H. Yun, K.-H. Ji / Journal of the Neurological Sciences 288 (2010) 200–201
zolpidem and started pramipexole (0.125 mg) and clonazepam (0.25 mg) at bedtime. Sleep latency was 10 min with apnea–hypopnea index 2.6, sleep efficiency 84.3%, and reduced stage N3. There was no evidence of bizarre eating, arousal disorders, periodic limb movements or epileptic seizures on polysomnography. After zolpidem discontinuation, SRED did not recur at all over 6 months of follow-up. RLS and related insomnia were controlled with pramipexole 0.5 mg and clonazepam 0.25 mg a day with RLS rating scale of 12. 3. Discussion Typical clinical features, namely, amnestic nocturnal eating behaviors and sensorimotor symptoms in both legs with circadian fluctuations, supported a diagnosis of SRED and RLS in our patient. Zolpidem is presumed to have precipitated the SRED in our case, based on the close temporal relationship between SRED manifestations and the change in zolpidem intake. Zolpidem-induced SRED has been reported in nine subjects in the medical literatures [7–10], and including our subject, starting (n = 7) or increasing (n = 3) zolpidem dosage resulted in the development (n = 8) or aggravation (n = 2) of SRED, and removing (n = 8) or reducing (n = 2) zolpidem resolved SRED. Age of onset was 58.8 ± 11.1 years with no gender predilection (female, 50%). Specific sleepwalking descriptions were available for seven. Only one (14.3%) had a single episode of suspected sleepwalking (falling out of bed) during her college years [7]. RLS history was available for eight and not specifically described in two. Interestingly, all eight had underlying RLS. On the other hand, SRED in the general and clinical populations had been characterized as having an adolescent to young adulthood onset, a female preponderance, a higher prevalence of sleepwalking (at least 50%), and chronic course of more than a decade [2–4]. Dopaminergic dysfunction has been suggested in SRED based on the following evidence. Clinical response to dopaminergic drugs was well-documented in SRED [2–4]. Also, RLS and PLMS have been commonly associated with SRED [2–4]. Recently, an Italian group confirmed the higher prevalence of periodic limb movements or RLS dyskinesia (77.1%) and periodic activations in orbicularis oculi and masticator muscles (82.9%) by video-polysomnography [5]. The same group documented a much higher prevalence of SRED in RLS subjects (33%) than in normal controls (1%) [6]. Reported prevalence in psychiatric and nonpsychiatric population was 4.7% [12]. Circadian fluctuation in both RLS and SRED is a well-established phenomenon. No association between RLS and nocturnal eating syndrome or any other daytime eating disorder is notable [6]. In addition, compulsive eating has been reported in Parkinson's disease [13]. Dopaminergic dysfunction is the key mechanism of RLS, periodic limb movements, and Parkinson's disease [13,14]. Furthermore, dopamine is the principal mediator of the mesolimbic reward mechanism [15]. Therefore, dopaminergic dysfunction may contribute to the association between RLS and SRED. Hypnotics have been known to induce amnestic complex behaviors [16]. Zolpidem, like other non-benzodiazepine receptor agonists such as zaleplone and eszopiclone, selectively acts on the GABAA receptor (particularly α1-GABAA subtype) that mediates sedative and amnestic effects. It has been suggested that complex behavior risks increase with both dose and binding affinity at α1-GABAA receptors [16]. The dose used in zolpidem-induced amnestic somnambulism has been reported to be higher than in control insomnia [17]. Furthermore, zolpidem has the highest receptor-binding affinity among the non-benzodiazepine receptor agonists, which may explain its more frequent association with
201
hypnosedative complex behavior [16]. One report has been issued on the reversal of SRED by changing hypnotics from zolpidem to eszopiclone [8]. Zolpidem formulation was implicated in two SRED subjects, because SRED was triggered by a change from the immediate (10 mg/day) to the controlled-release (12.5 mg/day) form and reversed by switching back to the immediate release form [10]. But the CNS drug concentration is the key factor rather than the type of the formulation used because 7 of 10 cases of zolpidem-induced SRED had taken the immediate form [7,9]. We reported a case of zolpidem-induced SRED. Based on our literature review, we stress the common association between this condition and RLS. This case cautions that the possibility of SRED should be considered when physicians prescribe hypnotics in RLS. Disclosure statement All authors have no financial conflict of interests. Acknowledgment This work was supported by INHA UNIVERSITY Research Grant. References [1] American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 2nd ed. Westchester, Ill.: American Academy of Sleep Medicine; 2005. p. 173–5. [2] Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry 1998;59(1):14–9. [3] Schenck CH, Hurwitz TD, Bundlie SR, Mahowald MW. Sleep-related eating disorders: polysomnographic correlates of a heterogeneous syndrome distinct from daytime eating disorders. Sleep 1991;14(5):419–31. [4] Schenck CH, Hurwitz TD, O'Connor KA, Mahowald MW. Additional categories of sleep-related eating disorders and the current status of treatment. Sleep 1993;16 (5):457–66. [5] Vetrugno R, Manconi M, Ferini-Strambi L, Provini F, Plazzi G, Montagna P. Nocturnal eating: sleep-related eating disorder or night eating syndrome? A videopolysomnographic study. Sleep 2006;29(7):949–54. [6] Provini F, Antelmi E, Vignatelli L, Zaniboni A, Naldi G, Calandra-Buonaura G, et al. Association of restless legs syndrome with nocturnal eating: a case-control study. Mov Disord 2009;24(6):871–7. [7] Morgenthaler TI, Silber MH. Amnestic sleep-related eating disorder associated with zolpidem. Sleep Med 2002;3(4):323–7. [8] Najjar M. Zolpidem and amnestic sleep related eating disorder. J Clin Sleep Med 2007;3(6):637–8. [9] Dang A, Garg G, Rataboli PV. Zolpidem induced nocturnal sleep-related eating disorder (NSRED) in a male patient. Int J Eat Disord 2009;42(4):385–6. [10] Chiang A, Krystal A. Report of two cases where sleep related eating behavior occurred with the extended-release formulation but not the immediate-release formulation of a sedative-hypnotic agent. J Clin Sleep Med 2008;4(2):155–6. [11] Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003;4(2):121–32. [12] Winkelman JW, Herzog DB, Fava M. The prevalence of sleep-related eating disorder in psychiatric and non-psychiatric populations. Psychol Med 1999;29 (6):1461–6. [13] Evans AH, Strafella AP, Weintraub D, Stacy M. Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord 2009;24(11):1561–70. [14] Paulus W, Dowling P, Rijsman R, Stiasny-Kolster K, Trenkwalder C, de Weerd A. Pathophysiological concepts of restless legs syndrome. Mov Disord 2007;22 (10):1451–6. [15] Blum K, Wood RC, Braverman ER, Chen TJ, Sheridan PJ. The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes' theorem. Funct Neurol 1995;10 (1):37–44. [16] Dolder CR, Nelson MH. Hypnosedative-induced complex behaviours: incidence, mechanisms and management. CNS Drugs 2008;22(12):1021–36. [17] Tsai JH, Yang P, Chen CC, Chung W, Tang TC, Wang SY, et al. Zolpidem-induced amnesia and somnambulism: rare occurrences? Eur Neuropsychopharmacol 2009;19(1):74–6.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Zolpidem-induced sleep-related eating disorder Chang-Ho Yun ⁎, Ki-Hwan Ji Department of Neurology, Inha University Hospital, 7-206 Shinheung-dong, 3-ga Joong-gu, Incheon 400-711, Republic of Korea
a r t i c l e
i n f o
Article history: Received 23 June 2009 Received in revised form 23 September 2009 Accepted 23 September 2009 Available online 12 October 2009
a b s t r a c t An association between zolpidem administration and sleep-related eating disorder (SRED) has been suggested. The authors observed zolpidem-induced SRED in restless legs syndrome (RLS). With the review of previous reports, we identified a common occurrence of RLS in zolpidem-induced SRED. © 2009 Elsevier B.V. All rights reserved.
Keywords: Parasomnia Restless legs syndrome Insomnia Non-benzodiazepine receptor agonist Hypnotic Adverse effect Dopamine
1. Introduction Sleep-related eating disorder (SRED) is characterized by recurrent nocturnal eating episodes in the middle of sleep leading to physical injury, morning anorexia or weight gain [1]. Patients are partly or fully amnestic about episodes, which differentiates SRED from nocturnal eating syndrome [2]. The pathomechanism of SRED is still uncertain but it has been suggested to be related to dopaminergic dysfunction, which is supported by the increased prevalence of SRED in restless legs syndrome (RLS), response to dopaminergic medication and increased periodic limb movements during sleep [2–6]. Furthermore, SRED can be induced by medication, especially zolpidem [7–10]. We report zolpidem-induced SRED in a patient with underlying RLS and review the related literatures. 2. Case report A 45-year-old man presented with bizarre eating behavior at night. For 5 years, he had suffered from nocturnal leg discomfort, described as a combination of burning, creeping, or pushing sensations. Symptoms normally began at around 9 pm, 2 h before bed time, and were always associated with restlessness and an irresistible urge to move. Symptoms worsened with inactivity, but were partially alleviated by activity. For 2 years, symptoms had occurred daily and been severe enough to impair sleep. As symptoms worsened, symptomatic area expanded from the calves to the thighs and pelvis. He had been taking meloxicam (15 mg/day) and gabapentin (300 mg/day) at bedtime ⁎ Corresponding author. Tel.: +82 32 890 3418; fax: +82 32 890 3864. E-mail address: [email protected] (C.-H. Yun). 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.09.026
under a diagnosis of unspecified neuralgia, but they did not provide complete or consistent relief. A previous evaluation of peripheral neuropathy, radiculopathy, circulation disorders and rheumatologic diseases conducted 2 years before revealed no abnormality. To fall asleep, he had started to take zolpidem (10 mg) in immediate release form twice per week on average. He usually went to bed at 11 pm and it took more than 1 h to fall asleep after taking zolpidem. He increased the frequency of zolpidem as leg symptoms worsened and at presentation had been taking it daily for 6 months. However, a couple of weeks later, family members noticed bizarre eating behaviors. Usually 2 h after he fell asleep, he suddenly left the bed, walked into the kitchen, picked up foods, sat at the table, and ate whatever he picked. He usually ate steamed rice in the cooker without side dishes, snacks from a cupboard or canned tuna from the refrigerator. Occasionally he cooked instant noodles, but was never burned while boiling water. His nocturnal food preference was not unusual, other than at regular meals he usually ate steamed rice with some side dishes. Intake amounts were similar to daytime meals. After eating, he went back to bed. These episodes occurred two or three times a week and lasted 20– 30 min. The kitchen was always left in a mess. He was never able to recall any part of any episode, but only guessed what happened due to abdominal bloating and the state of kitchen. He had been on an ordinary daytime diet without a history of eating disorders, and had gained 10 kg in weight over 6 months (from 67 to 77 kg). At presentation, he complained of unrefreshing sleep and had Epworth sleepiness scale score of seven and RLS rating scale of 39 with a normal serum ferritin (121.8 ng/ml) [11]. He had no personal and family history of sleepwalking, depression, substance abuse, or narcolepsy. He was a non-smoker and did not consume alcohol. Nocturnal polysomnography was performed 2 days after we had discontinued
C.-H. Yun, K.-H. Ji / Journal of the Neurological Sciences 288 (2010) 200–201
zolpidem and started pramipexole (0.125 mg) and clonazepam (0.25 mg) at bedtime. Sleep latency was 10 min with apnea–hypopnea index 2.6, sleep efficiency 84.3%, and reduced stage N3. There was no evidence of bizarre eating, arousal disorders, periodic limb movements or epileptic seizures on polysomnography. After zolpidem discontinuation, SRED did not recur at all over 6 months of follow-up. RLS and related insomnia were controlled with pramipexole 0.5 mg and clonazepam 0.25 mg a day with RLS rating scale of 12. 3. Discussion Typical clinical features, namely, amnestic nocturnal eating behaviors and sensorimotor symptoms in both legs with circadian fluctuations, supported a diagnosis of SRED and RLS in our patient. Zolpidem is presumed to have precipitated the SRED in our case, based on the close temporal relationship between SRED manifestations and the change in zolpidem intake. Zolpidem-induced SRED has been reported in nine subjects in the medical literatures [7–10], and including our subject, starting (n = 7) or increasing (n = 3) zolpidem dosage resulted in the development (n = 8) or aggravation (n = 2) of SRED, and removing (n = 8) or reducing (n = 2) zolpidem resolved SRED. Age of onset was 58.8 ± 11.1 years with no gender predilection (female, 50%). Specific sleepwalking descriptions were available for seven. Only one (14.3%) had a single episode of suspected sleepwalking (falling out of bed) during her college years [7]. RLS history was available for eight and not specifically described in two. Interestingly, all eight had underlying RLS. On the other hand, SRED in the general and clinical populations had been characterized as having an adolescent to young adulthood onset, a female preponderance, a higher prevalence of sleepwalking (at least 50%), and chronic course of more than a decade [2–4]. Dopaminergic dysfunction has been suggested in SRED based on the following evidence. Clinical response to dopaminergic drugs was well-documented in SRED [2–4]. Also, RLS and PLMS have been commonly associated with SRED [2–4]. Recently, an Italian group confirmed the higher prevalence of periodic limb movements or RLS dyskinesia (77.1%) and periodic activations in orbicularis oculi and masticator muscles (82.9%) by video-polysomnography [5]. The same group documented a much higher prevalence of SRED in RLS subjects (33%) than in normal controls (1%) [6]. Reported prevalence in psychiatric and nonpsychiatric population was 4.7% [12]. Circadian fluctuation in both RLS and SRED is a well-established phenomenon. No association between RLS and nocturnal eating syndrome or any other daytime eating disorder is notable [6]. In addition, compulsive eating has been reported in Parkinson's disease [13]. Dopaminergic dysfunction is the key mechanism of RLS, periodic limb movements, and Parkinson's disease [13,14]. Furthermore, dopamine is the principal mediator of the mesolimbic reward mechanism [15]. Therefore, dopaminergic dysfunction may contribute to the association between RLS and SRED. Hypnotics have been known to induce amnestic complex behaviors [16]. Zolpidem, like other non-benzodiazepine receptor agonists such as zaleplone and eszopiclone, selectively acts on the GABAA receptor (particularly α1-GABAA subtype) that mediates sedative and amnestic effects. It has been suggested that complex behavior risks increase with both dose and binding affinity at α1-GABAA receptors [16]. The dose used in zolpidem-induced amnestic somnambulism has been reported to be higher than in control insomnia [17]. Furthermore, zolpidem has the highest receptor-binding affinity among the non-benzodiazepine receptor agonists, which may explain its more frequent association with
201
hypnosedative complex behavior [16]. One report has been issued on the reversal of SRED by changing hypnotics from zolpidem to eszopiclone [8]. Zolpidem formulation was implicated in two SRED subjects, because SRED was triggered by a change from the immediate (10 mg/day) to the controlled-release (12.5 mg/day) form and reversed by switching back to the immediate release form [10]. But the CNS drug concentration is the key factor rather than the type of the formulation used because 7 of 10 cases of zolpidem-induced SRED had taken the immediate form [7,9]. We reported a case of zolpidem-induced SRED. Based on our literature review, we stress the common association between this condition and RLS. This case cautions that the possibility of SRED should be considered when physicians prescribe hypnotics in RLS. Disclosure statement All authors have no financial conflict of interests. Acknowledgment This work was supported by INHA UNIVERSITY Research Grant. References [1] American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 2nd ed. Westchester, Ill.: American Academy of Sleep Medicine; 2005. p. 173–5. [2] Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry 1998;59(1):14–9. [3] Schenck CH, Hurwitz TD, Bundlie SR, Mahowald MW. Sleep-related eating disorders: polysomnographic correlates of a heterogeneous syndrome distinct from daytime eating disorders. Sleep 1991;14(5):419–31. [4] Schenck CH, Hurwitz TD, O'Connor KA, Mahowald MW. Additional categories of sleep-related eating disorders and the current status of treatment. Sleep 1993;16 (5):457–66. [5] Vetrugno R, Manconi M, Ferini-Strambi L, Provini F, Plazzi G, Montagna P. Nocturnal eating: sleep-related eating disorder or night eating syndrome? A videopolysomnographic study. Sleep 2006;29(7):949–54. [6] Provini F, Antelmi E, Vignatelli L, Zaniboni A, Naldi G, Calandra-Buonaura G, et al. Association of restless legs syndrome with nocturnal eating: a case-control study. Mov Disord 2009;24(6):871–7. [7] Morgenthaler TI, Silber MH. Amnestic sleep-related eating disorder associated with zolpidem. Sleep Med 2002;3(4):323–7. [8] Najjar M. Zolpidem and amnestic sleep related eating disorder. J Clin Sleep Med 2007;3(6):637–8. [9] Dang A, Garg G, Rataboli PV. Zolpidem induced nocturnal sleep-related eating disorder (NSRED) in a male patient. Int J Eat Disord 2009;42(4):385–6. [10] Chiang A, Krystal A. Report of two cases where sleep related eating behavior occurred with the extended-release formulation but not the immediate-release formulation of a sedative-hypnotic agent. J Clin Sleep Med 2008;4(2):155–6. [11] Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003;4(2):121–32. [12] Winkelman JW, Herzog DB, Fava M. The prevalence of sleep-related eating disorder in psychiatric and non-psychiatric populations. Psychol Med 1999;29 (6):1461–6. [13] Evans AH, Strafella AP, Weintraub D, Stacy M. Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord 2009;24(11):1561–70. [14] Paulus W, Dowling P, Rijsman R, Stiasny-Kolster K, Trenkwalder C, de Weerd A. Pathophysiological concepts of restless legs syndrome. Mov Disord 2007;22 (10):1451–6. [15] Blum K, Wood RC, Braverman ER, Chen TJ, Sheridan PJ. The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes' theorem. Funct Neurol 1995;10 (1):37–44. [16] Dolder CR, Nelson MH. Hypnosedative-induced complex behaviours: incidence, mechanisms and management. CNS Drugs 2008;22(12):1021–36. [17] Tsai JH, Yang P, Chen CC, Chung W, Tang TC, Wang SY, et al. Zolpidem-induced amnesia and somnambulism: rare occurrences? Eur Neuropsychopharmacol 2009;19(1):74–6.