CASE REPORT
Nocturnal Bruxism in a Patient With Behçet Disease and Posttraumatic Stress Disorder Successfully Treated With Gabapentin Hui-Ming Feng, MD,* Shin-Chang Kuo, MD,†‡ Chun-Yen Chen, MD,†‡ and Yi-Wei Yeh, MD†‡ Abstract: Bruxism is an involuntary movement, including teeth grinding and clenching, which occur primarily during sleep. Although Behçet disease and posttraumatic stress disorder both have a high prevalence of sleep problems, bruxism is extremely rare in these 2 disorders. Here, we report a rare case of concurrent Behçet disease and posttraumatic stress disorder, which presented with antidepressant-refractory sleep disturbance accompanied by teeth grinding, clenching, and snoring that was successfully treated with gabapentin. Key Words: bruxism, gabapentin, posttraumatic stress disorder, Behçet disease (Clin Neuropharm 2014;37: 190–191)
B
ehçet disease is a rare immune-related vasculitis that presents with recurrent aphthous ulcers, genital ulcers, and uveitis. Treatment for Behçet disease focuses on controlling the immune system, reducing inflammation, and relieving the symptoms. However, the high prevalence of sleep disorders in patients with Behçet disease is often ignored, and consequently, there is a lack of adequate treatment.1,2 Posttraumatic stress disorder (PTSD) is classified as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and is characterized by persistent flashbacks of past traumatic events, nightmares, avoidance of trauma-associated stimuli, general numbing of emotional responsiveness, and hypervigilance. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for patients with PTSD.3 Nevertheless, nightmares, insomnia, sleep apnea, and periodic limb movements, which are highly prevalent in patients with PTSD,4,5 often fail to respond to SSRIs. Bruxism is teeth grinding and clenching that occurs primarily during sleep. Although Behçet disease and PTSD both have a high prevalence of sleep problems, bruxism is extremely rare in these 2 disorders. Here, we report a rare case of concurrent Behçet disease and PTSD, which presented with antidepressant-refractory sleep disturbance accompanied by teeth grinding, clenching, and snoring that was successfully treated with gabapentin.
CASE REPORT
(10 mg), and salazine (2000 mg) as a rheumatologic outpatient and was fairly compliant. He took zolpidem at an initial dosage of 5 mg and gradually escalated to 20 mg. His PTSD symptoms, including flashback, nightmares, avoiding recalling the trauma, hypervigilance, and sleep disturbance, were not adequately treated and were worsening. He was referred to our psychiatric clinic because of frequent nightmares, interrupted sleep, daytime sleepiness, and fatigue, despite the fact that his Behçet disease was well controlled. His actual sleep duration was less than 4 hours and his sleep efficiency was less than 65%. Moreover, his wife reported loud teeth grinding, clenching, and snoring without notable apnea at bedtime. His score was 18 on the Pittsburgh Sleep Quality Index (PSQI) and 5 on the Clinical Global Impression— Severity scale (CGI-S). Twenty milligrams of paroxetine and 2 mg of clonazepam were initiated for the PTSD and sleeprelated symptoms. Cognitive behavior therapy and muscle relaxation training were used concurrently. After 16 weeks of treatment, most of the PTSD symptoms improved (CGI-S, 3; PSQI, 10), but the patient's wife still observed nocturnal bruxism and unbearably noisy snoring. The patient's body mass index was 20.0 kg/m2. On physical examination, his teeth were severely damaged because of longterm bruxism. There was no enlargement of uvula or tonsils, no micrognathia or retrognathia, and no malocclusion or temporomandibular joint dysfunction in this patient. The patient did not receive the oral appliance that had been suggested by his dentist because of its expensive cost. In addition, there was no indication for surgery after visiting an otolaryngologist. Therefore, pharmacotherapy with daily 300 mg of gabapentin was prescribed at bedtime as an adjuvant therapy for sleep bruxism after discussing with the patient. Within 1 week, the patient reported that bruxism resolved dramatically and that snoring improved subsequently. Moreover, gabapentin significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency, and time awake during the total sleep period (CGI-S, 2; PSQI, 5). When we tried to taper gabapentin, the bruxism and snoring recurred. The patient has been maintained on 20 mg of paroxetine, 300 mg of gabapentin, 2 mg of clonazepam, and 10 mg of zolpidem for 1 year; in addition, the patient and his wife have reported good sleep quality without obvious teeth grinding, clenching, or snoring.
The patient was a 37-year-old married man with a 14-year history of Behçet disease and a 17-year history of PTSD. He was taking azathioprine (75 mg), colchicine (0.5 mg), prednisolone
DISCUSSION
Departments of *Otolaryngology—Head and Neck Surgery and †Psychiatry, Tri-Service General Hospital, National Defense Medical Center; and ‡Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Address correspondence and reprint requests to Yi-Wei Yeh, MD, Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kung Rd, Nei-Hu Area, Taipei 11490, Taiwan; E-mail: [email protected] Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/WNF.0000000000000054
Our patient with concurrent Behçet disease and PTSD presented with residual sleep symptoms, such as bruxism and snoring, in spite of treatment with SSRIs and hypnotics. Clonazepam, which has been reported to have acute efficacy on sleep bruxism,6 was ineffective for our patient's bruxism. Bruxism and snoring did not improve until initiation of 300 mg of gabapentin daily. Gabapentin, an anticonvulsant agent, has been used as an adjunctive therapy for nightmares and insomnia in patients with PTSD.7 Gabapentin is also effective in the treatment of sleeprelated movement disorders,8 such as restless legs syndrome, and periodic limb movement disorder. Bruxism, which is classified
190
www.clinicalneuropharm.com
Clinical Neuropharmacology • Volume 37, Number 6, November/December 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Clinical Neuropharmacology • Volume 37, Number 6, November/December 2014
as a simple type of sleep-related movement disorder with orofacial/oromandibular movements, may therefore respond to gabapentin treatment as well as restless legs syndrome and periodic limb movement disorder. Moreover, an open-label trial that compared gabapentin with oral splints in the management of sleep bruxism showed comparable efficacy to oral splints.9 In the present case, a decrease in snoring was followed by improvement of sleep bruxism after initiating gabapentin. This indicates that the emergence of snoring may be secondary to the development of bruxism. However, the exact mechanism by which gabapentin treats sleep bruxism and snoring is unclear. Patients with sleep bruxism were found to have a decreased amount of slow-wave sleep (SWS).10 Blockade of voltage-gated calcium channels to influence calcium influx is considered to be the therapeutic mechanism of gabapentin in neuropathic pain. Therefore, gabapentin may improve sleep bruxism by modulating the basal ganglia through regulation of membrane potential oscillations,11 thereby increasing SWS to ameliorate sleep bruxism.12–14 In contrast, many antidepressants and hypnotics decrease or do not alter SWS. This could partially explain why several previous reports of antidepressant-induced bruxism15–17 and 1 case of venlafaxine-induced bruxism were successfully treated using gabapentin.18 It might also explain why gabapentin but not SSRIs or hypnotics was a successful treatment for the sleep bruxism in our patient. Patients with many rheumatologic disorders and psychiatric disorders often experience concurrent sleep-related disorders.19 Either sleep bruxism or snoring can produce many brief arousals, leading to poor sleep quality. Nevertheless, no effective pharmacotherapy is recommended for the treatment of sleep bruxism or snoring currently. We believe that this case may provide a treatment option for complex sleep disorders in patients with concurrent rheumatologic and psychiatric disorders. The limitations in this case are that our finding was based on subjective information of self-reported and clinician-assessed findings and that this case lacks polysomnographic record. Therefore, placebo effect of gabapentin cannot be ruled out entirely; however, we believed that it is less likely in the present case because we observed that the symptoms of bruxism and snoring recurred while tapering gabapentin and that the symptoms ameliorated after resuming medication. Further prospective, controlled study with polysomnographic records is needed to validate the efficacy of gabapentin in the treatment of sleep bruxism and snoring in these patients. REFERENCES
Gabapentin Treatment of Sleep Bruxism
3. Asnis GM, Kohn SR, Henderson M, et al. SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with recommendations. Drugs 2004;64(4):383–404. 4. Maher MJ, Rego SA, Asnis GM. Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management. CNS Drugs 2006;20(7):567–590. 5. Lavie P, Katz N, Pillar G, et al. Elevated awaking thresholds during sleep: characteristics of chronic war-related posttraumatic stress disorder patients. Biol Psychiatry 1998;44(10):1060–1065. 6. Saletu A, Parapatics S, Anderer P, et al. Controlled clinical, polysomnographic and psychometric studies on differences between sleep bruxers and controls and acute effects of clonazepam as compared with placebo. Eur Arch Psychiatry Clin Neurosci 2010;260(2):163–174. 7. Hamner MB, Brodrick PS, Labbate LA. Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy. Ann Clin Psychiatry 2001;13(3):141–146. 8. Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults—an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012;35(8):1039–1062. 9. Madani AS, Abdollahian E, Khiavi HA, et al. The efficacy of gabapentin versus stabilization splint in management of sleep bruxism. J Prosthodont 2013;22(2):126–131. 10. Nagels G, Okkerse W, Braem M, et al. Decreased amount of slow wave sleep in nocturnal bruxism is not improved by dental splint therapy. Acta Neurol Belg 2001;101(3):152–159. 11. Rahman W, Dickenson AH. Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain. Neurosci Lett 2013;557 Pt A:19–26. 12. Placidi F, Mattia D, Romigi A, et al. Gabapentin-induced modulation of interictal epileptiform activity related to different vigilance levels. Clin Neurophysiol 2000;111(9):1637–1642. 13. Legros B, Bazil CW. Effects of antiepileptic drugs on sleep architecture: a pilot study. Sleep Med 2003;4(1):51–55. 14. Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, et al. Gabapentin increases slow-wave sleep in normal adults. Epilepsia 2002;43(12): 1493–1497. 15. Albayrak Y, Ekinci O. Duloxetine-induced nocturnal bruxism resolved by buspirone: case report. Clin Neuropharmacol 2011;34(4):137–138. 16. Alonso-Navarro H, Martín-Prieto M, Ruiz-Ezquerro JJ, et al. Bruxism possibly induced by venlafaxine. Clin Neuropharmacol 2009;32(2): 111–112. 17. Ellison JM, Stanziani P. SSRI-associated nocturnal bruxism in four patients. J Clin Psychiatry 1993;54(11):432–434.
1. Tascilar NF, Tekin NS, Ankarali H, et al. Sleep disorders in Behçet's disease, and their relationship with fatigue and quality of life. J Sleep Res 2012;21(3):281–288.
18. Brown ES, Hong SC. Antidepressant-induced bruxism successfully treated with gabapentin. J Am Dent Assoc 1999;130(10):1467–1469.
2. Ediz L, Hiz O, Toprak M, et al. Restless legs syndrome in Behçet's disease. J Int Med Res 2011;39(3):759–765.
19. Abad VC, Sarinas PS, Guilleminault C. Sleep and rheumatologic disorders. Sleep Med Rev 2008;12(3):211–228.
© 2014 Lippincott Williams & Wilkins
www.clinicalneuropharm.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
191
Nocturnal Bruxism in a Patient With Behçet Disease and Posttraumatic Stress Disorder Successfully Treated With Gabapentin Hui-Ming Feng, MD,* Shin-Chang Kuo, MD,†‡ Chun-Yen Chen, MD,†‡ and Yi-Wei Yeh, MD†‡ Abstract: Bruxism is an involuntary movement, including teeth grinding and clenching, which occur primarily during sleep. Although Behçet disease and posttraumatic stress disorder both have a high prevalence of sleep problems, bruxism is extremely rare in these 2 disorders. Here, we report a rare case of concurrent Behçet disease and posttraumatic stress disorder, which presented with antidepressant-refractory sleep disturbance accompanied by teeth grinding, clenching, and snoring that was successfully treated with gabapentin. Key Words: bruxism, gabapentin, posttraumatic stress disorder, Behçet disease (Clin Neuropharm 2014;37: 190–191)
B
ehçet disease is a rare immune-related vasculitis that presents with recurrent aphthous ulcers, genital ulcers, and uveitis. Treatment for Behçet disease focuses on controlling the immune system, reducing inflammation, and relieving the symptoms. However, the high prevalence of sleep disorders in patients with Behçet disease is often ignored, and consequently, there is a lack of adequate treatment.1,2 Posttraumatic stress disorder (PTSD) is classified as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and is characterized by persistent flashbacks of past traumatic events, nightmares, avoidance of trauma-associated stimuli, general numbing of emotional responsiveness, and hypervigilance. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for patients with PTSD.3 Nevertheless, nightmares, insomnia, sleep apnea, and periodic limb movements, which are highly prevalent in patients with PTSD,4,5 often fail to respond to SSRIs. Bruxism is teeth grinding and clenching that occurs primarily during sleep. Although Behçet disease and PTSD both have a high prevalence of sleep problems, bruxism is extremely rare in these 2 disorders. Here, we report a rare case of concurrent Behçet disease and PTSD, which presented with antidepressant-refractory sleep disturbance accompanied by teeth grinding, clenching, and snoring that was successfully treated with gabapentin.
CASE REPORT
(10 mg), and salazine (2000 mg) as a rheumatologic outpatient and was fairly compliant. He took zolpidem at an initial dosage of 5 mg and gradually escalated to 20 mg. His PTSD symptoms, including flashback, nightmares, avoiding recalling the trauma, hypervigilance, and sleep disturbance, were not adequately treated and were worsening. He was referred to our psychiatric clinic because of frequent nightmares, interrupted sleep, daytime sleepiness, and fatigue, despite the fact that his Behçet disease was well controlled. His actual sleep duration was less than 4 hours and his sleep efficiency was less than 65%. Moreover, his wife reported loud teeth grinding, clenching, and snoring without notable apnea at bedtime. His score was 18 on the Pittsburgh Sleep Quality Index (PSQI) and 5 on the Clinical Global Impression— Severity scale (CGI-S). Twenty milligrams of paroxetine and 2 mg of clonazepam were initiated for the PTSD and sleeprelated symptoms. Cognitive behavior therapy and muscle relaxation training were used concurrently. After 16 weeks of treatment, most of the PTSD symptoms improved (CGI-S, 3; PSQI, 10), but the patient's wife still observed nocturnal bruxism and unbearably noisy snoring. The patient's body mass index was 20.0 kg/m2. On physical examination, his teeth were severely damaged because of longterm bruxism. There was no enlargement of uvula or tonsils, no micrognathia or retrognathia, and no malocclusion or temporomandibular joint dysfunction in this patient. The patient did not receive the oral appliance that had been suggested by his dentist because of its expensive cost. In addition, there was no indication for surgery after visiting an otolaryngologist. Therefore, pharmacotherapy with daily 300 mg of gabapentin was prescribed at bedtime as an adjuvant therapy for sleep bruxism after discussing with the patient. Within 1 week, the patient reported that bruxism resolved dramatically and that snoring improved subsequently. Moreover, gabapentin significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency, and time awake during the total sleep period (CGI-S, 2; PSQI, 5). When we tried to taper gabapentin, the bruxism and snoring recurred. The patient has been maintained on 20 mg of paroxetine, 300 mg of gabapentin, 2 mg of clonazepam, and 10 mg of zolpidem for 1 year; in addition, the patient and his wife have reported good sleep quality without obvious teeth grinding, clenching, or snoring.
The patient was a 37-year-old married man with a 14-year history of Behçet disease and a 17-year history of PTSD. He was taking azathioprine (75 mg), colchicine (0.5 mg), prednisolone
DISCUSSION
Departments of *Otolaryngology—Head and Neck Surgery and †Psychiatry, Tri-Service General Hospital, National Defense Medical Center; and ‡Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Address correspondence and reprint requests to Yi-Wei Yeh, MD, Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kung Rd, Nei-Hu Area, Taipei 11490, Taiwan; E-mail: [email protected] Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/WNF.0000000000000054
Our patient with concurrent Behçet disease and PTSD presented with residual sleep symptoms, such as bruxism and snoring, in spite of treatment with SSRIs and hypnotics. Clonazepam, which has been reported to have acute efficacy on sleep bruxism,6 was ineffective for our patient's bruxism. Bruxism and snoring did not improve until initiation of 300 mg of gabapentin daily. Gabapentin, an anticonvulsant agent, has been used as an adjunctive therapy for nightmares and insomnia in patients with PTSD.7 Gabapentin is also effective in the treatment of sleeprelated movement disorders,8 such as restless legs syndrome, and periodic limb movement disorder. Bruxism, which is classified
190
www.clinicalneuropharm.com
Clinical Neuropharmacology • Volume 37, Number 6, November/December 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Clinical Neuropharmacology • Volume 37, Number 6, November/December 2014
as a simple type of sleep-related movement disorder with orofacial/oromandibular movements, may therefore respond to gabapentin treatment as well as restless legs syndrome and periodic limb movement disorder. Moreover, an open-label trial that compared gabapentin with oral splints in the management of sleep bruxism showed comparable efficacy to oral splints.9 In the present case, a decrease in snoring was followed by improvement of sleep bruxism after initiating gabapentin. This indicates that the emergence of snoring may be secondary to the development of bruxism. However, the exact mechanism by which gabapentin treats sleep bruxism and snoring is unclear. Patients with sleep bruxism were found to have a decreased amount of slow-wave sleep (SWS).10 Blockade of voltage-gated calcium channels to influence calcium influx is considered to be the therapeutic mechanism of gabapentin in neuropathic pain. Therefore, gabapentin may improve sleep bruxism by modulating the basal ganglia through regulation of membrane potential oscillations,11 thereby increasing SWS to ameliorate sleep bruxism.12–14 In contrast, many antidepressants and hypnotics decrease or do not alter SWS. This could partially explain why several previous reports of antidepressant-induced bruxism15–17 and 1 case of venlafaxine-induced bruxism were successfully treated using gabapentin.18 It might also explain why gabapentin but not SSRIs or hypnotics was a successful treatment for the sleep bruxism in our patient. Patients with many rheumatologic disorders and psychiatric disorders often experience concurrent sleep-related disorders.19 Either sleep bruxism or snoring can produce many brief arousals, leading to poor sleep quality. Nevertheless, no effective pharmacotherapy is recommended for the treatment of sleep bruxism or snoring currently. We believe that this case may provide a treatment option for complex sleep disorders in patients with concurrent rheumatologic and psychiatric disorders. The limitations in this case are that our finding was based on subjective information of self-reported and clinician-assessed findings and that this case lacks polysomnographic record. Therefore, placebo effect of gabapentin cannot be ruled out entirely; however, we believed that it is less likely in the present case because we observed that the symptoms of bruxism and snoring recurred while tapering gabapentin and that the symptoms ameliorated after resuming medication. Further prospective, controlled study with polysomnographic records is needed to validate the efficacy of gabapentin in the treatment of sleep bruxism and snoring in these patients. REFERENCES
Gabapentin Treatment of Sleep Bruxism
3. Asnis GM, Kohn SR, Henderson M, et al. SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with recommendations. Drugs 2004;64(4):383–404. 4. Maher MJ, Rego SA, Asnis GM. Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management. CNS Drugs 2006;20(7):567–590. 5. Lavie P, Katz N, Pillar G, et al. Elevated awaking thresholds during sleep: characteristics of chronic war-related posttraumatic stress disorder patients. Biol Psychiatry 1998;44(10):1060–1065. 6. Saletu A, Parapatics S, Anderer P, et al. Controlled clinical, polysomnographic and psychometric studies on differences between sleep bruxers and controls and acute effects of clonazepam as compared with placebo. Eur Arch Psychiatry Clin Neurosci 2010;260(2):163–174. 7. Hamner MB, Brodrick PS, Labbate LA. Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy. Ann Clin Psychiatry 2001;13(3):141–146. 8. Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults—an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012;35(8):1039–1062. 9. Madani AS, Abdollahian E, Khiavi HA, et al. The efficacy of gabapentin versus stabilization splint in management of sleep bruxism. J Prosthodont 2013;22(2):126–131. 10. Nagels G, Okkerse W, Braem M, et al. Decreased amount of slow wave sleep in nocturnal bruxism is not improved by dental splint therapy. Acta Neurol Belg 2001;101(3):152–159. 11. Rahman W, Dickenson AH. Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain. Neurosci Lett 2013;557 Pt A:19–26. 12. Placidi F, Mattia D, Romigi A, et al. Gabapentin-induced modulation of interictal epileptiform activity related to different vigilance levels. Clin Neurophysiol 2000;111(9):1637–1642. 13. Legros B, Bazil CW. Effects of antiepileptic drugs on sleep architecture: a pilot study. Sleep Med 2003;4(1):51–55. 14. Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, et al. Gabapentin increases slow-wave sleep in normal adults. Epilepsia 2002;43(12): 1493–1497. 15. Albayrak Y, Ekinci O. Duloxetine-induced nocturnal bruxism resolved by buspirone: case report. Clin Neuropharmacol 2011;34(4):137–138. 16. Alonso-Navarro H, Martín-Prieto M, Ruiz-Ezquerro JJ, et al. Bruxism possibly induced by venlafaxine. Clin Neuropharmacol 2009;32(2): 111–112. 17. Ellison JM, Stanziani P. SSRI-associated nocturnal bruxism in four patients. J Clin Psychiatry 1993;54(11):432–434.
1. Tascilar NF, Tekin NS, Ankarali H, et al. Sleep disorders in Behçet's disease, and their relationship with fatigue and quality of life. J Sleep Res 2012;21(3):281–288.
18. Brown ES, Hong SC. Antidepressant-induced bruxism successfully treated with gabapentin. J Am Dent Assoc 1999;130(10):1467–1469.
2. Ediz L, Hiz O, Toprak M, et al. Restless legs syndrome in Behçet's disease. J Int Med Res 2011;39(3):759–765.
19. Abad VC, Sarinas PS, Guilleminault C. Sleep and rheumatologic disorders. Sleep Med Rev 2008;12(3):211–228.
© 2014 Lippincott Williams & Wilkins
www.clinicalneuropharm.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
191
