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Mental Health Disorders Associated with RLS

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Restless Legs Syndrome/Willis Ekbom Disease
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Abstract

In this chapter, we cover the myriad ways that restless legs syndrome (RLS) and psychiatry interface. This particularly relevant because RLS was included as a unique sleep disorder in the recent Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Epidemiological data from both population and clinic-based studies have found a higher incidence of mental illness—particularly depressive and anxiety disorders—among cohorts with RLS. Conversely, preliminary data suggest that individuals with mental illness may have higher rates of RLS as well. We discuss neurobiological parallels between RLS and mental illness that may explain such comorbidity. We also consider the phenomenological overlap between RLS and neurocognitive impairment and attention-deficit/hyperactivity disorder. In general, patients with RLS tend to score higher on neuroticism on personality inventories. Data on whether serotonergic antidepressants worsen or improve RLS symptoms remain conflicting. Bupropion may be ideally suited for comorbid depression and RLS. We discuss the role of neuroleptics, sedative-hypnotics, and mood stabilizers in RLS, and we discuss how to differentiate RLS from neuroleptic-induced akathisia. We also review the psychiatric complications of common RLS treatment. We conclude with a practical approach to managing the often difficult situation of comorbid RLS and mental illness.

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References

  1. Wittmaack T. Pathologie und Therapie der Sensibilitäs Neurosens. Leipzig: E Schäfer; 1861.

    Google Scholar 

  2. Oppenheim H. Lehrbuch der Nervenkrankheiten. 7th ed. Berlin: Karger; 1923.

    Google Scholar 

  3. Gorman C, Dyck P, Pearson J. Symptom of restless legs. Arch Intern Med. 1965;115:155–60.

    Article  CAS  PubMed  Google Scholar 

  4. Ekbom K. The pre-senile delusion of infestation (classic text no. 54). Hist Psychiatry. 2003;14:229–56.

    Article  CAS  PubMed  Google Scholar 

  5. Ekbom K. Restless legs: a clinical study. Acta Med Scand. 1945;158:1–123.

    Google Scholar 

  6. Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep. 2005;28(7):891–8.

    PubMed  Google Scholar 

  7. American Psychiatric Association. Diagnostic and statistical manual for mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2013.

    Book  Google Scholar 

  8. Scholz H, Benes H, Happe S, Bengel J, Kohnen R, Hornyak M. Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study. Health Qual Life Outcomes. 2011;9:73.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Salas RE, Kwan AB. The real burden of restless legs syndrome: clinical and economic outcomes. Am J Managed Care. 2012;18(9 Suppl):S207–12.

    Google Scholar 

  10. Abetz L, Allen R, Follet A, Washburn T, Earley C, Kirsch J, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. 2004;26(6):925–35.

    Article  PubMed  Google Scholar 

  11. Kim JB, Koo YS, Eun MY, Park KW, Jung KY. Psychosomatic symptom profiles in patients with restless legs syndrome. Sleep Breathing = Schlaf & Atmung. 2013;17(3):1055–61.

    Google Scholar 

  12. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165(11):1286–92.

    Article  PubMed  Google Scholar 

  13. Ohayon MM, O’Hara R, Vitiello MV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. 2012;16(4):283–95.

    Article  PubMed  Google Scholar 

  14. Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry. 2005;62(10):1097–106.

    Article  PubMed  Google Scholar 

  15. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4(2):101–19.

    Article  PubMed  Google Scholar 

  16. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD Jr, et al. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry. 1984;41(10):949–58.

    Article  CAS  PubMed  Google Scholar 

  17. Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med. 2004;164(2):196–202.

    Article  PubMed  Google Scholar 

  18. Winkelmann J, Muller-Myhsok B, Wittchen HU, Hock B, Prager M, Pfister H, et al. Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families. Ann Neurol. 2002;52(3):297–302.

    Article  PubMed  Google Scholar 

  19. Kendler KS. The dappled nature of causes of psychiatric illness: replacing the organic-functional/hardware-software dichotomy with empirically based pluralism. Mol Psychiatry. 2012;17(4):377–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brand S, Lehtinen A, Hatzinger M, Holsboer-Trachsler E. Comparison of sleep EEG profiles of patients suffering from restless legs syndrome, restless legs syndrome and depressive symptoms, and major depressive disorders. Neuropsychobiology. 2010;61(1):41–8.

    Article  PubMed  Google Scholar 

  21. Broman JE, Mallon L, Hetta J. Restless legs syndrome and its relationship with insomnia symptoms and daytime distress: epidemiological survey in Sweden. Psychiatry Clin Neurosci. 2008;62(4):472–5.

    Article  PubMed  Google Scholar 

  22. Cuellar NG, Strumpf NE, Ratcliffe SJ. Symptoms of restless legs syndrome in older adults: outcomes on sleep quality, sleepiness, fatigue, depression, and quality of life. J Am Geriatr Soc. 2007;55(9):1387–92.

    Article  PubMed  Google Scholar 

  23. Ohayon MM, Roth T. Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. J Psychosom Res. 2002;53(1):547–54.

    Article  PubMed  Google Scholar 

  24. Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C. Epidemiology of restless legs symptoms in adults. Arch Intern Med. 2000;160(14):2137–41.

    Article  CAS  PubMed  Google Scholar 

  25. Winkelman JW, Finn L, Young T. Prevalence and correlates of restless legs syndrome symptoms in the Wisconsin Sleep Cohort. Sleep Med. 2006;7(7):545–52.

    Article  PubMed  Google Scholar 

  26. Ulfberg J, Bjorvatn B, Leissner L, Gyring J, Karlsborg M, Regeur L, et al. Comorbidity in restless legs syndrome among a sample of Swedish adults. Sleep Med. 2007;8(7–8):768–72.

    Article  PubMed  Google Scholar 

  27. Ulfberg J, Nystrom B, Carter N, Edling C. Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatric symptoms. Mov Disord (Official Journal Movement Disorder Society). 2001;16(6):1159–63.

    Article  CAS  Google Scholar 

  28. Wesstrom J, Nilsson S, Sundstrom-Poromaa I, Ulfberg J. Restless legs syndrome among women: prevalence, co-morbidity and possible relationship to menopause. Climacteric: J Int Menopause Soc. 2008;11(5):422–8.

    Article  CAS  Google Scholar 

  29. Bjorvatn B, Leissner L, Ulfberg J, Gyring J, Karlsborg M, Regeur L, et al. Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries. Sleep Med. 2005;6(4):307–12.

    Article  PubMed  Google Scholar 

  30. Kim KW, Yoon IY, Chung S, Shin YK, Lee SB, Choi EA, et al. Prevalence, comorbidities and risk factors of restless legs syndrome in the Korean elderly population—results from the Korean Longitudinal Study on Health and Aging. J Sleep Res. 2010;19(1 Pt 1):87–92.

    Article  PubMed  Google Scholar 

  31. Sevim S, Dogu O, Camdeviren H, Bugdayci R, Sasmaz T, Kaleagasi H, et al. Unexpectedly low prevalence and unusual characteristics of RLS in Mersin, Turkey. Neurology. 2003;61(11):1562–9.

    Article  CAS  PubMed  Google Scholar 

  32. Nomura T, Inoue Y, Kusumi M, Uemura Y, Nakashima K. Prevalence of restless legs syndrome in a rural community in Japan. Mov Disord (Official Journal Movement Disorder Society). 2008;23(16):2363–9.

    Article  Google Scholar 

  33. Celle S, Roche F, Kerleroux J, Thomas-Anterion C, Laurent B, Rouch I, et al. Prevalence and clinical correlates of restless legs syndrome in an elderly French population: the synapse study. J Gerontol Ser A, Biol Sci Med Sci. 2010;65(2):167–73.

    Article  Google Scholar 

  34. Winkelmann J, Prager M, Lieb R, Pfister H, Spiegel B, Wittchen HU, et al. “Anxietas tibiarum”. Depression and anxiety disorders in patients with restless legs syndrome. J Neurol. 2005;252(1):67–71.

    Article  CAS  PubMed  Google Scholar 

  35. Rothdach AJ, Trenkwalder C, Haberstock J, Keil U, Berger K. Prevalence and risk factors of RLS in an elderly population: the MEMO study. Memory and Morbidity in Augsburg Elderly. Neurology. 2000;54(5):1064–8.

    Article  CAS  PubMed  Google Scholar 

  36. Sevim S, Dogu O, Kaleagasi H, Aral M, Metin O, Camdeviren H. Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey. J Neurol Neurosurg Psychiatry. 2004;75(2):226–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lee HB, Hening WA, Allen RP, Kalaydjian AE, Earley CJ, Eaton WW, et al. Restless legs syndrome is associated with DSM-IV major depressive disorder and panic disorder in the community. J Neuropsychiatry Clin Neurosci. 2008;20(1):101–5.

    Article  PubMed  Google Scholar 

  38. Cho SJ, Hong JP, Hahm BJ, Jeon HJ, Chang SM, Cho MJ, et al. Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders. Sleep. 2009;32(8):1069–76.

    PubMed  PubMed Central  Google Scholar 

  39. Li Y, Mirzaei F, O’Reilly EJ, Winkelman J, Malhotra A, Okereke OI, et al. Prospective study of restless legs syndrome and risk of depression in women. Am J Epidemiol. 2012;176(4):279–88.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Szentkiralyi A, Volzke H, Hoffmann W, Baune BT, Berger K. The relationship between depressive symptoms and restless legs syndrome in two prospective cohort studies. Psychosom Med. 2013;75(4):359–65.

    Article  PubMed  Google Scholar 

  41. Aguera-Ortiz L, Perez MI, Osorio RS, Sacks H, Palomo T. Prevalence and clinical correlates of restless legs syndrome among psychogeriatric patients. Int J Geriatr Psychiatry. 2011;26(12):1252–9.

    Article  PubMed  Google Scholar 

  42. Kang SG, Lee HJ, Jung SW, Cho SN, Han C, Kim YK, et al. Characteristics and clinical correlates of restless legs syndrome in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(5):1078–83.

    Article  PubMed  Google Scholar 

  43. Jagota P, Asawavichienjinda T, Bhidayasiri R. Prevalence of neuroleptic-induced restless legs syndrome in patients taking neuroleptic drugs. J Neurol Sci. 2012;314(1–2):158–60.

    Article  PubMed  Google Scholar 

  44. van Mill JG, Vogelzangs N, van Someren EJ, Hoogendijk WJ, Penninx BW. Sleep duration, but not insomnia, predicts the 2-year course of depressive and anxiety disorders. J Clin Psychiatry. 2014;75(2):119–26.

    Article  PubMed  Google Scholar 

  45. Paykel ES. Basic concepts of depression. Dialogues Clin Neurosci. 2008;10(3):279–89.

    PubMed  PubMed Central  Google Scholar 

  46. Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, Felt BT, et al. Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain: J Neurol. 2009;132(Pt 9):2403–12.

    Article  Google Scholar 

  47. Cervenka S, Palhagen SE, Comley RA, Panagiotidis G, Cselenyi Z, Matthews JC, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain: J Neurol. 2006;129(Pt 8):2017–28.

    Article  Google Scholar 

  48. Bennabi D, Vandel P, Papaxanthis C, Pozzo T, Haffen E. Psychomotor retardation in depression: a systematic review of diagnostic, pathophysiologic, and therapeutic implications. BioMed Res Int. 2013;2013:158746.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Brennan BP, Rauch SL, Jensen JE, Pope HG Jr. A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol Psychiatry. 2013;73(1):24–31.

    Article  PubMed  Google Scholar 

  50. Nikolaus S, Antke C, Beu M, Muller HW. Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders-results from in vivo imaging studies. Rev Neurosci. 2010;21(2):119–39.

    Article  CAS  PubMed  Google Scholar 

  51. Pearson VE, Allen RP, Dean T, Gamaldo CE, Lesage SR, Earley CJ. Cognitive deficits associated with restless legs syndrome (RLS). Sleep Med. 2006;7(1):25–30.

    Article  PubMed  Google Scholar 

  52. Fulda S, Beitinger ME, Reppermund S, Winkelmann J, Wetter TC. Short-term attention and verbal fluency is decreased in restless legs syndrome patients. Mov Disord (Official Journal Movement Disorder Society). 2010;25(15):2641–8.

    Article  Google Scholar 

  53. Gamaldo CE, Benbrook AR, Allen RP, Oguntimein O, Earley CJ. A further evaluation of the cognitive deficits associated with restless legs syndrome (RLS). Sleep Med. 2008;9(5):500–5.

    Article  PubMed  Google Scholar 

  54. Driver-Dunckley E, Connor D, Hentz J. No evidence for cognitive dysfunction or depression in patients with mild restless legs syndrome. Mov Disord (Official Journal Movement Disorder Society). 2009;24:1843–7.

    Article  Google Scholar 

  55. Lee HB, Ramsey CM, Spira AP, Vachon J, Allen R, Munro CA. Comparison of cognitive functioning among individuals with treated restless legs syndrome (RLS), untreated RLS, and no RLS. J Neuropsychiatry Clin Neurosci. 2014;26(1):87–91.

    Article  PubMed  Google Scholar 

  56. Cortese S, Konofal E, Lecendreux M, Arnulf I, Mouren MC, Darra F, et al. Restless legs syndrome and attention-deficit/hyperactivity disorder: a review of the literature. Sleep. 2005;28(8):1007–13.

    Article  PubMed  Google Scholar 

  57. Chervin R, Archbold K, Dillon J, Pituch K, Panahi P, Dahl R, et al. Associations between symptoms of inattention, hyperactivity, restlessness legs, and periodic leg movements. Sleep. 2002;25(2):213–8.

    PubMed  Google Scholar 

  58. Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L. Restless legs syndrome: prevalence and impact in children and adolescents—the Peds REST study. Pediatrics. 2007;120(2):253–66.

    Article  PubMed  Google Scholar 

  59. Wagner ML, Walters AS, Fisher BC. Symptoms of attention-deficit/hyperactivity disorder in adults with restless legs syndrome. Sleep. 2004;27(8):1499–504.

    Article  PubMed  Google Scholar 

  60. England SJ, Picchietti DL, Couvadelli BV, Fisher BC, Siddiqui F, Wagner ML, et al. L-dopa improves restless legs syndrome and periodic limb movements in sleep but not attention-deficit-hyperactivity disorder in a double-blind trial in children. Sleep Med. 2011;12(5):471–7.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Bienvenu OJ, Samuels JF, Costa PT, Reti IM, Eaton WW, Nestadt G. Anxiety and depressive disorders and the five-factor model of personality: a higher- and lower-order personality trait investigation in a community sample. Depress Anxiety. 2004;20(2):92–7.

    Article  PubMed  Google Scholar 

  62. Kalaydjian A, Bienvenu OJ, Hening WA, Allen RP, Eaton WW, Lee HB. Restless legs syndrome and the five-factor model of personality: results from a community sample. Sleep Med. 2009;10(6):672–5.

    Article  CAS  PubMed  Google Scholar 

  63. Steinig J, Reess G, Klösch C, Sauter J, Zeitlhofer, Happe S. Personality traits in patients with restless legs syndrome. Somnologie-Schlafforschung und Schlafmedizin. 2013;17(4):281–3.

    Google Scholar 

  64. Ferini-Strambi L, Walters AS, Sica D. The relationship among restless legs syndrome (Willis-Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease. J Neurol. 2013.

    Google Scholar 

  65. Perez-Lloret S, Rey MV, Bondon-Guitton E, Rascol O, Montastruc AJ. French Association of Regional Pharmacovigilance C. Drugs associated with restless legs syndrome: a case/noncase study in the French Pharmacovigilance Database. J Clin Psychopharmacol. 2012;32(6):824–7.

    Article  CAS  PubMed  Google Scholar 

  66. Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64(3):327–37.

    Article  CAS  PubMed  Google Scholar 

  67. Montplaisir J, Lorrain D, Godbout R. Restless legs syndrome and periodic leg movements in sleep: the primary role of dopaminergic mechanism. Eur Neurol. 1991;31(1):41–3.

    Article  CAS  PubMed  Google Scholar 

  68. Garvey MJ, Tollefson GD. Occurrence of myoclonus in patients treated with cyclic antidepressants. Arch Gen Psychiatry. 1987;44(3):269–72.

    Article  CAS  PubMed  Google Scholar 

  69. Yang C, White DP, Winkelman JW. Antidepressants and periodic leg movements of sleep. Biol Psychiatry. 2005;58(6):510–4.

    Article  CAS  PubMed  Google Scholar 

  70. Winkelman JW, James L. Serotonergic antidepressants are associated with REM sleep without atonia. Sleep. 2004;27(2):317–21.

    Article  PubMed  Google Scholar 

  71. Bakshi R. Fluoxetine and restless legs syndrome. J Neurol Sci. 1996;142(1–2):151–2.

    Article  CAS  PubMed  Google Scholar 

  72. Sanz-Fuentenebro FJ, Huidobro A, Tejadas-Rivas A. Restless legs syndrome and paroxetine. Acta Psychiatr Scand. 1996;94(6):482–4.

    Article  CAS  PubMed  Google Scholar 

  73. Perroud N, Lazignac C, Baleydier B, Cicotti A, Maris S, Damsa C. Restless legs syndrome induced by citalopram: a psychiatric emergency? Gen Hosp Psychiatry. 2007;29(1):72–4.

    Article  PubMed  Google Scholar 

  74. Hargrave R, Beckley DJ. Restless leg syndrome exacerbated by sertraline. Psychosomatics. 1998;39(2):177–8.

    Article  CAS  PubMed  Google Scholar 

  75. Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry. 1997;58(8):348–50.

    Article  CAS  PubMed  Google Scholar 

  76. Page RL 2nd, Ruscin JM, Bainbridge JL, Brieke AA. Restless legs syndrome induced by escitalopram: case report and review of the literature. Pharmacotherapy. 2008;28(2):271–80.

    Article  CAS  PubMed  Google Scholar 

  77. Chou KJ, Chen PY, Huang MC. Restless legs syndrome following the combined use of quetiapine and paroxetine. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(6):1139–40.

    Article  PubMed  Google Scholar 

  78. Damsa C, Bumb A, Bianchi-Demicheli F, Vidailhet P, Sterck R, Andreoli A, et al. “Dopamine-dependent” side effects of selective serotonin reuptake inhibitors: a clinical review. J Clin Psychiatry. 2004;65(8):1064–8.

    Article  CAS  PubMed  Google Scholar 

  79. Belli H, Akbudak M, Ural C. Duloxetine-related galactorrhea and restless legs syndrome: a case report. Psychiatria Danubina. 2013;25(3):266–7.

    PubMed  Google Scholar 

  80. Michopoulos I, Ferentinos P, Oulis P, Gournellis R. Restless legs syndrome associated with the combined use of quetiapine and venlafaxine. J Clin Psychopharmacol. 2014;34(1):159–61.

    Article  PubMed  Google Scholar 

  81. Brown EE, Nomikos GG, Wilson C, Fibiger HC. Chronic desipramine enhances the effect of locally applied amphetamine on interstitial concentrations of dopamine in the nucleus accumbens. Eur J Pharmacol. 1991;202(1):125–7.

    Article  CAS  PubMed  Google Scholar 

  82. Scavone C, Aizenstein ML, Planeta Cda S, De Lucia R. Long-term effects of imipramine on striatal dopamine autoreceptor function: involvement of both noradrenergic and serotonergic systems. Gen Pharmacol. 1992;23(3):397–401.

    Article  CAS  PubMed  Google Scholar 

  83. Mago R, Mahajan R, Thase ME. Levomilnacipran: a newly approved drug for treatment of major depressive disorder. Expert Rev Clin Pharmacol. 2014;7(2):137–45.

    Article  CAS  PubMed  Google Scholar 

  84. Dimmitt SB, Riley GJ. Selective serotonin receptor uptake inhibitors can reduce restless legs symptoms. Arch Intern Med. 2000;160(5):712.

    Article  CAS  PubMed  Google Scholar 

  85. Brown LK, Dedrick DL, Doggett JW, Guido PS. Antidepressant medication use and restless legs syndrome in patients presenting with insomnia. Sleep Med. 2005;6(5):443–50.

    Article  PubMed  Google Scholar 

  86. Shioda K, Nisijima K, Yamauchi Y, Ohtuka K, Kato S. Use of a serotonin 1A receptor agonist to treat restless legs syndrome. J Clin Psychopharmacol. 2006;26(6):673–5.

    Article  PubMed  Google Scholar 

  87. Bahk WM, Pae CU, Chae JH, Jun TY, Kim KS. Mirtazapine may have the propensity for developing a restless legs syndrome? A case report. Psychiatry Clin Neurosci. 2002;56(2):209–10.

    Article  PubMed  Google Scholar 

  88. Teive HA, de Quadros A, Barros FC, Werneck LC. Worsening of autosomal dominant restless legs syndrome after use of mirtazapine: case report. Arq Neuropsiquiatr. 2002;60(4):1025–9.

    Article  PubMed  Google Scholar 

  89. Agargun MY, Kara H, Ozbek H, Tombul T, Ozer OA. Restless legs syndrome induced by mirtazapine. Journal Clin Psychiatry. 2002;63(12):1179.

    Article  Google Scholar 

  90. Bonin B, Vandel P, Kantelip JP. Mirtazapine and restless leg syndrome: a case report. Therapie. 2000;55(5):655–6.

    CAS  PubMed  Google Scholar 

  91. Kim SW, Shin IS, Kim JM, Park KH, Youn T, Yoon JS. Factors potentiating the risk of mirtazapine-associated restless legs syndrome. Hum Psychopharmacol. 2008;23(7):615–20.

    Article  PubMed  Google Scholar 

  92. Bayard M, Bailey B, Acharya D, Ambreen F, Duggal S, Kaur T, et al. Bupropion and restless legs syndrome: a randomized controlled trial. J Am Board Family Med: JABFM. 2011;24(4):422–8.

    Article  PubMed  Google Scholar 

  93. Park YM, Lee HJ, Kang SG, Cho JH, Kim L. Resolution of pregabalin and mirtazapine associated restless legs syndrome by bupropion in a patient with major depressive disorder. Psychiatry Inv. 2009;6(4):313–5.

    Article  Google Scholar 

  94. Lee JJ, Erdos J, Wilkosz MF, LaPlante R, Wagoner B. Bupropion as a possible treatment option for restless legs syndrome. Ann Pharmacother. 2009;43(2):370–4.

    Article  CAS  PubMed  Google Scholar 

  95. Kim SW, Shin IS, Kim JM, Yang SJ, Shin HY, Yoon JS. Bupropion may improve restless legs syndrome: a report of three cases. Clin Neuropharmacol. 2005;28(6):298–301.

    Article  PubMed  Google Scholar 

  96. Nofzinger EA, Fasiczka A, Berman S, Thase ME. Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. J Clin Psychiatry. 2000;61(11):858–62.

    Article  CAS  PubMed  Google Scholar 

  97. Feighner JP, Meredith CH, Stern WC, Hendrickson G, Miller LL. A double-blind study of bupropion and placebo in depression. Am J Psychiatry. 1984;141(4):525–9.

    Article  CAS  PubMed  Google Scholar 

  98. Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P, Gruber G, Mandl M, Strobl R, et al. Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(2):249–60.

    Article  CAS  PubMed  Google Scholar 

  99. Saletu M, Anderer P, Saletu-Zyhlarz G, Prause W, Semler B, Zoghlami A, et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol: J Eur Coll Neuropsychopharmacol. 2001;11(2):153–61.

    Article  CAS  Google Scholar 

  100. Bezerra ML, Martinez JV. Zolpidem in restless legs syndrome. Eur Neurol. 2002;48(3):180–1.

    Article  CAS  PubMed  Google Scholar 

  101. Allen R, Lesage S, Earley C. Anti-histamines and benzodiazepines exacerbate daytime restless legs syndrome symptoms. Sleep. 2005;28:A279.

    Google Scholar 

  102. Di Fabio R, Casali C, Vadala R, Pierelli F. Hydroxyzine hydrochloride in familial restless legs syndrome. Can J Neurol Sci Le Journal canadien des sciences neurologiques. 2010;37(3):406–7.

    Article  Google Scholar 

  103. Horiguchi J, Yamashita H, Mizuno S, Kuramoto Y, Kagaya A, Yamawaki S, et al. Nocturnal eating/drinking syndrome and neuroleptic-induced restless legs syndrome. Int Clin Psychopharmacol. 1999;14(1):33–6.

    CAS  PubMed  Google Scholar 

  104. Wetter TC, Brunner J, Bronisch T. Restless legs syndrome probably induced by risperidone treatment. Pharmacopsychiatry. 2002;35(3):109–11.

    Article  CAS  PubMed  Google Scholar 

  105. Kraus T, Schuld A, Pollmacher T. Periodic leg movements in sleep and restless legs syndrome probably caused by olanzapine. J Clin Psychopharmacol. 1999;19(5):478–9.

    Article  CAS  PubMed  Google Scholar 

  106. Kang SG, Lee HJ, Kim L. Restless legs syndrome and periodic limb movements during sleep probably associated with olanzapine. J Psychopharmacol. 2009;23(5):597–601.

    Article  CAS  PubMed  Google Scholar 

  107. Khalid I, Rana L, Khalid TJ, Roehrs T. Refractory restless legs syndrome likely caused by olanzapine. J Clin Sleep Med: JCSM (Official Publication of the American Academy of Sleep Medicine). 2009;5(1):68–9.

    Google Scholar 

  108. Pinninti NR, Mago R, Townsend J, Doghramji K. Periodic restless legs syndrome associated with quetiapine use: a case report. J Clin Psychopharmacol. 2005;25(6):617–8.

    Article  PubMed  Google Scholar 

  109. Urbano MR, Ware JC. Restless legs syndrome caused by quetiapine successfully treated with ropinirole in 2 patients with bipolar disorder. J Clin Psychopharmacol. 2008;28(6):704–5.

    Article  PubMed  Google Scholar 

  110. Rittmannsberger H, Werl R. Restless legs syndrome induced by quetiapine: report of seven cases and review of the literature. Int J Neuropsychopharmacol (Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum). 2013;16(6):1427–31.

    Article  CAS  Google Scholar 

  111. Webb J. Co-occurring akathisia and restless legs syndrome likely induced by quetiapine. J Neuropsychiatry Clin Neurosci. 2012;24(2):E46–7.

    PubMed  Google Scholar 

  112. Duggal HS, Mendhekar DN. Clozapine-associated restless legs syndrome. J Clin Psychopharmacol. 2007;27(1):89–90.

    Article  PubMed  Google Scholar 

  113. Desautels A, Turecki G, Montplaisir J, Ftouhi-Paquin N, Michaud M, Chouinard VA, et al. Dopaminergic neurotransmission and restless legs syndrome: a genetic association analysis. Neurology. 2001;57(7):1304–6.

    Article  CAS  PubMed  Google Scholar 

  114. Kang SG, Lee HJ, Choi JE, Park YM, Park JH, Han C, et al. Association study between antipsychotics- induced restless legs syndrome and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in schizophrenia. Neuropsychobiology. 2008;57(1–2):49–54.

    Article  CAS  PubMed  Google Scholar 

  115. Kang SG, Park YM, Choi JE, Lim SW, Lee HJ, Lee SH, et al. Association study between antipsychotic-induced restless legs syndrome and polymorphisms of monoamine oxidase genes in schizophrenia. Hum Psychopharmacol. 2010;25(5):397–403.

    Article  CAS  PubMed  Google Scholar 

  116. Kang SG, Lee HJ, Park YM, Yang HJ, Song HM, Lee YJ, et al. The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia. Hum Psychopharmacol. 2013;28(2):117–23.

    Article  CAS  PubMed  Google Scholar 

  117. Raveendranathan D, Shiva L, Venkatasubramanian G, Rao MG, Varambally S, Gangadhar BN. Clozapine-induced restless legs syndrome treated with aripiprazole. J Neuropsychiatry Clin Neurosci. 2013;25(2):E62–3.

    Article  PubMed  Google Scholar 

  118. Virit O, Selek S, Savas HA, Kokacya H. Improvement of restless legs syndrome and trichotillomania with aripiprazole. J Clin Pharm Ther. 2009;34(6):723–5.

    Article  CAS  PubMed  Google Scholar 

  119. Kikukawa S. Effectiveness of aripiprazole in treatment of adults with attention deficit disorder and restless legs syndrome. Int J Neuropsychopharmacol (Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum). 2008;11(3):439–40.

    CAS  Google Scholar 

  120. McLean AJ. The use of the dopamine-receptor partial agonist aripiprazole in the treatment of restless legs syndrome. Sleep. 2004;27(5):1022.

    PubMed  Google Scholar 

  121. Bolanos-Vergaray J, Obaya JC, Gonzalez R, Echeverri C, Piquer P. Restless legs syndrome due to aripiprazole. Eur J Clin Pharmacol. 2011;67(5):539–40.

    Article  PubMed  Google Scholar 

  122. Sullivan MA, Wilbur R. Gabapentin pharmacotherapy for antipsychotic-induced akathisia: single-patient experiment and case report. Ther Adv Psychopharmacol. 2014;4(2):100–2.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Telstad W, Sorensen O, Larsen S, Lillevold PE, Stensrud P, Nyberg-Hansen R. Treatment of the restless legs syndrome with carbamazepine: a double blind study. Br Med J. 1984;288(6415):444–6.

    Article  CAS  Google Scholar 

  124. Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002;59(10):1573–9.

    Article  CAS  PubMed  Google Scholar 

  125. Eisensehr I, Ehrenberg BL, Rogge Solti S, Noachtar S. Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic acid compared with slow-release levodopa/benserazid. J Neurol. 2004;251(5):579–83.

    Article  CAS  PubMed  Google Scholar 

  126. McMeekin H. Treatment of bipolar disorder, restless legs syndrome and parkinsonian symptoms using lamotrigine: a report of seven patients. J South Carolina Med Assoc. 2007;103(3):69–73.

    Google Scholar 

  127. Terao T, Terao M, Yoshimura R, Abe K. Restless legs syndrome induced by lithium. Biol Psychiatry. 1991;30(11):1167–70.

    Article  CAS  PubMed  Google Scholar 

  128. Evidente VG, Caviness JN. Focal cortical transient preceding myoclonus during lithium and tricyclic antidepressant therapy. Neurology. 1999;52(1):211–3.

    Article  CAS  PubMed  Google Scholar 

  129. Heiman EM, Christie M. Lithium-aggravated nocturnal myoclonus and restless legs syndrome. Am J Psychiatry. 1986;143(9):1191–2.

    CAS  PubMed  Google Scholar 

  130. Driver-Dunckley ED, Noble BN, Hentz JG, Evidente VG, Caviness JN, Parish J, et al. Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome. Clin Neuropharmacol. 2007;30(5):249–55.

    Article  CAS  PubMed  Google Scholar 

  131. Quickfall J, Suchowersky O. Pathological gambling associated with dopamine agonist use in restless legs syndrome. Parkinsonism Related Disord. 2007;13(8):535–6.

    Article  Google Scholar 

  132. Tippmann-Peikert M, Park JG, Boeve BF, Shepard JW, Silber MH. Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists. Neurology. 2007;68(4):301–3.

    Article  CAS  PubMed  Google Scholar 

  133. Salas RE, Allen RP, Earley CJ, Gamaldo CE. Drug hoarding: a case of atypical dopamine dysregulation syndrome in a RLS patient. Mov Disord (Official Journal of the Movement Disorder Society). 2009;24(4):627–8.

    Article  Google Scholar 

  134. Pourcher E, Remillard S, Cohen H. Compulsive habits in restless legs syndrome patients under dopaminergic treatment. J Neurol Sci. 2010;290(1–2):52–6.

    Article  CAS  PubMed  Google Scholar 

  135. Evans AH, Stegeman JR. Punding in patients on dopamine agonists for restless leg syndrome. Mov Disord (Official Journal Movement Disorder Society). 2009;24(1):140–1.

    Article  Google Scholar 

  136. 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 (Official Journal of the Movement Disorder Society). 2009;24(6):871–7.

    Article  Google Scholar 

  137. Arora A, Fletcher P. Parkinsonism hyperpyrexia syndrome caused by abrupt withdrawal of ropinirole. Br J Hosp Med. 2013;74(12):698–9.

    Article  Google Scholar 

  138. Wensel TM, Powe KW, Cates ME. Pregabalin for the treatment of generalized anxiety disorder. Ann Pharmacotherapy. 2012;46(3):424–9.

    Article  CAS  Google Scholar 

  139. Boschen MJ. A meta-analysis of the efficacy of pregabalin in the treatment of generalized anxiety disorder. Can J Psychiatry Revue canadienne de psychiatrie. 2011;56(9):558–66.

    Article  PubMed  Google Scholar 

  140. Gahr M, Freudenmann RW, Hiemke C, Kolle MA, Schonfeldt-Lecuona C. Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol. 2013;69(6):1335–42.

    Article  PubMed  Google Scholar 

  141. Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Hogl B, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013;14(7):675–84.

    Article  PubMed  Google Scholar 

  142. Benes H, Mattern W, Peglau I, Dreykluft T, Bergmann L, Hansen C, et al. Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study. J Neurol. 2011;258(6):1046–54.

    Article  PubMed  Google Scholar 

  143. Montagna P, Hornyak M, Ulfberg J, Hong SB, Koester J, Crespi G, et al. Randomized trial of pramipexole for patients with restless legs syndrome (RLS) and RLS-related impairment of mood. Sleep Med. 2011;12(1):34–40.

    Article  PubMed  Google Scholar 

  144. Pae CU. Pramipexole augmentation in treatment-resistant major depressive disorder. Expert Rev Neurother. 2014;14(1):5–8.

    Article  CAS  PubMed  Google Scholar 

  145. Hornyak M. Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management. CNS Drugs. 2010;24(2):89–98.

    Article  PubMed  Google Scholar 

  146. Singh A, Althoff R, Martineau RJ, Jacobson J. Pramipexole, ropinirole, and mania in Parkinson’s disease. Am J Psychiatry. 2005;162(4):814–5.

    Article  PubMed  Google Scholar 

  147. Kelleher JP, Centorrino F, Huxley NA, Bates JA, Drake JK, Egli S, et al. Pilot randomized, controlled trial of pramipexole to augment antipsychotic treatment. Eur Neuropsychopharmacol (The Journal of the European College of Neuropsychopharmacology). 2012;22(6):415–8.

    Article  CAS  Google Scholar 

  148. Michalopoulou PG, Azim A, Tracy D, Shergill SS. Ropinirole as an effective adjunctive treatment for clozapine-resistant negative symptoms in simple schizophrenia: a case report. J Clin Psychopharmacol. 2012;32(5):719–20.

    Article  PubMed  Google Scholar 

  149. Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ. The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”). Sleep Med. 2009;10(9):976–81.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Ondo WG. Common comorbidities and differential diagnosis of restless legs syndrome. J Clin Psychiatry. 2014;75(3):e06.

    Article  PubMed  Google Scholar 

  151. Ferini-Strambi L. RLS-like symptoms: differential diagnosis by history and clinical assessment. Sleep Med. 2007;8(Suppl 2):S3–6.

    Article  PubMed  Google Scholar 

  152. Benes H, Walters AS, Allen RP, Hening WA, Kohnen R. Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics. Mov Disord (Official Journal of the Movement Disorder Society). 2007;22(Suppl 18):S401–8.

    Article  Google Scholar 

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Oldham, M.A., Lee, H.B. (2017). Mental Health Disorders Associated with RLS. In: Manconi, M., GarcĂ­a-Borreguero, D. (eds) Restless Legs Syndrome/Willis Ekbom Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6777-3_2

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