CNS Drugs

, Volume 26, Issue 2, pp 135–153

The Role of Antipsychotics in the Management of Fibromyalgia

Review Article


Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2–4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the α2δ ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (nor-epinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease.

First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and amisulpride, have demonstrated antidepressant activity, with quetiapine approved for the treatment of bipolar depression and refractory major depression, and aripiprazole approved as an adjunctive treatment for major depressive disorder. Finally, several old and new antipsychotics, including promethazine, levopromazine, olanzapine, quetiapine and ziprasidone, have been shown to improve sleep parameters in healthy subjects. Each of these properties suggests that antipsychotics could represent a new potential alternative for the treatment of fibromyalgia syndrome.

To date, most of the published studies on the use of antipsychotics in the treatment of fibromyalgia syndrome have been uncontrolled, either case reports or case series, dealing with olanzapine, quetiapine, ziprasidone, levopromazine and amisulpride. The studies on olanzapine and quetiapine have suggested therapeutic efficacy although, in the case of olanzapine, hampered by tolerability problems. A double-blind controlled trial, published in 1980, showed that chlorpromazine increased slow-wave sleep and improved pain and mood disturbances. More recently, four double-blind controlled studies have explored the efficacy of quetiapine, either alone or as an add-on treatment, in fibromyalgia management. None of these trials has yet been published, although two of them have been presented as congress communications, both of them suggesting that quetiapine could be a potential alternative treatment for fibromyalgia.

In summary, the current available evidence suggests that at least some antipsychotics, specifically quetiapine, could be useful for the treatment of fibromyalgia and that further studies on the efficacy of these compounds are worth pursuing.


  1. 1.
    Inanci F, Yunus MB. History of fibromyalgia: past to present. Curr Pain Headache Rep 2004 Oct; 8(5): 369–78CrossRefGoogle Scholar
  2. 2.
    Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum 1990; 33: 160–72PubMedCrossRefGoogle Scholar
  3. 3.
    World Health Organization. FAQ on ICD: is fibromyalgia included in the International Classification of Diseases [online]? Available from URL: [Accessed 2011 Jul4]
  4. 4.
    Wolfe F. New American College of Rheumatology criteria for fibromyalgia: a twenty-year journey. Arthritis Care Res 2010 May; 62(5): 583–4CrossRefGoogle Scholar
  5. 5.
    Nielsen LA, Henriksson KG. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization. Best Pract Clin Res Rheumatol 2007 Jun; 21(3): 465–80CrossRefGoogle Scholar
  6. 6.
    Arnold LM, Clauw DJ, McCarberg DH, et al. Improving the recognition and diagnosis of fibromyalgia. Mayo Clin Proc 2011 May; 86(5): 457–64PubMedCrossRefGoogle Scholar
  7. 7.
    Wolfe F, Claw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 2010 May; 62(5): 600–10CrossRefGoogle Scholar
  8. 8.
    Moldofsky H. The significance, assessment, and management of nonrestorative sleep in fibromyalgia syndrome. CNS Spectrums 2008 Mar; 13 (3 Suppl. 5): 22–6PubMedGoogle Scholar
  9. 9.
    Moldofsky H, Lue FA. The relationship of alpha and delta EEG frequencies to pain and mood in ‘fibrositis’ patients treated with chlorpromazine and L-tryptophan. Electroencephalogr Clin Neurophysiol 1980 Oct; 50(1–2): 71–80PubMedGoogle Scholar
  10. 10.
    Branco JC, Martin A, Paiva C. Treatment of sleep abnormalities and clinical complaints in fibromyalgia with trazodone [abstract]. Arthritis Rheum 1996; 39: S91Google Scholar
  11. 11.
    Morillas-Arques P, Rodriguez-Lopez CM, Molina-Barea R, et al. Trazodone for the treatment of fibromyalgia: an open-label, 12-week study. BMC Musculoskelet Disord 2010 Sept 10; 11: 24CrossRefGoogle Scholar
  12. 12.
    Moldofsky H, Inhaber NH, Guinta DR, et al. Effects of sodium oxybate on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study. J Rheumatol 2010 Oct; 37(10): 2156–66PubMedCrossRefGoogle Scholar
  13. 13.
    Hindmarch I, Dawson J, Stanley N. A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep 2005 Feb; 28(2): 187–93PubMedGoogle Scholar
  14. 14.
    Guymer EK, Clauw DJ. Treatment of fatigue in fibromyalgia. Rheum Clin Dis North Am 2002 May; 28(2): 367–78CrossRefGoogle Scholar
  15. 15.
    Finan PH, Zautra AJ. Fibromyalgia and fatigue: central processing, widespread dysfunction. PM R 2010 May; 2(5): 431–7PubMedCrossRefGoogle Scholar
  16. 16.
    Häuser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials. Arthritis Res Ther 2010; 12(3): R79PubMedCrossRefGoogle Scholar
  17. 17.
    Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995 Jan; 38(1): 19–28PubMedCrossRefGoogle Scholar
  18. 18.
    Farooqi A, Gibson T. Prevalence of the major rheumatic disorders in the adult population of North Pakistan. Br J Rheumatol 1998 May; 37(5): 491–5PubMedCrossRefGoogle Scholar
  19. 19.
    White KP, Speechley M, Harth M, et al. The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol 1999 Jul; 26(7): 1570–6PubMedGoogle Scholar
  20. 20.
    Senna ER, De Barros AL, Silva EO, et al. Prevalence of rheumatic diseases in Brazil: a study using the COPCORD approach. J Rheumatol 2004 Mar; 31(3): 594–7PubMedGoogle Scholar
  21. 21.
    Haq SA, Darmawan J, Islam MN, et al. Prevalence of rheumatic diseases and associated outcomes in rural and urban communities in Bangladesh: a COPCORD study. J Rheumatol 2005 Feb; 32(2): 348–53PubMedGoogle Scholar
  22. 22.
    Branco JC, Bannwarth B, Failde I, et al. Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum 2010 Jun; 39(6): 448–53PubMedCrossRefGoogle Scholar
  23. 23.
    Davatchi F, Jamshidi AR, Banihashemi AT, et al. WHO-ILAR COPCORD Study (Stage 1, Urban Study) in Iran. J Rheumatol 2008 Jul; 35(7): 1384–90PubMedGoogle Scholar
  24. 24.
    Reyes-Llerena GA, Guibert-Toledano M, Penedo-Coello A, et al. Community-based study to estimate prevalence and burden of illness of rheumatic diseases in Cuba: a COPCORD study. J Clin Rheumatol 2009 Mar; 15(2): 51–5PubMedCrossRefGoogle Scholar
  25. 25.
    Alvarez-Nemegyei J, Peláez-Ballestas I, Sanin LH, et al. Prevalence of musculoskeletal pain and rheumatic diseases in the southeastern region of Mexico: a COP-CORD-based community survey. J Rheumatol Suppl 2011 Jan; 86: 21–5PubMedCrossRefGoogle Scholar
  26. 26.
    Zeng QY, Zang CH, Lin L, et al. Epidemiologic study of soft tissue rheumatism in Shantou and Taiyuan, China. Chin Med J 2010 Aug 5; 123(15): 2058–62PubMedGoogle Scholar
  27. 27.
    Bradley LA. Pathophysiology of fibromyalgia. Am J Med 2002 Dec; 122 (12 Suppl.): S22–30CrossRefGoogle Scholar
  28. 28.
    Di Franco M, Iannucelli C, Valesini G. Neuroendocrine immunology of fibromyalgia. Ann N Y Acad Sci 2010 Apr; 1193: 84–90PubMedCrossRefGoogle Scholar
  29. 29.
    Staud R. Autonomic dysfunction in fibromyalgia syndrome: postural orthostatic tachycardia. Curr Rheumatol Rep 2008 Dec; 10(6): 463–6PubMedCrossRefGoogle Scholar
  30. 30.
    Wood PB, Holman AJ. An elephant among us: the role of dopamine in the pathophysiology of fibromyalgia. J Rheumatol 2009 Feb; 36(2): 221–4PubMedCrossRefGoogle Scholar
  31. 31.
    Al-Allaf AW, Dunbar KL, Hallum NS, et al. A case-control study examining the role of physical trauma in the onset of fibromyalgia syndrome. Rheumatology 2002 Apr; 41(4): 450–3PubMedCrossRefGoogle Scholar
  32. 32.
    Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmunity Rev 2008 Oct; 8(1): 41–3CrossRefGoogle Scholar
  33. 33.
    Häuser W, Kosseva M, Üceyler N, et al. Emotional, physical, and sexual abuse in fibromyalgia syndrome: a systematic review with meta-analysis. Arthritis Care Res 2011 Jun; 63(6): 808–20CrossRefGoogle Scholar
  34. 34.
    Van Houdenhove B, Egle UT. Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together. Psychother Psychosom 2004 Sep–Oct; 73(5): 267–75PubMedCrossRefGoogle Scholar
  35. 35.
    Lyon P, Cohen M, Quintner J. An evolutionary stress-response hypothesis for chronic widespread pain (fibromyalgia syndrome). Pain Med 2011 Aug; 12(8): 1167–78PubMedCrossRefGoogle Scholar
  36. 36.
    Martinez-Lavin M. Biology and therapy of fibromyalgia: stress, the stress response system, and fibromyalgia. Arthritis Res Ther 2007; 9(4): 216PubMedCrossRefGoogle Scholar
  37. 37.
    Yunus MB. Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin Arthritis Rheum 2008 Jun; 37(6): 339–52PubMedCrossRefGoogle Scholar
  38. 38.
    Schmidt-Wilcke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol 2011 Jul 19; 7(9): 518–27PubMedCrossRefGoogle Scholar
  39. 39.
    Wolfe F, Michaud K, Li T, et al. Chronic conditions and health problems in rheumatic diseases: comparisons with rheumatoid arthritis, noninflammatory rheumatic disorders, systemic lupus erytemathosus, and fibromyalgia. J Rheumatol 2010 Feb; 37(2): 305–15PubMedCrossRefGoogle Scholar
  40. 40.
    Weir PT, Harlan GA, Nkoy FL, et al. The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes. J Clin Rheumatol 2006 Jun; 12(3): 124–8PubMedCrossRefGoogle Scholar
  41. 41.
    Bennett RM, Jones J, Turk DC, et al. An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord 2007 Mar 9; 8: 27PubMedCrossRefGoogle Scholar
  42. 42.
    Bennett RM, Friend R, Jones KD, et al. The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties. Arthritis Res Ther 2009; 11(4): R120PubMedCrossRefGoogle Scholar
  43. 43.
    Häuser W, Schmutzer G, Brähler E, et al. A cluster within the continuum of biopsychosocial distress can be labeled ‘fibromyalgia syndrome’: evidence from a representative German population survey. J Rheumatol 2009 Dec; 36(12): 2806–12PubMedCrossRefGoogle Scholar
  44. 44.
    Wolfe F, Michaud K. Outcome and predictor relationships in fibromyalgia and rheumatoid arthritis: evidence concerning the continuum versus discrete disorder hypothesis. J Rheumatol 2009 Apr; 36(4): 831–6PubMedCrossRefGoogle Scholar
  45. 45.
    Smith HS, Barkin RL. Fibromyalgia syndrome: a discussion of the syndrome and pharmacotherapy. Dis Month 2011 May; 57(5): 248–85CrossRefGoogle Scholar
  46. 46.
    Hassett AL, Gevirtz RN. Nonpharmacologic treatment for fibromyalgia: patient education, cognitive-behavioral therapy, relaxation techniques, and complementary and alternative medicine. Rheum Dis Clin North Am 2009 May; 35(2): 393–407PubMedCrossRefGoogle Scholar
  47. 47.
    Bennett R, Nelson D. Cognitive behavioral therapy for fibromyalgia. Nat Clin Pract Rheumatol 2006 Aug; 2(8): 416–24PubMedCrossRefGoogle Scholar
  48. 48.
    van Koulil S, Effting M, Kraaimaat FW, et al. Cognitive-behavioural therapies and exercise programmes for patients with fibromyalgia: state of the art and future directions. Ann Rheum Dis 2007 May; 66(5): 571–81PubMedCrossRefGoogle Scholar
  49. 49.
    Thieme K, Gracely RH. Are psychological treatments effective for fibromyalgia pain? Curr Rheumatol Rep 2009 Dec; 11(6): 443–50PubMedCrossRefGoogle Scholar
  50. 50.
    Glombiewski JA, Sawyer AT, Gutermann J, et al. Psychological treatments for fibromyalgia: a meta-analysis. Pain 2010 Nov; 151(2): 280–95PubMedCrossRefGoogle Scholar
  51. 51.
    Langhorst J, Klose P, Musial F, et al. Efficacy of acupuncture in fibromyalgia syndrome: a systematic review with a meta-analysis of controlled clinical trials. Rheumatology (Oxford) 2010 Apr; 49(4): 778–88CrossRefGoogle Scholar
  52. 52.
    Terry R, Perry R, Ernst E. An overview of systematic reviews of complementary and alternative medicine for fibromyalgia. Clin Rheumatol. Epub 2011 May 26Google Scholar
  53. 53.
    De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology (Oxford) 2010 Jun; 49(6): 1063–8CrossRefGoogle Scholar
  54. 54.
    Carville SF, Arendt-Nielsen S, Bliddal H, et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis 2008 Apr; 67(4): 536–41PubMedCrossRefGoogle Scholar
  55. 55.
    Häuser W, Bernardy K, Üçeyler N, et al. Treatment of fibromyalgia syndrome with gabapentin and pregabalin: a meta-analysis of randomized controlled trials. Pain 2009 Sep; 145(1–2): 69–81PubMedCrossRefGoogle Scholar
  56. 56.
    Bockbrader HN, Wesche D, Miller R, et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet 2010 Oct; 49(10): 661–9PubMedCrossRefGoogle Scholar
  57. 57.
    Verdu B, Decosterd I, Buclin T, et al. Antidepressants for the treatment of chronic pain. Drugs 2008; 68(18): 2611–32PubMedCrossRefGoogle Scholar
  58. 58.
    Häuser W, Bernardy K, Üçeyler N, et al. Treatment of fibromyalgia syndrome with antidepressants: a metaanalysis. JAMA 2009 Jan; 301(2): 198–209PubMedCrossRefGoogle Scholar
  59. 59.
    Häuser W, Petzke F, Üçeyler N, et al. Comparative efficacy and acceptability of amitriptyline, duloxetine and milna-cipran in fibromyalgia syndrome: a systematic review with meta-analysis. Rheumatology 2011 Mar; 50(3): 532–43PubMedCrossRefGoogle Scholar
  60. 60.
    Tofferi JK, Jackson JL, O’Malley PG. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis Rheum 2004 Feb; 51(1): 9–13PubMedCrossRefGoogle Scholar
  61. 61.
    Choy EH, Mease PJ, Kajdasz DK, et al. Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials. Clin Rheumatol 2009 Sep; 28(9): 1035–44PubMedCrossRefGoogle Scholar
  62. 62.
    Chwieduk CM, McCormack PL. Milnacipran in fibromyalgia. Drugs 2010; 70(1): 99–108PubMedCrossRefGoogle Scholar
  63. 63.
    Chappell AS, Littlejohn G, Kajdasz DK, et al. A 1-year safety and efficacy study of duloxetine in patients with fibromyalgia. Clin J Pain 2009 Jun; 25(5): 365–75PubMedCrossRefGoogle Scholar
  64. 64.
    Branco JC, Cherin P, Montagne A, et al. Longterm therapeutic response to milnacipran treatment for fibromyalgia: a European 1-year extension study following a 3-month study. J Rheumatol 2011 Jul; 38(7): 1403–12PubMedCrossRefGoogle Scholar
  65. 65.
    Späth M, Stratz T, Färber L, et al. Treatment of fibromyalgia with tropisetron: dose and efficacy correlations. Scand J Rheumatol Suppl 2004; 119: 63–6PubMedCrossRefGoogle Scholar
  66. 66.
    Vergne-Salle P, Dufauret-Lombard C, Bonnet C, et al. A randomised, double-blind, placebo-controlled trial of dolasetron, a 5-hydroxytryptamine 3 receptor antagonist, in patients with fibromyalgia. Eur J Pain 2011 May; 15(5): 509–14PubMedCrossRefGoogle Scholar
  67. 67.
    Holman AJ, Myers RR. A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum 2005 Aug; 52(8): 2495–505PubMedCrossRefGoogle Scholar
  68. 68.
    Russell IJ, Kamin M, Bennett RM, et al. Efficacy of tramadol in treatment of pain in fibromyalgia. J Clin Rheumatol 2000 Oct; 6(5): 250–7PubMedCrossRefGoogle Scholar
  69. 69.
    Bennett RM, Kamin M, Karim R, et al. Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med 2003 May; 114(7): 537–45PubMedCrossRefGoogle Scholar
  70. 70.
    Russell IJ, Holman AJ, Swick TJ, et al. Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study. Pain 2011 May; 152(5): 1007–17PubMedCrossRefGoogle Scholar
  71. 71.
    Staud R. Sodium oxybate for the treatment of fibromyalgia. Expert Opin Pharmacother 2011 Aug; 12(11): 1789–98PubMedGoogle Scholar
  72. 72.
    Felson DT, Goldenberg DL. The natural history of fibromyalgia. Arthritis Rheum 1986 Dec; 29(12): 1522–6PubMedCrossRefGoogle Scholar
  73. 73.
    Wolfe F, Anderson J, Harkness D, et al. Health status and disease severity in fibromyalgia: results of a six-center longitudinal study. Arthritis Rheum 1997 Sep; 40(9): 1571–9PubMedCrossRefGoogle Scholar
  74. 74.
    Baumgartner E, Finckh A, Cedraschi C, et al. A six year prospective study of a cohort of patients with fibromyalgia. Ann Rheum Dis 2002 Jul; 61(7): 644–5PubMedCrossRefGoogle Scholar
  75. 75.
    Nöller V, Sprott H. Prospective epidemiological observations on the course of the disease in fibromyalgia patients. J Negat Results Biomed 2003 Aug 23; 2: 4PubMedCrossRefGoogle Scholar
  76. 76.
    St John AB, Born CK. Characterization of analgesic and activity effects of methotrimeprazine and morphine. Res Commun Chem Pathol Pharmacol 1979 Oct; 26(1): 25–34PubMedGoogle Scholar
  77. 77.
    Gleeson RM, Atrens DM. Chlorpromazine hyperalgesia antagonizes clonidine analgesia but enhances morphine analgesia in rats tested in a hot-water tail-flick paradigm. Pyschopharmacology 1982; 78(2): 141–6CrossRefGoogle Scholar
  78. 78.
    Golbidi S, Moriuchi H, Irie T, et al. Involvement of calmodulin inhibition in analgesia induced with low doses of intrathecal trifluoperazine. Jpn J Pharmacol 2002 Feb; 88(2): 151–7PubMedCrossRefGoogle Scholar
  79. 79.
    Ghelardini C, Galeotti N, Uslenghi C, et al. Prochlorperazine induces central antinociception mediated by the muscarinic system. Pharmacol Res 2004 Sep; 50(3): 351–8PubMedCrossRefGoogle Scholar
  80. 80.
    Dong XW, Jia Y, Lu SX, et al. The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain. Psychopharmacology (Berl) 2007 Jan; 195(4): 559–68CrossRefGoogle Scholar
  81. 81.
    Chen YW, Chu CC, Chu KS, et al. Phenotiazine-type antipsychotics elicit cutaneous analgesia in rats. Acta Anaesthesiol Taiwan 2010 Mar; 48(1): 3–7PubMedCrossRefGoogle Scholar
  82. 82.
    Head M, Lal H, Puri S, et al. Enhancement of morphine analgesia after acute and chronic haloperidol. Life Sci 1979 May 28; 24(22): 2037–44PubMedCrossRefGoogle Scholar
  83. 83.
    Cendán CM, Pujalte JM, Portillo-Salido E, et al. Anti-nociceptive effects of haloperidol and its metabolites in the formalin test in mice. Psychopharmacology (Berl) 2005 Nov; 182(4): 485–93CrossRefGoogle Scholar
  84. 84.
    Entrena JM, Cobos EJ, Nieto FR, et al. Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors. Psychopharmacology 2009 Jul; 205(1): 21–33PubMedCrossRefGoogle Scholar
  85. 85.
    Schreiber S, Backer MM, Weizman R, et al. Augmentation of opioid-induced antinociception by the atypical anti-psychotic drug risperidone in mice. Neurosci Lett 1997 May 30; 228(1): 25–8PubMedCrossRefGoogle Scholar
  86. 86.
    DiPirro JM, Thompson AC, Suarez M, et al. Low doses of risperidone and morphine interact to produce more analgesia and greater extrapyramidal effects in rats. Neurosci Lett 2011 Feb 18; 490(1): 21–6PubMedCrossRefGoogle Scholar
  87. 87.
    Schreiber S, Getslev V, Backer MM, et al. The atypical neuroleptics clozapine and olanzapine differ regarding their antinociceptive mechanisms and potency. Pharmacol Biochem Behav 1999 Sep; 64(1): 75–80PubMedCrossRefGoogle Scholar
  88. 88.
    Weizman T, Pick CG, Backer MM, et al. The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms. Eur J Pharmacol 2003 Oct 8; 478(2–3): 155–9PubMedCrossRefGoogle Scholar
  89. 89.
    Kowalski J, Huzarska M, Jasinski R. Effect of fluphenazine on the footshock-induced opioid analgesia and leu-enkephalin concentration in the rat brain. Pol J Pharmacol Pharm 1988 Nov–Dec; 40(6): 621–5PubMedGoogle Scholar
  90. 90.
    Patt RB, Proper G, Reddy S. The neuroleptics as adjuvant analgesics. J Pain Symptom Manage 1994 Oct; 9(7): 446–53PubMedCrossRefGoogle Scholar
  91. 91.
    Robertson CE, Black DF, Swanson JW. Management of migraine headache in the emergency department. Semin Neurol 2010 Apr; 30(2): 201–11PubMedCrossRefGoogle Scholar
  92. 92.
    Pridmore S, Samilowitz H, Oberoi G. Will the atypical antipsychotics be analgesic? Australas Psychiatry 2003 March; 11(1): 59–61CrossRefGoogle Scholar
  93. 93.
    Fishbain DA, Cutler RB, Lewis J, et al. Do the second generation ‘atypical neuroleptics’ have analgesic properties? A structured evidence-based review. Pain Med 2004 Dec; 5(4): 359–65PubMedCrossRefGoogle Scholar
  94. 94.
    Seidel S, Aigner M, Ossege M, et al. Antipsychotics for acute and chronic pain in adults. Cochrane Database Syst Rev 2008 Oct 8; (4): CD004844Google Scholar
  95. 95.
    Seidel S, Aigner M, Ossege M, et al. Antipsychotics for acute and chronic pain in adults. J Pain Symptom Manage 2010 Apr; 39(4): 678–778CrossRefGoogle Scholar
  96. 96.
    Maina G, Vitalucci A, Gandolfo S, et al. Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study. J Clin Psychiatry 2002 Jan; 63(1): 38–43PubMedCrossRefGoogle Scholar
  97. 97.
    Bogetto F, Bonatto-Revello R, Ferro G, et al. Trattamento psicofarmacologico della burning mouth syndrome (BMS): studio su di un campioni de 121 pazienti. Minerva Psichiatrica 1999; 40(1): 1–10Google Scholar
  98. 98.
    Clavel M, Pommatau E. Analgesic effects of tiapride in man: a double-blind comparative clinical trial against placebo (author’s transl). Sem Hop 1980 Mar; 56(9–10): 430–3PubMedGoogle Scholar
  99. 99.
    Krymchantowski AV, Jevoux C, Moreira PF. An open pilot study assessing the benefits of quetiapine for the prevention of migraine refractory to the combination of atenolol, nortriptyline, and flunarizine. Pain Med 2010 Jan; 11(1): 48–52PubMedCrossRefGoogle Scholar
  100. 100.
    Arnold LM, Crofford LJ, Martin SA, et al. The effect of anxiety and depression on improvements in pain in a randomized, controlled trial of pregabalin for treatment of fibromyalgia. Pain Med 2007 Nov–Dec; 8(8): 633–8PubMedCrossRefGoogle Scholar
  101. 101.
    Jensen KB, Petzke F, Carville S, et al. Anxiety and depressive symptoms in fibromyalgia are related to poor perception of health but not to pain sensitivity or cerebral processing pain. Arthritis Rheum 2010 Nov; 62(11): 3488–95PubMedCrossRefGoogle Scholar
  102. 102.
    Wolfe F, Anderson J, Harkness D, et al. A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum 1997 Sep; 40(9): 1560–70PubMedCrossRefGoogle Scholar
  103. 103.
    Gao K, Gajwani P, Elhaj O, et al. Typical and atypical antipsychotics in bipolar depression. J Clin Psychiatry 2005 Nov; 66(11): 1376–85PubMedCrossRefGoogle Scholar
  104. 104.
    Gao K, Muzina D, Gajwani P, et al. Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review. J Clin Psychiatry 2006 Sept; 67(9): 1327–40PubMedCrossRefGoogle Scholar
  105. 105.
    Vulink NCC, Figee M, Denys D. Review of atypical antipsychotics in anxiety. Eur Neuropsychopharmacol 2011 Jun; 21(6): 429–49PubMedCrossRefGoogle Scholar
  106. 106.
    Lalonde CD, Van Lieshout RJ. Treating generalized anxiety disorder with second generation antipsychotics: a systematic review and metaanalysis. J Clin Psychopharmacol 2011 Jun; 31(3): 326–33PubMedCrossRefGoogle Scholar
  107. 107.
    Pies R. Should psychiatrists use atypical antipsychotics to treat nonpsychotic anxiety? Psychiatry 2009 Jun; 6(6): 29–37PubMedGoogle Scholar
  108. 108.
    Kukopulos A, Reginaldi D, Laddomada P, et al. Course of the manic-depressive cycle and changes caused by treatment. Pharmakopsychiatr Neuropsychopharmakol 1980 Jul; 13(4): 156–67PubMedGoogle Scholar
  109. 109.
    Harrow M, Yonan CA, Sands JR, et al. Depression in schizophrenia: are neuroleptics, akinesia or anhedonia involved? Schizophrenia Bull 1994; 20(2): 327–38CrossRefGoogle Scholar
  110. 110.
    DeBattista C, Hawkins J. Utility of atypical antipsychotics in the treatment of resistant unipolar depression. CNS Drugs 2009; 23(5): 369–77PubMedCrossRefGoogle Scholar
  111. 111.
    Cruz N, Sanchez-Moreno J, Torres F, et al. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol 2010 Feb; 13(1): 5–14PubMedCrossRefGoogle Scholar
  112. 112.
    Brugue E, Vieta E. Atypical antipsychotics in bipolar depression: neurobiological basis and clinical implications. Progr Neuropsychopharmacol Biol Psychiatry 2007 Jan 30; 31(1): 275–82CrossRefGoogle Scholar
  113. 113.
    Komossa K, Depping AM, Gaudchaud A, et al. Second-generation antipsychotics for major depressive disorder and dysthymia. Cochrane Database Syst Rev 2010 Dec 8; (12): CD008121Google Scholar
  114. 114.
    Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. CNS Drugs 2008; 22(11): 939–62PubMedCrossRefGoogle Scholar
  115. 115.
    Promethazine: prescribing information [online]. Available from URL: [Accessed 2011 May 15]
  116. 116.
    Nozinan®: product monograph [online]. Available from URL: [Accessed 2011 May 21]
  117. 117.
    Aukst-Margeti B, Margeti B, Tosi G, et al. Levomepromazine helps to reduce sleep problems in patients with PTSD. Eur Psychiatry 2004 Jun; 19(4): 235–6CrossRefGoogle Scholar
  118. 118.
    Sharpley AL, Vassallo CM, Cowen PJ. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT2C receptors in vivo. Biol Psychiatry 2000 Mar 1; 47(5): 468–70PubMedCrossRefGoogle Scholar
  119. 119.
    Sharpley AL, Vassallo CM, Pooley EC, et al. Allelic variation in the 5-HT2C receptor (HT2RC) and the increase in slow wave sleep produced by olanzapine. Psychopharmacology (Berl) 2001 Jan 1; 153(2): 271–2CrossRefGoogle Scholar
  120. 120.
    Lindberg N, Virkkunen M, Tani P, et al. Effect of a single-dose of olanzapine on sleep of healthy females and males. Int Clin Psychopharmacol 2002 Jul; 17(4): 177–84PubMedCrossRefGoogle Scholar
  121. 121.
    Gimenez S, Clos S, Romero S, et al. Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers. Psychopharmacoloy (Berl) 2007 Mar; 190(4): 507–16CrossRefGoogle Scholar
  122. 122.
    Cohrs S, Rodenbeck A, Guan Z, et al. Sleep-promoting properties of quetiapine in healthy subjects. Psychopharmacology (Berl) 2004 Jul; 174(3): 421–9Google Scholar
  123. 123.
    Cohrs S, Meier A, Neumann AC, et al. Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects. J Clin Psychiatry 2005 Aug; 66(8): 989–96PubMedCrossRefGoogle Scholar
  124. 124.
    Patat A, Rosenzweig P, Miget N, et al. Effects of 50 mg amisulpride on EEG, psychomotor and cognitive functions in healthy sleep deprived subjects. Fundam Clin Pharmacol 1999; 13(5): 582–94PubMedCrossRefGoogle Scholar
  125. 125.
    Kiser RS, Cohen HM, Freedenfeld RN, et al. Olanzapine for the treatment of fibromyalgia symptoms. J Pain Symptom Manage. 2001 Aug; 22(2): 704–8PubMedCrossRefGoogle Scholar
  126. 126.
    Shemo M, Shemo JPD, Anderson M. Beneficial effects of quetiapine treatment in patients with fibromyalgia [abstract]. J Neuropsychiatry Clin Neurosci Spring 2003; 15(2): 282Google Scholar
  127. 127.
    Rico-Villademoros F, Hidalgo J, Dominguez I, et al. Atypical antipsychotics in the treatment of fibromyalgia: a case series with olanzapine. Prog Neuropsychopharmacol Biol Psychiatry 2005 Jan; 29(1): 161–4PubMedCrossRefGoogle Scholar
  128. 128.
    Freedenfeld RN, Murray M, Fuchs PN, et al. Decreased pain and improved quality of life in fibromyalgia patients treated with olanzapine, an atypical neuroleptic. Pain Pract 2006 Jun; 6(2): 112–8PubMedCrossRefGoogle Scholar
  129. 129.
    Hidalgo J, Rico-Villademoros F, Calandre EP. An open-label study of quetiapine in the treatment of fibromyalgia. Prog Neuropsychopharmacol Biol Psychiatry 2007 Jan; 31(1): 71–7PubMedCrossRefGoogle Scholar
  130. 130.
    Calandre EP, Hidalgo J, Rico-Villademoros F. Use of ziprasidone in patients with fibromyalgia: a case series. Rheumatol Int 2007 Mar; 27(5): 473–6PubMedCrossRefGoogle Scholar
  131. 131.
    Rico-Villademoros F, Hidalgo J, Morillas-Arques P, et al. An open-label study of levopromazine (metho-trimeprazine) as an add-on therapy in fibromyalgia management. Clin Exp Rheumatol 2009 Sep–Oct; 27 (5 Suppl. 56): S16–20PubMedGoogle Scholar
  132. 132.
    McIntyre A. A study of quetiapine fumarate sustained release in major depression with comorbid fibromyalgia syndrome [ identifier NCT00675896]. US National Institutes of Health, [online]. Available from URL: [Accessed 2011 July 20]
  133. 133.
    Moore NC. Quetiapine compared with placebo in the management of fibromyalgia [ identifier NCT00710918]. US National Institutes of Health, [online]. Available from URL: [Accessed 2011 July 20]
  134. 134.
    Calandre EP. Comparative efficacy and tolerability of quetiapine XR and amitriptyline in the treatment of fibromyalgia [ identifier NCT00766350]. US National Institutes of Health, [online]. Available from URL: [Accessed 2011 July 20]
  135. 135.
    Marchand S. Quetiapine (Seroquel XR) for the treatment of fibromyalgia: a clinical and mechanistic pilot study [ identifier NCT00983320]. US National Institutes of Health, [online]. Available from URL: [Accessed 2011 July 20]
  136. 136.
    Pardini M, Guida S, Primavera A, et al. Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study. Eur Neuropsychopharmacol 2011 Mar; 21(3): 282–6Google Scholar
  137. 137.
    Moore N, Macmillan P, Birur B, et al. Fibromyalgia: efficacy of quetiapine compared with placebo [abstract no. NR08-48: 333]. 164th Annual Meeting of the American Psychiatric Association; 2011 May 14–18; Honolulu (HI)Google Scholar
  138. 138.
    Rico-Villademoros F, Rodréguez López CM, Vélchez Pérez JS, et al. Comparison between quetiapine-XR and amitriptyline in fibromyalgia patients: a 16-week, randomized, open-label, non-inferiority trial [abstract]. Eur J Pain 2011 Sep;5(1): 133Google Scholar
  139. 139.
    Gao K, Ganocy SJ, Gajwani P, et al. A review of sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia: focus on somnolence. J Clin Psychiatry 2008 Feb; 69(2): 302–9PubMedCrossRefGoogle Scholar
  140. 140.
    Wang Z, Kemp DE, Chan PK, et al. Comparisons of the tolerability and sensitivity of quetiapine-XR in the acute treatment of schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and generalized anxiety disorder. Int J Neuropsychopharmacol 2011 Feb; 14(1): 131–42PubMedCrossRefGoogle Scholar
  141. 141.
    Calandre EP, Morillas-Arques P, Rodriguez-Lopez CM, et al. Pregabalin augmentation of quetiapine therapy in the treatment of fibromyalgia. Pharmacopsychiatry 2007 Mar; 40(2): 68–71PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  • Elena P. Calandre
    • 1
  • Fernando Rico-Villademoros
    • 1
  1. 1.Instituto de Neurociencias y Centro de Investigaciones BiomédicasUniversity of GranadaGranadaSpain

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