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Fibromyalgia Symptoms Relieved by Flupirtine: An Open-Label Case Series
Letters to the Editor (0.33%) possessed “progressive eyesight deterioration.” This incidence of suicide in the sight impaired is remarkably similar to a recent World Health Organization estimate of the prevalence of blindness (visual acuity⬍0.05 with best possible correction) in established market economies, which includes Australia:2 0.3% (v2⳱0.03, df⳱1, NS). As the pathologies leading to blindness (e.g., diabetic retinopathy, macular degeneration, glaucoma) almost invariably produce slow deterioration in eyesight, it follows that people with progressive sight loss are not overrepresented in De Leo et al.’s suicide database. Furthermore, people with “progressive eyesight deterioration” would also include those with low vision (acuity⬍0.3). Given that the prevalence of low vision among Australians is 1.04%,3 it could be argued that people with eyesight deterioration are actually underrepresented in the suicide population. De Leo et al. provide a cursory summary of 19 suicide cases of people with either hearing or visual “sensory deprivation” or in one case, both. They claim that the gender ratio (male:female) in their sample differed from the overall suicide gender ratio of 4:1. This claim is also not justified given their small sample size: for eyesight-impaired cases (9:3, v2⳱0.19, NS), for the hearing impaired cases (7:0, v2⳱1.75, NS), or overall (16:3, v2⳱0.17, NS). Furthermore, in many of their suicide cases there are documented preexisting psychopathologies and/or recent major life stressors, which, independent of the sensory loss, may have predisposed the person to suicidal ideation and behavior. There is little doubt that losing one’s sight is a traumatic event that can precipitate a depressive reaction.4 Major adjustments have to be made in the patient’s life, which require a strong preexisting Psychosomatics 41:4, July-August 2000
psychological and social support base. For those who have neither, adjustment disorders can arise and in turn, this may lead to suicidal ideation, but other earlier studies indicate that actual attempts at suicide among those that are blind are “very rare.”4 We see no compelling reasons for De Leo’s conclusion that psychopathology, which can be linked solely to sight loss or fear of sight loss, is more likely to lead to suicide than psychopathology caused by any other physical or psychological trauma (e.g., paraplegia). In the current climate of limited health funding for rehabilitation and support for those with low vision, we believe the authors’ recommendations to ophthalmologists are unjustified. Trevor J. Hine, Ph.D. School of Applied Psychology, Griffith University, Mt. Gravatt, Queensland, Australia Nikki J. Pitchford, Ph.D. Fred A.A. Kingdom, Ph.D. Robert Koenekoop, M.D., Ph.D. Department of Ophthalmology, McGill University, Montre´al, Que´bec, Canada References
1. De Leo D, Hickey PA, Meneghel G, et al: Blindness, fear of sight loss, and suicide. Psychosomatics 1999; 40:339–344 2. Thylefors B, Ne´grel AD, Pararajasegaram R, et al: Global data on blindness. Bull World Health Organ 1995; 73:115–121 3. Australian Bureau of Statistics: National Health Survey–Summary of Results 1995; Catalogue No: 4364.0 4. Fitzgerald RG: Reactions to blindness: an exploratory study of adults with recent loss of sight. Arch Gen Psychiatry 1970; 22:370– 379
In Reply Hine et al. expressed concerns regarding our paper. Our paper was correctly published in the case reports section. Case reports probe details of individual cases to explore and enhance
understanding of clinical issues and develop hypotheses for future testing. It was also not our intention to provide an assessment of the relative risk for suicide associated with fear of losing eyesight. As stated several times in the manuscript, the small number of cases involving fear of losing sight did not permit epidemiological evaluations. Again our remarks concerning the gender distribution, instead of having an epidemiological dimension, was simply to attract attention to the possibility that men may have greater difficulty adjusting to visual impairment than women. The data that we analyzed are based on psychological autopsies. What prompted our report was noticing that only 2 of 7 hearing-impaired suicides were substantially driven by distress about their sensory impairment, 11 of 12 visually impaired suicides were driven by this distress. Hine et al. assert that in the current climate of limited health funding they found our recommendations that ophthalmologists and sight rehabilitation workers be attentive to these issues and develop collaborations with mental health professionals unjustified. We suggest that it is better to respond to the sound of a fire alarm than to wait for confirmation of fire. The needs of distressed visually impaired persons will not be met by looking the other way. Diego De Leo, M.D., Ph.D. Portia Hickey, Gaia Meneghel, M.D. Christopher H. Cantor, M.B., B.S., MRCPsych, FRANZP Australian Institute for Suicide Prevention, Griffith University, Queensland, Australia
Fibromyalgia Symptoms Relieved by Flupirtine: An Open-Label Case Series TO THE EDITOR: Fibromyalgia is a chronic, idiopathic, and still controver371
Letters to the Editor sial syndrome characterized by moderate to severe musculoskeletal pain, a specific sleep disturbance, chronic fatigue, and often major depression.1 Currently there are no specific treatments for fibromyalgia.1 This report describes the successful use of the nonopiate analgesic drug flupirtine to treat the pain and other associated symptoms in a consecutive series of four patients with fibromyalgia. Case Reports Case 1. Ms. S. is a 39-year-old married woman with approximately 3 years of fibromyalgia symptoms, characterized by pain in multiple joints, chronic fatigue, insomnia, and recent major depression. After numerous trials of nonsteroidal anti-inflammatory drugs, steroids, multiple antidepressant trials, opiates, and other strategies failed to relieve chronic headache and fibromyalgia symptoms, flupirtine was imported from Germany in an effort to reduce her pain. The flupirtine (up to 600 mg/day) did nothing to alter her headache pain but completely abolished her fibromyalgia pain, sleep disturbance, fatigue, and depressive symptoms within several days. Ms. S. has remained free of fibromyalgia symptoms for more than 18 months, receiving flupirtine at a dosage of 100 mg bid. Case 2. Ms. P. is a 29-year-old single woman with several years of fibromyalgia symptoms, including multiple areas of joint pain, chronic fatigue, severe insomnia, and treatment-resistant major depression. Despite multiple trials of antidepressants and analgesics, Ms. P. remained symptomatic. After the experience of Case 1, flupirtine was prescribed (300 mg/day), and within several days, Ms. P. received moderate relief from her joint pain and sleep disturbance. However, she did not achieve full relief from pain and her chronic fa372
tigue. Because of the difficulty and expense in obtaining the drug, Ms. P. discontinued the flupirtine after 3 weeks. Case 3. Ms. J. is a 60-year-old woman with 40 years of bipolar disorder and approximately 15 years of fibromyalgia symptoms, with severe joint pains and fatigue. Treatment with nonsteroidal anti-inflammatory drugs, steroids, multiple mood drugs, and other strategies failed to relieve her pain and fatigue. Flupirtine was prescribed, and at a dosage of 100 mg qhs, it completely abolished her fibromyalgia pain and substantially improved her fatigue. Initial sedation and dizziness resolved after several days. Ms. J. continues to have the first full and sustained remission (more than 1 year) from her fibromyalgia. Case 4. Ms. B. is a 54-year-old woman with at least 5 years of systemic lupus erythrematosus, diffuse myofascial pain consistent with a fibromyalgia diagnosis, and recurrent major depression. Numerous trials of corticosteroids, nonsteroidal anti-inflammatory drugs, opiate analgesics, and antidepressants failed to relieve her fibromyalgia symptoms. Flupirtine (100 mg qhs) was added to her medication regimen and increased over a 2-week period to 300 mg qhs. For the first time since the onset of her fibromyalgia, Ms. B. experienced substantial and gratifying relief from her myofascial pain. During her 5-month flupirtine trial, she also described a “miraculous” increase in energy and ability to concentrate. She has experienced no significant adverse effects. This report describes the successful use of flupirtine (mean dose⳱160 mg/day) to treat fibromyalgia pain and other associated symptoms in four consecutive patients. Cases 1, 3, and 4 had the most dramatic responses to flupirtine. Case 2, who had extensive psychiatric comorbidity, had a clear but
only partial response. Flupirtine is a nonopiate analgesic approved in Europe for general nocioceptive pain.1 Flupirtine acts in the central nervous system through nonopiate pain pathways, possibly involving the thalamus or spinal pain pathways.2–4 Flupirtine is clearly distinct from the opiates in action, and it exhibits no known abuse potential, lacks withdrawal effects, and tolerance to its antinocioceptive effects has not been observed.1 It is important to note that flupirtine relieved not only the pain but also other symptoms associated with fibromyalgia, such as insomnia, depressed mood, cognitive dysfunction, and fatigue. These openlabel results were quite striking, and if confirmed in a controlled trial, flupirtine may represent the first generally effective and specific treatment for fibromyalgia. Andrew L. Stoll, M.D. Belmont, MA References
1. Goldenberg DL: Fibromyalgia syndrome a decade later: what have we learned? Arch Intern Med 1999; 159:777–785 2. Bleyer H, Calsson KH, Erkel HJ, et al: Flupirtine depresses nocioceptive activity evoked in rat thalamus. Eur J Pharmacol 1988; 151:259–265 3. Nickel B, Borbe Ho, Szelenyi I: Investigations with the novel non-opioid analgesic flupirtine in regard to possible benzodiazepine-like abuse inducing potential. Arzneimittelforschung 1990; 40:905–908 4. Nickel B, Jakovlev V, Szelenyi I: The effect of flupirtine, various analgesics and muscle relaxants on skeletal muscle tone in the conscious rat. Arzneimittelforschung 1990; 40:909–911
Psychological Factors, Immunity, and Heart Disease TO THE EDITOR: Studies of psychiatric patients, community samples, and patients with known heart disease demonstrated that depressive disorders, stressful life events, and poor social Psychosomatics 41:4, July-August 2000
psychological and social support base. For those who have neither, adjustment disorders can arise and in turn, this may lead to suicidal ideation, but other earlier studies indicate that actual attempts at suicide among those that are blind are “very rare.”4 We see no compelling reasons for De Leo’s conclusion that psychopathology, which can be linked solely to sight loss or fear of sight loss, is more likely to lead to suicide than psychopathology caused by any other physical or psychological trauma (e.g., paraplegia). In the current climate of limited health funding for rehabilitation and support for those with low vision, we believe the authors’ recommendations to ophthalmologists are unjustified. Trevor J. Hine, Ph.D. School of Applied Psychology, Griffith University, Mt. Gravatt, Queensland, Australia Nikki J. Pitchford, Ph.D. Fred A.A. Kingdom, Ph.D. Robert Koenekoop, M.D., Ph.D. Department of Ophthalmology, McGill University, Montre´al, Que´bec, Canada References
1. De Leo D, Hickey PA, Meneghel G, et al: Blindness, fear of sight loss, and suicide. Psychosomatics 1999; 40:339–344 2. Thylefors B, Ne´grel AD, Pararajasegaram R, et al: Global data on blindness. Bull World Health Organ 1995; 73:115–121 3. Australian Bureau of Statistics: National Health Survey–Summary of Results 1995; Catalogue No: 4364.0 4. Fitzgerald RG: Reactions to blindness: an exploratory study of adults with recent loss of sight. Arch Gen Psychiatry 1970; 22:370– 379
In Reply Hine et al. expressed concerns regarding our paper. Our paper was correctly published in the case reports section. Case reports probe details of individual cases to explore and enhance
understanding of clinical issues and develop hypotheses for future testing. It was also not our intention to provide an assessment of the relative risk for suicide associated with fear of losing eyesight. As stated several times in the manuscript, the small number of cases involving fear of losing sight did not permit epidemiological evaluations. Again our remarks concerning the gender distribution, instead of having an epidemiological dimension, was simply to attract attention to the possibility that men may have greater difficulty adjusting to visual impairment than women. The data that we analyzed are based on psychological autopsies. What prompted our report was noticing that only 2 of 7 hearing-impaired suicides were substantially driven by distress about their sensory impairment, 11 of 12 visually impaired suicides were driven by this distress. Hine et al. assert that in the current climate of limited health funding they found our recommendations that ophthalmologists and sight rehabilitation workers be attentive to these issues and develop collaborations with mental health professionals unjustified. We suggest that it is better to respond to the sound of a fire alarm than to wait for confirmation of fire. The needs of distressed visually impaired persons will not be met by looking the other way. Diego De Leo, M.D., Ph.D. Portia Hickey, Gaia Meneghel, M.D. Christopher H. Cantor, M.B., B.S., MRCPsych, FRANZP Australian Institute for Suicide Prevention, Griffith University, Queensland, Australia
Fibromyalgia Symptoms Relieved by Flupirtine: An Open-Label Case Series TO THE EDITOR: Fibromyalgia is a chronic, idiopathic, and still controver371
Letters to the Editor sial syndrome characterized by moderate to severe musculoskeletal pain, a specific sleep disturbance, chronic fatigue, and often major depression.1 Currently there are no specific treatments for fibromyalgia.1 This report describes the successful use of the nonopiate analgesic drug flupirtine to treat the pain and other associated symptoms in a consecutive series of four patients with fibromyalgia. Case Reports Case 1. Ms. S. is a 39-year-old married woman with approximately 3 years of fibromyalgia symptoms, characterized by pain in multiple joints, chronic fatigue, insomnia, and recent major depression. After numerous trials of nonsteroidal anti-inflammatory drugs, steroids, multiple antidepressant trials, opiates, and other strategies failed to relieve chronic headache and fibromyalgia symptoms, flupirtine was imported from Germany in an effort to reduce her pain. The flupirtine (up to 600 mg/day) did nothing to alter her headache pain but completely abolished her fibromyalgia pain, sleep disturbance, fatigue, and depressive symptoms within several days. Ms. S. has remained free of fibromyalgia symptoms for more than 18 months, receiving flupirtine at a dosage of 100 mg bid. Case 2. Ms. P. is a 29-year-old single woman with several years of fibromyalgia symptoms, including multiple areas of joint pain, chronic fatigue, severe insomnia, and treatment-resistant major depression. Despite multiple trials of antidepressants and analgesics, Ms. P. remained symptomatic. After the experience of Case 1, flupirtine was prescribed (300 mg/day), and within several days, Ms. P. received moderate relief from her joint pain and sleep disturbance. However, she did not achieve full relief from pain and her chronic fa372
tigue. Because of the difficulty and expense in obtaining the drug, Ms. P. discontinued the flupirtine after 3 weeks. Case 3. Ms. J. is a 60-year-old woman with 40 years of bipolar disorder and approximately 15 years of fibromyalgia symptoms, with severe joint pains and fatigue. Treatment with nonsteroidal anti-inflammatory drugs, steroids, multiple mood drugs, and other strategies failed to relieve her pain and fatigue. Flupirtine was prescribed, and at a dosage of 100 mg qhs, it completely abolished her fibromyalgia pain and substantially improved her fatigue. Initial sedation and dizziness resolved after several days. Ms. J. continues to have the first full and sustained remission (more than 1 year) from her fibromyalgia. Case 4. Ms. B. is a 54-year-old woman with at least 5 years of systemic lupus erythrematosus, diffuse myofascial pain consistent with a fibromyalgia diagnosis, and recurrent major depression. Numerous trials of corticosteroids, nonsteroidal anti-inflammatory drugs, opiate analgesics, and antidepressants failed to relieve her fibromyalgia symptoms. Flupirtine (100 mg qhs) was added to her medication regimen and increased over a 2-week period to 300 mg qhs. For the first time since the onset of her fibromyalgia, Ms. B. experienced substantial and gratifying relief from her myofascial pain. During her 5-month flupirtine trial, she also described a “miraculous” increase in energy and ability to concentrate. She has experienced no significant adverse effects. This report describes the successful use of flupirtine (mean dose⳱160 mg/day) to treat fibromyalgia pain and other associated symptoms in four consecutive patients. Cases 1, 3, and 4 had the most dramatic responses to flupirtine. Case 2, who had extensive psychiatric comorbidity, had a clear but
only partial response. Flupirtine is a nonopiate analgesic approved in Europe for general nocioceptive pain.1 Flupirtine acts in the central nervous system through nonopiate pain pathways, possibly involving the thalamus or spinal pain pathways.2–4 Flupirtine is clearly distinct from the opiates in action, and it exhibits no known abuse potential, lacks withdrawal effects, and tolerance to its antinocioceptive effects has not been observed.1 It is important to note that flupirtine relieved not only the pain but also other symptoms associated with fibromyalgia, such as insomnia, depressed mood, cognitive dysfunction, and fatigue. These openlabel results were quite striking, and if confirmed in a controlled trial, flupirtine may represent the first generally effective and specific treatment for fibromyalgia. Andrew L. Stoll, M.D. Belmont, MA References
1. Goldenberg DL: Fibromyalgia syndrome a decade later: what have we learned? Arch Intern Med 1999; 159:777–785 2. Bleyer H, Calsson KH, Erkel HJ, et al: Flupirtine depresses nocioceptive activity evoked in rat thalamus. Eur J Pharmacol 1988; 151:259–265 3. Nickel B, Borbe Ho, Szelenyi I: Investigations with the novel non-opioid analgesic flupirtine in regard to possible benzodiazepine-like abuse inducing potential. Arzneimittelforschung 1990; 40:905–908 4. Nickel B, Jakovlev V, Szelenyi I: The effect of flupirtine, various analgesics and muscle relaxants on skeletal muscle tone in the conscious rat. Arzneimittelforschung 1990; 40:909–911
Psychological Factors, Immunity, and Heart Disease TO THE EDITOR: Studies of psychiatric patients, community samples, and patients with known heart disease demonstrated that depressive disorders, stressful life events, and poor social Psychosomatics 41:4, July-August 2000