- Email: [email protected]
Is rTMS a therapeutic option in chronic pain syndrome? Insights from the treatment of fibromyalgia
Ò
PAIN 152 (2011) 1447–1448
www.elsevier.com/locate/pain
Commentary
Is rTMS a therapeutic option in chronic pain syndrome? Insights from the treatment of fibromyalgia Repetitive transcranial magnetic stimulation (rTMS) of the cerebral cortex has been tested as a treatment tool for various neurological and psychiatric diseases. However, the effects of rTMS, although significant, are generally weak and of short duration. In clinical practice, rTMS is approved for therapeutic use only in depression in several countries, including the United States [21]. To be specific, rTMS has received U.S. Food and Drug Administration (FDA) approval for ‘‘the treatment of major depressive disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication’’ [15]. A particular combination of parameters is specified (intensity: 120% of motor threshold; frequency: 10 Hz; target: left dorsolateral prefrontal cortex) [19] and the treatment requires daily rTMS sessions for 3 weeks or more. The antidepressant effects are clinically meaningful, but of variable magnitude and duration between patients. In addition, only few studies have addressed the problem of the maintenance therapy in patients whose condition has responded to the initial rTMS course [14,17]. In other clinical conditions, rTMS did not reach the same level of evidence for therapeutic application, largely because the effects were considered to be too brief to have a real impact on the management of what is a very chronic disease. In the late 1990’s, analgesic effects of rTMS applied at high frequency (10 Hz) over the precentral motor cortex were first reported in patients with drug-resistant chronic neuropathic pain [10,12]. Since that time, rTMS effects have been reported in a variety of pain conditions [8,9], but a routine therapeutic application was not the primary objective of these studies. Rather the initial reports were mostly the results of single sessions, sometimes repeated for a week [7]. In this issue of Pain, Mhalla et al. provide the first evidence for long-term effectiveness of an initial rTMS course followed by maintenance therapy in fibromyalgia patients [16]. The treatment protocol consisted of a 1-week initial course followed by maintenance sessions for up to 5 months after the induction phase. By means of this protocol, analgesic effects were maintained for up to 6 months. Pain relief was associated with an improvement in fatigue and other items related to quality of life. These results are important and introduce the possibility that a protocol of noninvasive cortical stimulation extended over a long period of time could be a therapeutic alternative to the pharmacological or nonpharmacological treatment of diverse chronic pain syndromes. For example, the application of such a protocol could be considered for treating drug-resistant chronic neuropathic pain, a condition that has been treated by invasive cortical stimulation with surgically implanted epidural electrodes [3]. On the other hand, because invasive cortical stimulation has a mechanism of action probably very close to that of rTMS [13] and ensures a more
lasting effectiveness [11], one might ask whether this would be greater value of invasive epidural stimulation compared to noninvasive stimulation as a treatment option in fibromyalgia. Until the recent emergence of new drugs that showed significant efficacy in fibromyalgia, its pharmacological treatment was generally disappointing [18]. Pregabalin was the first medication approved by the FDA for fibromyalgia, followed soon by two serotonin-norepinephrine reuptake inhibitors, duloxetine and milnacipran. Besides drugs, nonpharmacological therapies have gained importance in the treatment of fibromyalgia and include exercise [5] and cognitive behavioral therapy [2]. In the author’s opinion, rTMS should be a second-line or add-on therapy, as in the case for depression, potentially capable of enhancing the response to the drugs [20]. However, one exciting perspective in the treatment of fibromyalgia could be the combination of rTMS with exercise or cognitive training. This proposal follows from the encouraging results recently obtained with combined strategies for treatment the motor dysfunction of hemiparetic stroke patients [6] or the cognitive dysfunctions of patients with Alzheimer’s disease [1]. Before considering therapeutic application of rTMS in fibromyalgia, however, the present results obtained by Mhalla et al. need to be confirmed by other teams, preferably in the context of a multicenter randomized controlled trial. The question is whether it is better to replicate this study with its ‘‘classical’’ stimulation setting (high-frequency rTMS, precentral target) or to perform new studies with a combination of rTMS and exercise or cognitive training, and/ or to test other parameters or techniques of transcranial stimulation, such as transcranial direct current stimulation (tDCS). In fact, tDCS was shown to produce positive effects on fibromyalgia [4,22], and compared to high-frequency rTMS, tDCS offers the advantage of being delivered by a portable device. The challenge is considerable: fibromyalgia is a chronic widespread pain condition that is estimated to affect more than 1% of the general population, up to 5 million adults in the United States alone. In addition, future studies in fibromyalgia patients should have as their objective the ability to improve the different dimensions (pain, sleep, fatigue, and cognitive disturbances) with which this multifaceted disease presents. Conflict of interest statement I declare no conflict of interest related to this commentary. References [1] Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG, Rabey JM. Beneficial effect of repetitive transcranial magnetic
0304-3959/$36.00 Ó 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2011.03.004
1448
[2]
[3]
[4]
[5]
[6]
[7]
[8] [9]
[10]
[11]
[12] [13]
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Commentary / PAIN 152 (2011) 1447–1448
stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study. J Neural Transm, in press. Bernardy K, Füber N, Köllner V, Häuser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome—a systematic review and metaanalysis of randomized controlled trials. J Rheumatol 2010;37:1991–2005. Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, Simpson BA, Taylor RS. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14:952–70. Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum 2006;54:3988–98. Häuser W, Klose P, Langhorst J, Moradi B, Steinbach M, Schiltenwolf M, Busch A. 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:R79. Kakuda W, Abo M, Kobayashi K, Momosaki R, Yokoi A, Fukuda A, Ishikawa A, Ito H, Tominaga A. Low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for poststroke patients with upper limb hemiparesis: preliminary study of a 15-day protocol. Int J Rehabil Res, in press. Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry 2005;76:833–8. Lefaucheur JP. The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol Clin 2006;36:117–24. Lefaucheur JP, Antal A, Ahdab R, Ciampi de Andrade D, Fregni F, Khedr EM, Nitsche M, Paulus W. The use of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to relieve pain. Brain Stimul 2008;1:337–44. Lefaucheur JP, Drouot X, Keravel Y, Nguyen JP. Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. Neuroreport 2001;12:2963–5. Lefaucheur JP, Drouot X, Ménard-Lefaucheur I, Nguyen JP. Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol Clin 2004;34:91–5. Lefaucheur JP, Drouot X, Pollin B, Keravel Y, Nguyen JP. Chronic pain treated by rTMS of motor cortex. Electroencephalogr Clin Neurophysiol 1998;107:92. Lefaucheur JP, Holsheimer J, Goujon C, Keravel Y, Nguyen JP. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain. Exp Neurol 2010;223:609–14.
[14] Li X, Nahas Z, Anderson B, Kozel FA, George MS. Can left prefrontal rTMS be used as a maintenance treatment for bipolar depression? Depress Anxiety 2004;20:98–100. [15] Melkerson MN, Food and Drug Administration, Public Health Service, Department of Health and Human Services. Special Premarket 510(k) Notification for NeuroStar TMS Therapy System for Major Depressive Disorder, 2008-12-16 (www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf). [16] Mhalla A, Baudic S, Ciampi De Andrade D, Gautron M, Perrot S, Teixeira MJ, Attal N, Bouhassira D. Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. Pain 2011;152:1478–85. [17] O’Reardon JP, Blumner KH, Peshek AD, Pradilla RR, Pimiento PC. Long-term maintenance therapy for major depressive disorder with rTMS. J Clin Psychiatry 2005;66:1524–8. [18] Recla JM. New and emerging therapeutic agents for the treatment of fibromyalgia: an update. J Pain Res 2010;3:89–103. [19] Rosa MA, Rosa MO, Lisanby SH. The Black Book of Repetitive Transcranial Magnetic Stimulation. Parameters of Stimulation in rTMS. Psychiatry Weekly 2011;6: 2011-01-17. [20] Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C, Myczkowski ML, Moreno RA, Marcolin MA. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biol Psychiatry 2005;57:162–6. [21] Schönfeldt-Lecuona C, Cárdenas-Morales L, Freudenmann RW, Kammer T, Herwig U. Transcranial magnetic stimulation in depression—lessons from the multicentre trials. Restor Neurol Neurosci 2010;28:569–76. [22] Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, Boggio PS, Fregni F. Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag 2009;2:53–361.
Jean-Pascal Lefaucheur Faculté de Médecine, Université Paris Est Créteil, Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique, Hôpitaux de Paris, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Créteil, France Tel.: +33 1 4981 2694 E-mail address: [email protected]
PAIN 152 (2011) 1447–1448
www.elsevier.com/locate/pain
Commentary
Is rTMS a therapeutic option in chronic pain syndrome? Insights from the treatment of fibromyalgia Repetitive transcranial magnetic stimulation (rTMS) of the cerebral cortex has been tested as a treatment tool for various neurological and psychiatric diseases. However, the effects of rTMS, although significant, are generally weak and of short duration. In clinical practice, rTMS is approved for therapeutic use only in depression in several countries, including the United States [21]. To be specific, rTMS has received U.S. Food and Drug Administration (FDA) approval for ‘‘the treatment of major depressive disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication’’ [15]. A particular combination of parameters is specified (intensity: 120% of motor threshold; frequency: 10 Hz; target: left dorsolateral prefrontal cortex) [19] and the treatment requires daily rTMS sessions for 3 weeks or more. The antidepressant effects are clinically meaningful, but of variable magnitude and duration between patients. In addition, only few studies have addressed the problem of the maintenance therapy in patients whose condition has responded to the initial rTMS course [14,17]. In other clinical conditions, rTMS did not reach the same level of evidence for therapeutic application, largely because the effects were considered to be too brief to have a real impact on the management of what is a very chronic disease. In the late 1990’s, analgesic effects of rTMS applied at high frequency (10 Hz) over the precentral motor cortex were first reported in patients with drug-resistant chronic neuropathic pain [10,12]. Since that time, rTMS effects have been reported in a variety of pain conditions [8,9], but a routine therapeutic application was not the primary objective of these studies. Rather the initial reports were mostly the results of single sessions, sometimes repeated for a week [7]. In this issue of Pain, Mhalla et al. provide the first evidence for long-term effectiveness of an initial rTMS course followed by maintenance therapy in fibromyalgia patients [16]. The treatment protocol consisted of a 1-week initial course followed by maintenance sessions for up to 5 months after the induction phase. By means of this protocol, analgesic effects were maintained for up to 6 months. Pain relief was associated with an improvement in fatigue and other items related to quality of life. These results are important and introduce the possibility that a protocol of noninvasive cortical stimulation extended over a long period of time could be a therapeutic alternative to the pharmacological or nonpharmacological treatment of diverse chronic pain syndromes. For example, the application of such a protocol could be considered for treating drug-resistant chronic neuropathic pain, a condition that has been treated by invasive cortical stimulation with surgically implanted epidural electrodes [3]. On the other hand, because invasive cortical stimulation has a mechanism of action probably very close to that of rTMS [13] and ensures a more
lasting effectiveness [11], one might ask whether this would be greater value of invasive epidural stimulation compared to noninvasive stimulation as a treatment option in fibromyalgia. Until the recent emergence of new drugs that showed significant efficacy in fibromyalgia, its pharmacological treatment was generally disappointing [18]. Pregabalin was the first medication approved by the FDA for fibromyalgia, followed soon by two serotonin-norepinephrine reuptake inhibitors, duloxetine and milnacipran. Besides drugs, nonpharmacological therapies have gained importance in the treatment of fibromyalgia and include exercise [5] and cognitive behavioral therapy [2]. In the author’s opinion, rTMS should be a second-line or add-on therapy, as in the case for depression, potentially capable of enhancing the response to the drugs [20]. However, one exciting perspective in the treatment of fibromyalgia could be the combination of rTMS with exercise or cognitive training. This proposal follows from the encouraging results recently obtained with combined strategies for treatment the motor dysfunction of hemiparetic stroke patients [6] or the cognitive dysfunctions of patients with Alzheimer’s disease [1]. Before considering therapeutic application of rTMS in fibromyalgia, however, the present results obtained by Mhalla et al. need to be confirmed by other teams, preferably in the context of a multicenter randomized controlled trial. The question is whether it is better to replicate this study with its ‘‘classical’’ stimulation setting (high-frequency rTMS, precentral target) or to perform new studies with a combination of rTMS and exercise or cognitive training, and/ or to test other parameters or techniques of transcranial stimulation, such as transcranial direct current stimulation (tDCS). In fact, tDCS was shown to produce positive effects on fibromyalgia [4,22], and compared to high-frequency rTMS, tDCS offers the advantage of being delivered by a portable device. The challenge is considerable: fibromyalgia is a chronic widespread pain condition that is estimated to affect more than 1% of the general population, up to 5 million adults in the United States alone. In addition, future studies in fibromyalgia patients should have as their objective the ability to improve the different dimensions (pain, sleep, fatigue, and cognitive disturbances) with which this multifaceted disease presents. Conflict of interest statement I declare no conflict of interest related to this commentary. References [1] Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG, Rabey JM. Beneficial effect of repetitive transcranial magnetic
0304-3959/$36.00 Ó 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.pain.2011.03.004
1448
[2]
[3]
[4]
[5]
[6]
[7]
[8] [9]
[10]
[11]
[12] [13]
Ò
Commentary / PAIN 152 (2011) 1447–1448
stimulation combined with cognitive training for the treatment of Alzheimer’s disease: a proof of concept study. J Neural Transm, in press. Bernardy K, Füber N, Köllner V, Häuser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome—a systematic review and metaanalysis of randomized controlled trials. J Rheumatol 2010;37:1991–2005. Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, Simpson BA, Taylor RS. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007;14:952–70. Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum 2006;54:3988–98. Häuser W, Klose P, Langhorst J, Moradi B, Steinbach M, Schiltenwolf M, Busch A. 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:R79. Kakuda W, Abo M, Kobayashi K, Momosaki R, Yokoi A, Fukuda A, Ishikawa A, Ito H, Tominaga A. Low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for poststroke patients with upper limb hemiparesis: preliminary study of a 15-day protocol. Int J Rehabil Res, in press. Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry 2005;76:833–8. Lefaucheur JP. The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol Clin 2006;36:117–24. Lefaucheur JP, Antal A, Ahdab R, Ciampi de Andrade D, Fregni F, Khedr EM, Nitsche M, Paulus W. The use of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to relieve pain. Brain Stimul 2008;1:337–44. Lefaucheur JP, Drouot X, Keravel Y, Nguyen JP. Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. Neuroreport 2001;12:2963–5. Lefaucheur JP, Drouot X, Ménard-Lefaucheur I, Nguyen JP. Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol Clin 2004;34:91–5. Lefaucheur JP, Drouot X, Pollin B, Keravel Y, Nguyen JP. Chronic pain treated by rTMS of motor cortex. Electroencephalogr Clin Neurophysiol 1998;107:92. Lefaucheur JP, Holsheimer J, Goujon C, Keravel Y, Nguyen JP. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain. Exp Neurol 2010;223:609–14.
[14] Li X, Nahas Z, Anderson B, Kozel FA, George MS. Can left prefrontal rTMS be used as a maintenance treatment for bipolar depression? Depress Anxiety 2004;20:98–100. [15] Melkerson MN, Food and Drug Administration, Public Health Service, Department of Health and Human Services. Special Premarket 510(k) Notification for NeuroStar TMS Therapy System for Major Depressive Disorder, 2008-12-16 (www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf). [16] Mhalla A, Baudic S, Ciampi De Andrade D, Gautron M, Perrot S, Teixeira MJ, Attal N, Bouhassira D. Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. Pain 2011;152:1478–85. [17] O’Reardon JP, Blumner KH, Peshek AD, Pradilla RR, Pimiento PC. Long-term maintenance therapy for major depressive disorder with rTMS. J Clin Psychiatry 2005;66:1524–8. [18] Recla JM. New and emerging therapeutic agents for the treatment of fibromyalgia: an update. J Pain Res 2010;3:89–103. [19] Rosa MA, Rosa MO, Lisanby SH. The Black Book of Repetitive Transcranial Magnetic Stimulation. Parameters of Stimulation in rTMS. Psychiatry Weekly 2011;6: 2011-01-17. [20] Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C, Myczkowski ML, Moreno RA, Marcolin MA. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biol Psychiatry 2005;57:162–6. [21] Schönfeldt-Lecuona C, Cárdenas-Morales L, Freudenmann RW, Kammer T, Herwig U. Transcranial magnetic stimulation in depression—lessons from the multicentre trials. Restor Neurol Neurosci 2010;28:569–76. [22] Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, Boggio PS, Fregni F. Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag 2009;2:53–361.
Jean-Pascal Lefaucheur Faculté de Médecine, Université Paris Est Créteil, Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique, Hôpitaux de Paris, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Créteil, France Tel.: +33 1 4981 2694 E-mail address: [email protected]