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Electroconvulsive therapy in patients with depression and fibromyalgia
European Journal of Pain 8 (2004) 371–376 www.EuropeanJournalPain.com
Electroconvulsive therapy in patients with depression and fibromyalgia Martti J. Huuhka b
a,*
€ b, Esa V.J. Leinonen , Maija L. Haanp€ aa
a
a Department of Psychogeriatrics, Tampere University Hospital, Pitk€aniemi Fin-33380, Finland Pain Clinic and Department of Neurosurgery, Helsinki University Hospital, P.O. Box 340, 00029 HUS, Finland
Received 13 May 2003; accepted 5 November 2003 Available online 10 December 2003
Abstract The effect of electroconvulsive therapy (ECT) on depression and other symptoms of fibromyalgia was studied in a prospective 3-month trial in 13 patients with fibromyalgia and concomitant depression. All the patients met the DSM-IV diagnostic criteria for Major Depressive Disorder and fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. The Mont gomery and Asberg Depression Rating Scale (MADRS) and the clinical global impression scale (CGI) were used to assess the severity of depression and the clinical change of the patients. The fibromyalgia impact questionnaire (FIQ) was used to evaluate the severity of the fibromyalgia symptoms. The intensity of pain was evaluated using a 6-point scale (0 ¼ no pain, 5 ¼ very severe pain), and tender point palpation. All assessments were performed at baseline and at follow-up visits, which took place one week, one month and three months after ECT. There was a significant improvement in depression after ECT according to MADRS. Using CGI, six patients were much or very much improved, while four patients were minimally improved and three patients had no change. There was significant improvement in four out of ten FIQ item scores, ‘‘feel good’’, ‘‘fatigue’’, ‘‘anxiety’’ and ‘‘depression’’. No significant change was found in the FIQ item scores ‘‘physical function’’, ‘‘pain’’, ‘‘stiffness’’ and ‘‘morning tiredness’’ or number of tender points and self-reported pain. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on the pain or other physical symptoms of these patients. Ó 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. Keywords: Electroconvulsive therapy; Fibromyalgia; Depression; Pain
1. Introduction Fibromyalgia (FM) is characterised by chronic widespread pain, tenderness, muscle stiffness, sleep problems, fatigue and emotional distress. The etiology and pathophysiology of FM remain elusive. FM has been associated with certain infections (Buskila et al., 1997; Goldenberg, 1999; Thomson and Barkhuizen, 2003), neuroendocrine system disturbance (Adler et al., 2002), biochemical and immunological abnormalities (Richards and Cleare, 2000) and autonomic dysfunction (Rai et al., 2000; Cohen et al., 2000). Psychological and psychosocial factors have also been suggested to influ*
Corresponding author. Tel.: +358-324-73631; fax: +358-324-73610. E-mail address: martti.huuhka@pshp.fi (M.J. Huuhka).
ence the occurrence and persistence of this disorder (Walker et al., 1997; Barsky and Borus, 1999). According to the psychophysical studies, patients with FM and control subjects generally detect sensory stimulation at the same levels, but the level at which these stimuli become unpleasant or felt as pain is lower in FM patients (Gibson et al., 1994; Kosek et al., 1996). The recent fMRI study supports the hypothesis that FM is characterised by cortical and subcortical augmentation of pain processing (Gracely et al., 2002). The clinical diagnosis of FM is based on the history and the physical finding on 11 or more out of 18 specified tender-point sites on digital palpation (Wolfe et al., 1990). Some authors have, however, criticised the classification of FM as a discrete disease, because it is not a well-defined medical condition and consists of non-specific symptoms
1090-3801/$30 Ó 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2003.11.001
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(Croft, 2003; Ehrlich, 2003; Hadler, 2003; Van Houdenhove, 2003). The prevalence of FM is reported to be from 0.5% to 5% in general population, and the majority of the patients are female (White et al., 1999; White and Harth, 2001). Depression is the most common psychiatric disorder associated with FM (Hudson et al., 1985; Epstein et al., 1999; Okifuji et al., 2000). In an analysis of more than 6000 consecutive patients of a rheumatic disease outpatient clinic, those with FM were more depressed than other clinic patients (Hawley and Wolfe, 1993). The lifetime prevalence of severe depression is around 70% in FM patients compared to 13% in patients with arthritis (Hudson et al., 1985; Epstein et al., 1999). Electroconvulsive therapy (ECT) is a safe and effective treatment in affective disorders, especially in major depression (Prudic et al., 1996; APA, 2001; OÕConnor et al., 2001). It has been used since 1938 and has been administered to millions of psychiatric patients. It is estimated that approximately 50 000 patients receive ECT treatments in the United States every year (Beyer et al., 1998). In depression ECT is used mainly for those patients who are refractory to psychopharmacological treatment. Especially in elderly patients, ECT therapy may be better tolerated than psychopharmacological treatment (NIH Consensus Development Panel, 1992). Since the 1940s, there have been reports of beneficial effects of ECT on various pain states (Bloomstein et al., 1996; Mandel, 1975) such as phantom limb pain (Pisetsky, 1946; Bornstein, 1949; Gillis, 1969; Rasmussen and Rummans, 2000), reflex sympathetic dystrophy (King and Nuss, 1993), atypical facial pain (Hampf et al., 1992), postherpetic neuralgia (Sameshima et al., 1999) and central post stroke pain (Doi et al., 1999). On the other hand, some patients have received little or no benefit for their pain from ECT (Salmon et al., 1988; McCance et al., 1996). The mechanism of action of ECT is unknown. To our knowledge, there have been no previous reports on the possible effects of ECT on the pain and other symptoms of FM. The aim of the present study was to evaluate the effect of ECT on depressive symptoms and fibromyalgia in patients with concomitant major depressive disorder (MDD) and FM. Improvement of depressive symptoms was primary and FM symptoms was a secondary outcome measure.
2. Patients and methods 2.1. Patients The study was performed at the Department of Psychiatry, Tampere University Hospital. The rheumatologists and psychiatrists of the catchment area of the Tampere University Hospital were informed about the study and were asked to refer FM patients with refractory depression to psychiatric consultation. The main
inclusion criteria were therapy refractory depression (at least two unsuccessful trials with antidepressants of different types) and the coexistence of FM was secondary. Patients with epilepsy, anticonvulsive medication for any reason, substance abuse or any severe medical or neurological disease were excluded. This study was approved by the Ethics Committee of the Tampere University Hospital. Written informed consent was required from all included patients. The study group consisted of 13 patients, four men and nine women, aged 36–61 years (mean 49 years, SD 7.9 years) with major depression and concomitant primary fibromyalgia syndrome. The fibromyalgia diagnosis had been made by a rheumatologist on all patients and was based on the diagnostic criteria for fibromyalgia of the American College of Rheumatology (Wolfe et al., 1990). All the patients currently met the DSM-IV (American Psychiatric Association, 1994) diagnostic criteria for Major Depressive Disorder. The mean duration of fibromyalgia was 6.1 years (SD 5.7, range 1–14 years) and the mean duration of depressive illness was 7.4 years (SD 6.2, range 1–20 years). Three patients were hospitalised for depression and ten were outpatients. Five patients had at least one other somatic disease of clinical importance, e.g., hypertension (3), diabetes (2) and asthma (1). All patients except one had antidepressant medication: mirtazapine (3), venlafaxine (2), reboxetine (2), fluoxetine (1), amitriptyline (1), paroxetine (1), combination of venlafaxine and amitriptyline (1) or combination of venlafaxine and sertraline (1). Four patients had a small dose anxiolytic medication and three patients had hypnotic medication, whereas none of the patients had antipsychotic medication. NSAIDs were regularly used by five patients, and two of them also used tramadol. The medication was kept constant during the follow-up. 2.2. Methods 2.2.1. ECT procedure ECT was administered by Thymatron DGx (Somatics, Lake Bluff, IL, USA) brief pulse device. The stimulus dosage (milliCoulombs) was adjusted with the age method and was about five times age (Swartz and Abrams, 1996). Anaesthesia was induced with methohexital and muscle relaxation with succinylcholine. The initial dosage was 1 mg/kg of methohexital and 0.5 mg/kg of succinylcholine. All the patients were treated with unilateral ECT to minimise the memory impairment. The number of treatments was eight, except seven in one patient and three in another patient. In the latter case, there was an excellent antidepressive response after three sessions, so further treatments were considered unnecessary. 2.2.2. Assessment methods The baseline demographic and clinical data were assessed one week before the first ECT session. The
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patients were then followed up for three months after ECT. The follow-up assessments were carried out one week, one month and three months after the last ECT session. The Montgomery and Asberg depression rating scale (MADRS) (Montgomery and Asberg, 1979) and the Clinical Global Impression Scale (CGI) (Guy, 1976) were used to assess the severity of depression and the clinical change in the patients, respectively. MADRS was the primary outcome measure. The fibromyalgia impact questionnaire (FIQ), a brief 10 item selfadministered instrument designed to evaluate physical functioning ability was used to evaluate the severity of the FM symptoms (Burckhardt et al., 1991). Additionally, the tender-point examination using digital palpation with the force of 4 kg (Wolfe et al., 1990) was performed at the baseline and at the follow-up visits. During the whole study the patients daily recorded their FM pain and medication in the diary. The intensity of the pain was evaluated using a 6-point scale 0–5 (0 ¼ no pain, 5 ¼ very severe pain). The mean values of the pain scores of the previous week were calculated and used in the statistical analyses to represent the pain at the baseline and at the follow-up visits. Additionally, the pain item of the FIQs (which evaluates pain using a 10 cm visual analogue scale) before the treatment and at the follow-up visits were evaluated individually for each patient. 2.2.3. Statistics The statistical analyses were performed using the Statistical Package for Social Sciences (SPSS, for windows 11.01, SPSS, Chicago, IL, USA). Changes in parameters between pre- and post-ECT periods were analysed by using the StudentÕs two-tail T test. The correlations between the FIQ items, tender point counts, self-assessed pain and MADRS were analysed using regression analysis.
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3. Results There was a significant improvement in depression after ECT according to MADRS (Table 1). Using CGI, 6 out of 13 patients were classified as ‘‘much or very much improved’’, four patients were classified as ‘‘minimally improved’’ and three patients were classified as ‘‘no change’’. Depression was no worse in any patient during the study period when compared with the baseline state. The improvement was significant in four out of ten FIQ item scores, ‘‘feel good’’, ‘‘fatigue’’, ‘‘anxiety’’ and ‘‘depression’’ (Table 1). In the FIQ item scores ‘‘physical function’’, ‘‘pain’’, ‘‘stiffness’’ and ‘‘morning tiredness’’, the change was not significant. Moreover, there was no significant change in the number of tender point count, in the daily self-reported pain score (Table 1), or in the consumption of analgesics. The individual scores of the FIQ item ‘‘pain’’ at baseline and follow-up are given in Fig. 1. Of those four items of the FIQ that were significantly improved after ECT, two items, ‘‘feel good’’ and ‘‘anxiety’’, correlated with the improvement of MADRS (p ¼ 0:037 and p ¼ 0:008, respectively). There was no change during the three months followup in those parameters which had improved after ECT: MADRS (p ¼ 0:191), ‘‘feel good’’ (p ¼ 0:850), ‘‘fatigue’’ (p ¼ 0:671), ‘‘anxiety’’ (p ¼ 0:905) and ‘‘depression’’ (p ¼ 0:787). ECT was well tolerated by all patients with no major complaints or discontinuations due to side effects.
4. Discussion In the present study, we evaluated the effect of ECT on depression and FM symptoms in patients with major depressive disorder (MDD) and concomitant FM. We found that there was a significant improvement in
Table 1 Response to ECT treatment
MADRS (0–60) Self-reports pain (0–5) Tender points (0–18) FIQ: Physical function (0–3) Feel good (0–7) Pain (0–10) Fatigue (0–10) Morning tired (0–10) Stiffness (0–10) Anxiety (0–10) Depression (0–10)
Baseline
After ECT
26.17 5.01 3.13 0.49 15.83 2.33
13.17 10.54 (p < 0:001) 3.00 1.24 (NS) 15.08 2.79 (NS)
1.43 0.80 1.09 0.95 8.92 1.06 8.17 2.02 7.71 2.17 7.38 1.61 8.08 2.08 7.67 1.96
Values at baseline and one week after ECT (mean SD). MADRS, Montgomery and Asberg depression rating scale; FIQ, fibromyalgia impact questionnaire.
1.43 0.54 2.27 1.79 8.25 2.01 6.17 2.36 6.46 2.56 6.46 2.56 5.42 3.12 5.42 3.04
(NS) (p ¼ 0:007) (NS) (p ¼ 0:043) (NS) (NS) (p ¼ 0:015) (p ¼ 0:025)
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Pain in FIQ 11 10 9 8 7 6 5 4 3 2 1 0 Before One week
One month
Three months
Visit Fig. 1. Individual FIQ pain scores before ECT, at one week, one month and three months after ECT.
depressive symptoms (according to MADRS and CGI scales) and in those FIQ items which may reflect mood disorder i.e., ‘‘feel good’’, ‘‘fatigue’’, ‘‘anxiety’’ and ‘‘depression’’. On the contrary, there was no change in the FIQ item scores ‘‘physical function’’, ‘‘pain’’, ‘‘stiffness’’ and ‘‘morning tiredness’’, in the tender point count, or the daily self-reported pain score. The improvement in those parameters with a statistically significant change after ECT was maintained for the whole follow-up period of three months. Our finding of no change in tender-point scores but improvement in depression is consistent with studies using antidepressants (Nicassio et al., 2000; Arnold et al., 2002). Physical function of the present patients did not improve in spite of recovery from depression. This, however, is in accordance with the result of Arnold et al. (2002) who used fluoxetine or placebo in the treatment of FM patients. The physical function in FM patients with long-lasting symptoms, may be related more to pain suffered than to changes in mood. In most of the present patients the symptoms of both had lasted for years. Our study sample consisted of patients with concomitant MDD and fibromyalgia. Despite of ongoing antidepressant drug treatment, all the patients currently met the diagnostic criteria of MDD and the adjunct antidepressant therapy was considered to be indicated. The baseline depression scores were significantly reduced during the ECT. Because the antidepressant drug treatment was kept constant prior to and throughout the whole trial, the mood improvement had to be a consequence of ECT. The mechanism of antidepressant action of ECT is also largely unknown, but is suggested to be connected to monoaminergic signal transduction (Kapur and Mann, 1993). Some neuropeptides and adenosine receptor expression have also been assumed to be involved (Nutt and Glue, 1993). However, the effectiveness of ECT in MDD is well known (Prudic et al., 1996;
Sackeim et al., 2000). In fact, no trial has ever found an antidepressant medication regimen to be more effective than ECT (APA, 2001). There have been some reports of positive effects of ECT on pain associated with various disorders (Pisetsky, 1946; Bornstein, 1949; Gillis, 1969; Mandel, 1975; Hampf et al., 1992; King and Nuss, 1993; Bloomstein et al., 1996; Doi et al., 1999; Sameshima et al., 1999; Rasmussen and Rummans, 2000). To our knowledge, this is the first series of patients suffering from FM and treated with ECT. To avoid cognitive adverse effects, we chose unilateral ECT, which actually did not cause any noticeable memory impairment in our patients. According to previous reports, however, bilateral ECT may be more effective in treating pain syndromes (King and Nuss, 1993; Rasmussen and Rummans, 2000). Two recent meta-analyses of trials of antidepressants have shown tricyclic antidepressants to be moderately effective in the treatment of patients with FM (Arnold et al., 2000; OÕMalley et al., 2000). As the doses used in the randomised controlled studies were lower than those used in depression, it remains unclear whether the improvement is independent of depression. In a recent randomised placebo-controlled studies with citalopram and fluoxetine for patients with FM, good responses were reported in depression and pain relief (Anderberg et al., 2000; Arnold et al., 2002). The mode of action of antidepressants in fibromyalgia is unclear, but is assumed at least partly to be due to the changes in serotonergic and noradrenergic systems (Lawson, 2002). Depression is the most common psychiatric disorder associated with FM (Hudson et al., 1985; Epstein et al., 1999; Okifuji et al., 2000). However, not all these patients are depressed and it is suggested that depression develops independently of the cardinal features of FM, but is related to patientsÕ cognitive appraisal of the effect of pain on their lives (Okifuji et al., 2000). Moreover, the improvement of depression does not always follow reduction of pain symptoms or vice versa. The main limitations of this study are the small sample size and the open-labelled study design. In spite of active information from the rheumatologists and psychiatrists we did not succeed in getting more patients within the time period approved by the ethics committee. This may reflect the prejudice against ECT among patients and rheumatologists and even psychiatrists. The other limitation is that all our patients had relatively severe depressive symptoms (baseline MADRS score 26). Therefore they may not represent depressive FM patients in general. Moreover, the lack of a placebo control group was a weakness in our study. This, however, can be regarded as unethical and is difficult to perform in this type of treatment. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on pain or other physical symptoms of these patients.
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References Adler GK, Manfredsdottir VF, Creskoff KW. Neuroendocrine abnormalities in fibromyalgia. Curr Pain Headache Rep 2002;6:289–98. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press; 1994. Anderberg UM, Marteinsdottir I, von Knorring L. Citalopram in patients with fibromyalgia – a randomized, double-blind, placebocontrolled study. Eur J Pain 2000;4:27–35. Arnold LM, Keck Jr PE, Welge JA. Antidepressant treatment of fibromylagia. A meta-analysis and review. Psychosomatics 2000;41:104–13. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE. A randomised, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med 2002;112:191–7. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med 1999;130:910–21. Beyer JL, Weiner RD, Glenn MD. Electroconvulsive therapy. A programmed text. Washington, DC: American Psychiatric Press Inc.; 1998. Bloomstein JR, Rummans TA, Maruta T, Lin S, Pileggi TS. The use of electroconvulsive therapy in pain patients. Psychosomatics 1996;37:374–9. Bornstein B. Sur le phenomene du membre fantome. Encephale 1949;38:32–46. Burckhardt CS, Clark SH, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18:728–73. Buskila D, Shnaider A, Neuman L, Zilberman D, Hilzenrat N, Sikuler E. Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship. Arch Intern Med 1997;157:2497–500. Cohen H, Neuman L, Shore M, Amir M, Cassuto Y, Buskila D. Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability. Semin Arthritis Rheum 2000;29:217–27. Croft P. Symptoms without pathology: should we try a little tenderness? [editorial]. Rheumatology 2003;42:815–7. Doi N, Nakamura M, Isse K, et al. Electroconvulsive therapy for central post-stroke pain. Abstracts, 9th world congress on pain. Seattle: IASP Press; 1999. p. 436. Ehrlich GE. Pain is Real; Fibromyalgia isnÕt [editorial]. J Rheumatol 2003;30:1666–7. Epstein SA, Kay G, Clauw D, et al. Psychiatric disorders in patients with fibromyalgia. Psychosomatics 1999;40:57–63. Gibson SJ, Littlejohn GO, Gorman MM, Helme RD, Granges G. Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain 1994;58:185–93. Gillis L. The management of painful amputation stumps and phantom limbs. Bibl Psychiatr Neurol 1969;139:159–63. Goldenberg DL. Fibromyalgia a decade later: what have we learned. Arch Intern Med 1999;159:777–85. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002;46:1333–43. Guy W. ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education and Welfare publication ADM 76–338. Rockville, MD: National Institute of Mental Health; 1976. p. 217–22. Hadler NM. ‘‘Fibromyalgia’’ and the medication of misery [editorial]. J Rheumatol 2003;30:1668–70. Hampf G, Kuoppasalmi K, Henriksson M, Achte K. Chronic facial pain together with severe depression is responsive to to electro-
375
convulsive therapy. A case report. Acta Odontol Scand 1992;50:129–32. Hawley DJ, Wolfe F. Depression is not more common in rheumatoid arthritis: a 10-year longitudinal study of 6153 patients with rheumatic disease. J Rheumatol 1993;20:2025–31. Hudson JI, Hudson MS, Pliner LF, Goldenberg DL, Pope HG. Fibromyalgia and major affective disorder: a controlled phenomenology and family history study. Am J Psychiat 1985;142:441–6. Kapur S, Mann JJ. Antidepressant action and the neurobiologic effects of ECT: human studies. In: Coffey CE, editor. The clinical science of electroconvulsive therapy. Washington: American Psychiatric Press; 1993. p. 235–50. King JH, Nuss S. Reflex sympathetic dystrophy treated by electroconvulsive therapy: intractable pain, depression and bilateral electrode. Pain 1993;55:393–6. Kosek E, Ekholm J, Hansson P. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain 1996;68:375–83. Lawson K. Tricyclic antidepressants and fibromyalgia: what is the mechanism of action? Expert Opin Investig Drugs 2002;11:1437–45. Mandel MR. Electroconvulsive therapy for chronic pain associated with depression. Am J Psychiat 1975;132:632–6. McCance S, Hawton K, Brighous Ed, Glynn C. Does electroconvulsive therapy (ECT) have any role in the management of intractable thalamic pain? Pain 1996;68:129–31. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiat 1979;134:382–9. Nicassio PM, Weissman MH, Schuman C, Young CW. The role of generalized pain and pain behavior in tender point scores in fibromyalgia. J Rheumatol 2000;27:1056–62. NIH Consensus Development Panel on Depression in Late Life: Diagnosis and treatment of depression in late life. JAMA 1992; 268: 1018–24. Nutt DJ, Glue P. The neurobiology of ECT: animal studies. In: Coffey CE, editor. The clinical science of electroconvulsive therapy. Washington: American Psychiatric Press; 1993. p. 213–34. OÕConnor MK, Knapp R, Husain M, et al. The influence of age on the response of major depression to electroconvulsive therapy. A C.O.R.E. Report. Am J Geriat Psychiat 2001;9:382–90. Okifuji A, Turk DC, Sherman JJ. Evalution of the relationships between depression and fibromyalgia syndrome: why arenÕt all patients depressed? J Rheumatol 2000;27:212–9. OÕMalley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL. Treatment of fibromyalgia with antidepressants: a metaanalysis. J Gen Int Med 2000;15:659–66. Pisetsky J. The disappearance of painful phantom limbs after electric shock treatment. Am J Psychiat 1946;102:599–601. Prudic J, Haskett RF, Mulsant B, et al. Resistance to antidepressant medications and short-term clinical response to ECT. Am J Psychiat 1996;153:985–92. Rai SR, Broulillard D, Simson CS, Hopman WM, Abdollah H. Dysautonomia among patients with fibromyalgia: a noninvasive assessment. J Rheumatol 2000;27:2660–5. Rasmussen KG, Rummans TA. Electroconvulsive therapy for phantom limb pain. Pain 2000;85:297–9. Richards S, Cleare A. Fibromyalgia: biological correlates. Curr Opin Psychiat 2000;13:623–8. Sackeim HA, Prudic J, Devanand DP, et al. A prospective, randomised, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiat 2000;57:425–34. Salmon JB, Hanna MH, Williams M, Toone B, Wheeler M. Thalamic pain – the effect of electroconvulsive therapy. Pain 1988;33:67–71. Sameshima T, Doi N, Mera H, et al. Electroconvulsive therapy reduces pain in postherpetic neuralgia. Abstracts, 9th world congress on pain. Seattle: IASP Press; 1999. p. 191.
376
M.J. Huuhka et al. / European Journal of Pain 8 (2004) 371–376
Swartz CM, Abrams R. ECT instruction manual. 6th ed. Lake Bluff, IL: Somatics Inc.; 1996. The Practice of Electroconvulsive Therapy. Recommendations for treatment, training, and privileging. A Task Force Report of the American Psychiatric Association. Washington DC: American Psychiatric Association (APA); 2001. Thomson ME, Barkhuizen A. Fibromyalgia, hepatitis C infection, and the cytocine connection. Curr Pain Headache Rep 2003;7:342–7. Walker EA, Keegan D, Gardner G, Sullivan M, Katon WJ, Bernstein D. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: l. Psychiatric diagnosis and functional disability. Psychosom Med 1997;59:567–71.
Van Houdenhove B. Fibromyalgia a challenge for modern medicine [editorial]. Clin Rheumatol 2003;22:1–5. White KP, Speechley M, Harth M, Ostbye T. The London fibromyalgia epidemiology study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol 1999;26: 1570–6. White KP, Harth M. Classification, epidemiology and natural history of fibromyalgia. Curr Pain Headache Rep 2001;4:320–9. Wolfe F, Smythe HA, Yunus MG, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–72.
Electroconvulsive therapy in patients with depression and fibromyalgia Martti J. Huuhka b
a,*
€ b, Esa V.J. Leinonen , Maija L. Haanp€ aa
a
a Department of Psychogeriatrics, Tampere University Hospital, Pitk€aniemi Fin-33380, Finland Pain Clinic and Department of Neurosurgery, Helsinki University Hospital, P.O. Box 340, 00029 HUS, Finland
Received 13 May 2003; accepted 5 November 2003 Available online 10 December 2003
Abstract The effect of electroconvulsive therapy (ECT) on depression and other symptoms of fibromyalgia was studied in a prospective 3-month trial in 13 patients with fibromyalgia and concomitant depression. All the patients met the DSM-IV diagnostic criteria for Major Depressive Disorder and fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. The Mont gomery and Asberg Depression Rating Scale (MADRS) and the clinical global impression scale (CGI) were used to assess the severity of depression and the clinical change of the patients. The fibromyalgia impact questionnaire (FIQ) was used to evaluate the severity of the fibromyalgia symptoms. The intensity of pain was evaluated using a 6-point scale (0 ¼ no pain, 5 ¼ very severe pain), and tender point palpation. All assessments were performed at baseline and at follow-up visits, which took place one week, one month and three months after ECT. There was a significant improvement in depression after ECT according to MADRS. Using CGI, six patients were much or very much improved, while four patients were minimally improved and three patients had no change. There was significant improvement in four out of ten FIQ item scores, ‘‘feel good’’, ‘‘fatigue’’, ‘‘anxiety’’ and ‘‘depression’’. No significant change was found in the FIQ item scores ‘‘physical function’’, ‘‘pain’’, ‘‘stiffness’’ and ‘‘morning tiredness’’ or number of tender points and self-reported pain. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on the pain or other physical symptoms of these patients. Ó 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. Keywords: Electroconvulsive therapy; Fibromyalgia; Depression; Pain
1. Introduction Fibromyalgia (FM) is characterised by chronic widespread pain, tenderness, muscle stiffness, sleep problems, fatigue and emotional distress. The etiology and pathophysiology of FM remain elusive. FM has been associated with certain infections (Buskila et al., 1997; Goldenberg, 1999; Thomson and Barkhuizen, 2003), neuroendocrine system disturbance (Adler et al., 2002), biochemical and immunological abnormalities (Richards and Cleare, 2000) and autonomic dysfunction (Rai et al., 2000; Cohen et al., 2000). Psychological and psychosocial factors have also been suggested to influ*
Corresponding author. Tel.: +358-324-73631; fax: +358-324-73610. E-mail address: martti.huuhka@pshp.fi (M.J. Huuhka).
ence the occurrence and persistence of this disorder (Walker et al., 1997; Barsky and Borus, 1999). According to the psychophysical studies, patients with FM and control subjects generally detect sensory stimulation at the same levels, but the level at which these stimuli become unpleasant or felt as pain is lower in FM patients (Gibson et al., 1994; Kosek et al., 1996). The recent fMRI study supports the hypothesis that FM is characterised by cortical and subcortical augmentation of pain processing (Gracely et al., 2002). The clinical diagnosis of FM is based on the history and the physical finding on 11 or more out of 18 specified tender-point sites on digital palpation (Wolfe et al., 1990). Some authors have, however, criticised the classification of FM as a discrete disease, because it is not a well-defined medical condition and consists of non-specific symptoms
1090-3801/$30 Ó 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2003.11.001
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(Croft, 2003; Ehrlich, 2003; Hadler, 2003; Van Houdenhove, 2003). The prevalence of FM is reported to be from 0.5% to 5% in general population, and the majority of the patients are female (White et al., 1999; White and Harth, 2001). Depression is the most common psychiatric disorder associated with FM (Hudson et al., 1985; Epstein et al., 1999; Okifuji et al., 2000). In an analysis of more than 6000 consecutive patients of a rheumatic disease outpatient clinic, those with FM were more depressed than other clinic patients (Hawley and Wolfe, 1993). The lifetime prevalence of severe depression is around 70% in FM patients compared to 13% in patients with arthritis (Hudson et al., 1985; Epstein et al., 1999). Electroconvulsive therapy (ECT) is a safe and effective treatment in affective disorders, especially in major depression (Prudic et al., 1996; APA, 2001; OÕConnor et al., 2001). It has been used since 1938 and has been administered to millions of psychiatric patients. It is estimated that approximately 50 000 patients receive ECT treatments in the United States every year (Beyer et al., 1998). In depression ECT is used mainly for those patients who are refractory to psychopharmacological treatment. Especially in elderly patients, ECT therapy may be better tolerated than psychopharmacological treatment (NIH Consensus Development Panel, 1992). Since the 1940s, there have been reports of beneficial effects of ECT on various pain states (Bloomstein et al., 1996; Mandel, 1975) such as phantom limb pain (Pisetsky, 1946; Bornstein, 1949; Gillis, 1969; Rasmussen and Rummans, 2000), reflex sympathetic dystrophy (King and Nuss, 1993), atypical facial pain (Hampf et al., 1992), postherpetic neuralgia (Sameshima et al., 1999) and central post stroke pain (Doi et al., 1999). On the other hand, some patients have received little or no benefit for their pain from ECT (Salmon et al., 1988; McCance et al., 1996). The mechanism of action of ECT is unknown. To our knowledge, there have been no previous reports on the possible effects of ECT on the pain and other symptoms of FM. The aim of the present study was to evaluate the effect of ECT on depressive symptoms and fibromyalgia in patients with concomitant major depressive disorder (MDD) and FM. Improvement of depressive symptoms was primary and FM symptoms was a secondary outcome measure.
2. Patients and methods 2.1. Patients The study was performed at the Department of Psychiatry, Tampere University Hospital. The rheumatologists and psychiatrists of the catchment area of the Tampere University Hospital were informed about the study and were asked to refer FM patients with refractory depression to psychiatric consultation. The main
inclusion criteria were therapy refractory depression (at least two unsuccessful trials with antidepressants of different types) and the coexistence of FM was secondary. Patients with epilepsy, anticonvulsive medication for any reason, substance abuse or any severe medical or neurological disease were excluded. This study was approved by the Ethics Committee of the Tampere University Hospital. Written informed consent was required from all included patients. The study group consisted of 13 patients, four men and nine women, aged 36–61 years (mean 49 years, SD 7.9 years) with major depression and concomitant primary fibromyalgia syndrome. The fibromyalgia diagnosis had been made by a rheumatologist on all patients and was based on the diagnostic criteria for fibromyalgia of the American College of Rheumatology (Wolfe et al., 1990). All the patients currently met the DSM-IV (American Psychiatric Association, 1994) diagnostic criteria for Major Depressive Disorder. The mean duration of fibromyalgia was 6.1 years (SD 5.7, range 1–14 years) and the mean duration of depressive illness was 7.4 years (SD 6.2, range 1–20 years). Three patients were hospitalised for depression and ten were outpatients. Five patients had at least one other somatic disease of clinical importance, e.g., hypertension (3), diabetes (2) and asthma (1). All patients except one had antidepressant medication: mirtazapine (3), venlafaxine (2), reboxetine (2), fluoxetine (1), amitriptyline (1), paroxetine (1), combination of venlafaxine and amitriptyline (1) or combination of venlafaxine and sertraline (1). Four patients had a small dose anxiolytic medication and three patients had hypnotic medication, whereas none of the patients had antipsychotic medication. NSAIDs were regularly used by five patients, and two of them also used tramadol. The medication was kept constant during the follow-up. 2.2. Methods 2.2.1. ECT procedure ECT was administered by Thymatron DGx (Somatics, Lake Bluff, IL, USA) brief pulse device. The stimulus dosage (milliCoulombs) was adjusted with the age method and was about five times age (Swartz and Abrams, 1996). Anaesthesia was induced with methohexital and muscle relaxation with succinylcholine. The initial dosage was 1 mg/kg of methohexital and 0.5 mg/kg of succinylcholine. All the patients were treated with unilateral ECT to minimise the memory impairment. The number of treatments was eight, except seven in one patient and three in another patient. In the latter case, there was an excellent antidepressive response after three sessions, so further treatments were considered unnecessary. 2.2.2. Assessment methods The baseline demographic and clinical data were assessed one week before the first ECT session. The
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patients were then followed up for three months after ECT. The follow-up assessments were carried out one week, one month and three months after the last ECT session. The Montgomery and Asberg depression rating scale (MADRS) (Montgomery and Asberg, 1979) and the Clinical Global Impression Scale (CGI) (Guy, 1976) were used to assess the severity of depression and the clinical change in the patients, respectively. MADRS was the primary outcome measure. The fibromyalgia impact questionnaire (FIQ), a brief 10 item selfadministered instrument designed to evaluate physical functioning ability was used to evaluate the severity of the FM symptoms (Burckhardt et al., 1991). Additionally, the tender-point examination using digital palpation with the force of 4 kg (Wolfe et al., 1990) was performed at the baseline and at the follow-up visits. During the whole study the patients daily recorded their FM pain and medication in the diary. The intensity of the pain was evaluated using a 6-point scale 0–5 (0 ¼ no pain, 5 ¼ very severe pain). The mean values of the pain scores of the previous week were calculated and used in the statistical analyses to represent the pain at the baseline and at the follow-up visits. Additionally, the pain item of the FIQs (which evaluates pain using a 10 cm visual analogue scale) before the treatment and at the follow-up visits were evaluated individually for each patient. 2.2.3. Statistics The statistical analyses were performed using the Statistical Package for Social Sciences (SPSS, for windows 11.01, SPSS, Chicago, IL, USA). Changes in parameters between pre- and post-ECT periods were analysed by using the StudentÕs two-tail T test. The correlations between the FIQ items, tender point counts, self-assessed pain and MADRS were analysed using regression analysis.
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3. Results There was a significant improvement in depression after ECT according to MADRS (Table 1). Using CGI, 6 out of 13 patients were classified as ‘‘much or very much improved’’, four patients were classified as ‘‘minimally improved’’ and three patients were classified as ‘‘no change’’. Depression was no worse in any patient during the study period when compared with the baseline state. The improvement was significant in four out of ten FIQ item scores, ‘‘feel good’’, ‘‘fatigue’’, ‘‘anxiety’’ and ‘‘depression’’ (Table 1). In the FIQ item scores ‘‘physical function’’, ‘‘pain’’, ‘‘stiffness’’ and ‘‘morning tiredness’’, the change was not significant. Moreover, there was no significant change in the number of tender point count, in the daily self-reported pain score (Table 1), or in the consumption of analgesics. The individual scores of the FIQ item ‘‘pain’’ at baseline and follow-up are given in Fig. 1. Of those four items of the FIQ that were significantly improved after ECT, two items, ‘‘feel good’’ and ‘‘anxiety’’, correlated with the improvement of MADRS (p ¼ 0:037 and p ¼ 0:008, respectively). There was no change during the three months followup in those parameters which had improved after ECT: MADRS (p ¼ 0:191), ‘‘feel good’’ (p ¼ 0:850), ‘‘fatigue’’ (p ¼ 0:671), ‘‘anxiety’’ (p ¼ 0:905) and ‘‘depression’’ (p ¼ 0:787). ECT was well tolerated by all patients with no major complaints or discontinuations due to side effects.
4. Discussion In the present study, we evaluated the effect of ECT on depression and FM symptoms in patients with major depressive disorder (MDD) and concomitant FM. We found that there was a significant improvement in
Table 1 Response to ECT treatment
MADRS (0–60) Self-reports pain (0–5) Tender points (0–18) FIQ: Physical function (0–3) Feel good (0–7) Pain (0–10) Fatigue (0–10) Morning tired (0–10) Stiffness (0–10) Anxiety (0–10) Depression (0–10)
Baseline
After ECT
26.17 5.01 3.13 0.49 15.83 2.33
13.17 10.54 (p < 0:001) 3.00 1.24 (NS) 15.08 2.79 (NS)
1.43 0.80 1.09 0.95 8.92 1.06 8.17 2.02 7.71 2.17 7.38 1.61 8.08 2.08 7.67 1.96
Values at baseline and one week after ECT (mean SD). MADRS, Montgomery and Asberg depression rating scale; FIQ, fibromyalgia impact questionnaire.
1.43 0.54 2.27 1.79 8.25 2.01 6.17 2.36 6.46 2.56 6.46 2.56 5.42 3.12 5.42 3.04
(NS) (p ¼ 0:007) (NS) (p ¼ 0:043) (NS) (NS) (p ¼ 0:015) (p ¼ 0:025)
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Pain in FIQ 11 10 9 8 7 6 5 4 3 2 1 0 Before One week
One month
Three months
Visit Fig. 1. Individual FIQ pain scores before ECT, at one week, one month and three months after ECT.
depressive symptoms (according to MADRS and CGI scales) and in those FIQ items which may reflect mood disorder i.e., ‘‘feel good’’, ‘‘fatigue’’, ‘‘anxiety’’ and ‘‘depression’’. On the contrary, there was no change in the FIQ item scores ‘‘physical function’’, ‘‘pain’’, ‘‘stiffness’’ and ‘‘morning tiredness’’, in the tender point count, or the daily self-reported pain score. The improvement in those parameters with a statistically significant change after ECT was maintained for the whole follow-up period of three months. Our finding of no change in tender-point scores but improvement in depression is consistent with studies using antidepressants (Nicassio et al., 2000; Arnold et al., 2002). Physical function of the present patients did not improve in spite of recovery from depression. This, however, is in accordance with the result of Arnold et al. (2002) who used fluoxetine or placebo in the treatment of FM patients. The physical function in FM patients with long-lasting symptoms, may be related more to pain suffered than to changes in mood. In most of the present patients the symptoms of both had lasted for years. Our study sample consisted of patients with concomitant MDD and fibromyalgia. Despite of ongoing antidepressant drug treatment, all the patients currently met the diagnostic criteria of MDD and the adjunct antidepressant therapy was considered to be indicated. The baseline depression scores were significantly reduced during the ECT. Because the antidepressant drug treatment was kept constant prior to and throughout the whole trial, the mood improvement had to be a consequence of ECT. The mechanism of antidepressant action of ECT is also largely unknown, but is suggested to be connected to monoaminergic signal transduction (Kapur and Mann, 1993). Some neuropeptides and adenosine receptor expression have also been assumed to be involved (Nutt and Glue, 1993). However, the effectiveness of ECT in MDD is well known (Prudic et al., 1996;
Sackeim et al., 2000). In fact, no trial has ever found an antidepressant medication regimen to be more effective than ECT (APA, 2001). There have been some reports of positive effects of ECT on pain associated with various disorders (Pisetsky, 1946; Bornstein, 1949; Gillis, 1969; Mandel, 1975; Hampf et al., 1992; King and Nuss, 1993; Bloomstein et al., 1996; Doi et al., 1999; Sameshima et al., 1999; Rasmussen and Rummans, 2000). To our knowledge, this is the first series of patients suffering from FM and treated with ECT. To avoid cognitive adverse effects, we chose unilateral ECT, which actually did not cause any noticeable memory impairment in our patients. According to previous reports, however, bilateral ECT may be more effective in treating pain syndromes (King and Nuss, 1993; Rasmussen and Rummans, 2000). Two recent meta-analyses of trials of antidepressants have shown tricyclic antidepressants to be moderately effective in the treatment of patients with FM (Arnold et al., 2000; OÕMalley et al., 2000). As the doses used in the randomised controlled studies were lower than those used in depression, it remains unclear whether the improvement is independent of depression. In a recent randomised placebo-controlled studies with citalopram and fluoxetine for patients with FM, good responses were reported in depression and pain relief (Anderberg et al., 2000; Arnold et al., 2002). The mode of action of antidepressants in fibromyalgia is unclear, but is assumed at least partly to be due to the changes in serotonergic and noradrenergic systems (Lawson, 2002). Depression is the most common psychiatric disorder associated with FM (Hudson et al., 1985; Epstein et al., 1999; Okifuji et al., 2000). However, not all these patients are depressed and it is suggested that depression develops independently of the cardinal features of FM, but is related to patientsÕ cognitive appraisal of the effect of pain on their lives (Okifuji et al., 2000). Moreover, the improvement of depression does not always follow reduction of pain symptoms or vice versa. The main limitations of this study are the small sample size and the open-labelled study design. In spite of active information from the rheumatologists and psychiatrists we did not succeed in getting more patients within the time period approved by the ethics committee. This may reflect the prejudice against ECT among patients and rheumatologists and even psychiatrists. The other limitation is that all our patients had relatively severe depressive symptoms (baseline MADRS score 26). Therefore they may not represent depressive FM patients in general. Moreover, the lack of a placebo control group was a weakness in our study. This, however, can be regarded as unethical and is difficult to perform in this type of treatment. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on pain or other physical symptoms of these patients.
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References Adler GK, Manfredsdottir VF, Creskoff KW. Neuroendocrine abnormalities in fibromyalgia. Curr Pain Headache Rep 2002;6:289–98. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press; 1994. Anderberg UM, Marteinsdottir I, von Knorring L. Citalopram in patients with fibromyalgia – a randomized, double-blind, placebocontrolled study. Eur J Pain 2000;4:27–35. Arnold LM, Keck Jr PE, Welge JA. Antidepressant treatment of fibromylagia. A meta-analysis and review. Psychosomatics 2000;41:104–13. Arnold LM, Hess EV, Hudson JI, Welge JA, Berno SE, Keck PE. A randomised, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med 2002;112:191–7. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med 1999;130:910–21. Beyer JL, Weiner RD, Glenn MD. Electroconvulsive therapy. A programmed text. Washington, DC: American Psychiatric Press Inc.; 1998. Bloomstein JR, Rummans TA, Maruta T, Lin S, Pileggi TS. The use of electroconvulsive therapy in pain patients. Psychosomatics 1996;37:374–9. Bornstein B. Sur le phenomene du membre fantome. Encephale 1949;38:32–46. Burckhardt CS, Clark SH, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18:728–73. Buskila D, Shnaider A, Neuman L, Zilberman D, Hilzenrat N, Sikuler E. Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship. Arch Intern Med 1997;157:2497–500. Cohen H, Neuman L, Shore M, Amir M, Cassuto Y, Buskila D. Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability. Semin Arthritis Rheum 2000;29:217–27. Croft P. Symptoms without pathology: should we try a little tenderness? [editorial]. Rheumatology 2003;42:815–7. Doi N, Nakamura M, Isse K, et al. Electroconvulsive therapy for central post-stroke pain. Abstracts, 9th world congress on pain. Seattle: IASP Press; 1999. p. 436. Ehrlich GE. Pain is Real; Fibromyalgia isnÕt [editorial]. J Rheumatol 2003;30:1666–7. Epstein SA, Kay G, Clauw D, et al. Psychiatric disorders in patients with fibromyalgia. Psychosomatics 1999;40:57–63. Gibson SJ, Littlejohn GO, Gorman MM, Helme RD, Granges G. Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain 1994;58:185–93. Gillis L. The management of painful amputation stumps and phantom limbs. Bibl Psychiatr Neurol 1969;139:159–63. Goldenberg DL. Fibromyalgia a decade later: what have we learned. Arch Intern Med 1999;159:777–85. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002;46:1333–43. Guy W. ECDEU Assessment Manual for Psychopharmacology. US Department of Health, Education and Welfare publication ADM 76–338. Rockville, MD: National Institute of Mental Health; 1976. p. 217–22. Hadler NM. ‘‘Fibromyalgia’’ and the medication of misery [editorial]. J Rheumatol 2003;30:1668–70. Hampf G, Kuoppasalmi K, Henriksson M, Achte K. Chronic facial pain together with severe depression is responsive to to electro-
375
convulsive therapy. A case report. Acta Odontol Scand 1992;50:129–32. Hawley DJ, Wolfe F. Depression is not more common in rheumatoid arthritis: a 10-year longitudinal study of 6153 patients with rheumatic disease. J Rheumatol 1993;20:2025–31. Hudson JI, Hudson MS, Pliner LF, Goldenberg DL, Pope HG. Fibromyalgia and major affective disorder: a controlled phenomenology and family history study. Am J Psychiat 1985;142:441–6. Kapur S, Mann JJ. Antidepressant action and the neurobiologic effects of ECT: human studies. In: Coffey CE, editor. The clinical science of electroconvulsive therapy. Washington: American Psychiatric Press; 1993. p. 235–50. King JH, Nuss S. Reflex sympathetic dystrophy treated by electroconvulsive therapy: intractable pain, depression and bilateral electrode. Pain 1993;55:393–6. Kosek E, Ekholm J, Hansson P. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain 1996;68:375–83. Lawson K. Tricyclic antidepressants and fibromyalgia: what is the mechanism of action? Expert Opin Investig Drugs 2002;11:1437–45. Mandel MR. Electroconvulsive therapy for chronic pain associated with depression. Am J Psychiat 1975;132:632–6. McCance S, Hawton K, Brighous Ed, Glynn C. Does electroconvulsive therapy (ECT) have any role in the management of intractable thalamic pain? Pain 1996;68:129–31. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiat 1979;134:382–9. Nicassio PM, Weissman MH, Schuman C, Young CW. The role of generalized pain and pain behavior in tender point scores in fibromyalgia. J Rheumatol 2000;27:1056–62. NIH Consensus Development Panel on Depression in Late Life: Diagnosis and treatment of depression in late life. JAMA 1992; 268: 1018–24. Nutt DJ, Glue P. The neurobiology of ECT: animal studies. In: Coffey CE, editor. The clinical science of electroconvulsive therapy. Washington: American Psychiatric Press; 1993. p. 213–34. OÕConnor MK, Knapp R, Husain M, et al. The influence of age on the response of major depression to electroconvulsive therapy. A C.O.R.E. Report. Am J Geriat Psychiat 2001;9:382–90. Okifuji A, Turk DC, Sherman JJ. Evalution of the relationships between depression and fibromyalgia syndrome: why arenÕt all patients depressed? J Rheumatol 2000;27:212–9. OÕMalley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL. Treatment of fibromyalgia with antidepressants: a metaanalysis. J Gen Int Med 2000;15:659–66. Pisetsky J. The disappearance of painful phantom limbs after electric shock treatment. Am J Psychiat 1946;102:599–601. Prudic J, Haskett RF, Mulsant B, et al. Resistance to antidepressant medications and short-term clinical response to ECT. Am J Psychiat 1996;153:985–92. Rai SR, Broulillard D, Simson CS, Hopman WM, Abdollah H. Dysautonomia among patients with fibromyalgia: a noninvasive assessment. J Rheumatol 2000;27:2660–5. Rasmussen KG, Rummans TA. Electroconvulsive therapy for phantom limb pain. Pain 2000;85:297–9. Richards S, Cleare A. Fibromyalgia: biological correlates. Curr Opin Psychiat 2000;13:623–8. Sackeim HA, Prudic J, Devanand DP, et al. A prospective, randomised, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiat 2000;57:425–34. Salmon JB, Hanna MH, Williams M, Toone B, Wheeler M. Thalamic pain – the effect of electroconvulsive therapy. Pain 1988;33:67–71. Sameshima T, Doi N, Mera H, et al. Electroconvulsive therapy reduces pain in postherpetic neuralgia. Abstracts, 9th world congress on pain. Seattle: IASP Press; 1999. p. 191.
376
M.J. Huuhka et al. / European Journal of Pain 8 (2004) 371–376
Swartz CM, Abrams R. ECT instruction manual. 6th ed. Lake Bluff, IL: Somatics Inc.; 1996. The Practice of Electroconvulsive Therapy. Recommendations for treatment, training, and privileging. A Task Force Report of the American Psychiatric Association. Washington DC: American Psychiatric Association (APA); 2001. Thomson ME, Barkhuizen A. Fibromyalgia, hepatitis C infection, and the cytocine connection. Curr Pain Headache Rep 2003;7:342–7. Walker EA, Keegan D, Gardner G, Sullivan M, Katon WJ, Bernstein D. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: l. Psychiatric diagnosis and functional disability. Psychosom Med 1997;59:567–71.
Van Houdenhove B. Fibromyalgia a challenge for modern medicine [editorial]. Clin Rheumatol 2003;22:1–5. White KP, Speechley M, Harth M, Ostbye T. The London fibromyalgia epidemiology study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol 1999;26: 1570–6. White KP, Harth M. Classification, epidemiology and natural history of fibromyalgia. Curr Pain Headache Rep 2001;4:320–9. Wolfe F, Smythe HA, Yunus MG, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–72.