丸田俊彦：痛みと心身医学．心身医学 32: 97-103, 1992.
細井昌子、久保千春：疼痛性障害．痛みと臨床 4(4): 289-295, 2004.
高橋三郎、大野裕、染矢俊幸訳：DSM-IV-TR精神疾患の診断・統計マニュアル．医学書院、東京、2002.
本田哲三、中島恵子：認知行動療法的アプローチ．痛みと臨床 1 (3): 306-310, 2001.
本田哲三、中島恵子、水品朋子ほか：疼痛患者のリハビリテーション医療における教育・指導—慢性疼痛管理プログラムを中心に—．ペインクリニック 23: 1234-1242, 2002.
丸田俊彦：高齢者の慢性疼痛．老年精神医学雑誌 15: 312-316, 2004.
Gaby Bleichhardt, Barbara Timmer, Winfried Rief
Cognitive-behavioural therapy for patients with multiple somatoform symptoms--a randomised controlled trial in tertiary care.
J Psychosom Res. 2004 Apr;56(4):449-54. doi: 10.1016/S0022-3999(03)00630-5.
Abstract/Text
OBJECTIVE: (a) To evaluate the effect of a cognitive-behavioural inpatient treatment and (b) to analyse the differential efficacy of an additional ("soma") group management training of somatisation.
METHODS: The final sample consisted of 191 patients with somatisation syndrome (patients with at least eight DSM-IV somatoform symptoms). Patients were randomly assigned to (I) "standard treatment + soma" or (II) "standard treatment + relaxation training." A waiting control group consisted of 34 patients. All patients were diagnosed with a structured clinical interview for DSM-IV and received an interview on medical consulting behaviour and questionnaires concerning somatoform symptoms, general psychopathology, subjective health status, and life satisfaction.
RESULTS: Results show high impairment of the sample prior to treatment. At the 1-year follow-up, all outcome criteria were significantly reduced. The differential effect of the additional soma treatment was significant only for a reduction of visits to the doctor. Greatest longitudinal effect sizes were found for the reduction of somatoform symptoms.
CONCLUSION: Considering the subjects' high initial impairment, the outcome results are encouraging. The specific effect on health care use highlights the socioeconomic relevance.
Copyright 2004 Elsevier Inc.
Athula Sumathipala
What is the evidence for the efficacy of treatments for somatoform disorders? A critical review of previous intervention studies.
Psychosom Med. 2007 Dec;69(9):889-900. doi: 10.1097/PSY.0b013e31815b5cf6.
Abstract/Text
OBJECTIVE: To review published literature for the highest level of evidence on the efficacy of treatment for patients with medically unexplained symptoms.
METHODS: A comprehensive literature search was carried out in Cochrane library, Medline (1971-2007), PsychINFO (1974-2006), and EMBASE (1980-2007) to identify pharmacological, nonpharmacological, psychological, and other interventions, using the search terms "medically unexplained symptoms," "somatisation," "somatization," "somatoform disorders," "psychological therapies," "cognitive behavior therapy," "pharmacological therapies," "management," "therapy," "drug therapy," and "anti-depressants" with Boolean operators AND and OR on the entire text. Searches were confined to literature in English.
RESULTS: Studies were carried out in primary, secondary, and tertiary care settings. The therapists ranged from medical specialists, psychiatrists, and psychologists to primary care physicians. Three types of interventions (antidepressant medication, cognitive behavioral therapy (CBT), and other nonspecific interventions) were supported by evidence on the efficacy of treatment for patients with medically unexplained symptoms. There is more level I evidence for CBT compared with the amount for other approaches. There was only one study reported from the developing world.
CONCLUSIONS: CBT is efficacious for either symptom syndromes or for the broader category of medically unexplained symptoms, reducing physical symptoms, psychological distress, and disability. A relatively small number of studies were carried out in primary care, but the trend has been changing over the last decade. No studies have compared pharmacological and psychological treatments. Most trials assessed only short-term outcomes. Use of divergent selection procedures, interventions, outcome measures, and instruments, and other methodological differences observed in these studies hamper the ability to compare treatment effects across studies.
仙波純一：持続性身体表現性障害、疼痛性障害（慢性疼痛）．精神科治療学 26（増刊）: 161-169, 2011.
細井昌子：疼痛性障害．最新医学別冊 新しい診断と治療のABC 心身症（久保千春編）．最新医学社、2013.
Maria Kleinstäuber, Michael Witthöft, Andrés Steffanowski, Harm van Marwijk, Wolfgang Hiller, Michael J Lambert
Pharmacological interventions for somatoform disorders in adults.
Cochrane Database Syst Rev. 2014 Nov 7;(11):CD010628. doi: 10.1002/14651858.CD010628.pub2. Epub 2014 Nov 7.
Abstract/Text
BACKGROUND: Somatoform disorders are characterised by chronic, medically unexplained physical symptoms (MUPS). Although different medications are part of treatment routines for people with somatoform disorders in clinics and private practices, there exists no systematic review or meta-analysis on the efficacy and tolerability of these medications. We aimed to synthesise to improve optimal treatment decisions.
OBJECTIVES: To assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain disorder) in adults.
SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014). This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). To identify ongoing trials, we searched ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation & Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference proceedings and reference lists of potentially relevant papers and systematic reviews and contacted experts in the field.
SELECTION CRITERIA: We selected RCTs or cluster RCTs of pharmacological interventions versus placebo, treatment as usual, another medication, or a combination of different medications for somatoform disorders in adults. We included people fulfilling standardised diagnostic criteria for somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, or somatoform pain disorder.
DATA COLLECTION AND ANALYSIS: One review author and one research assistant independently extracted data and assessed risk of bias. Primary outcomes included the severity of MUPS on a continuous measure, and acceptability of treatment.
MAIN RESULTS: We included 26 RCTs (33 reports), with 2159 participants, in the review. They examined the efficacy of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products (NPs). The duration of the studies ranged between two and 12 weeks.One meta-analysis of placebo-controlled studies showed no clear evidence of a significant difference between tricyclic antidepressants (TCAs) and placebo for the outcome severity of MUPS (SMD -0.13; 95% CI -0.39 to 0.13; 2 studies, 239 participants; I(2) = 2%; low-quality evidence). For new-generation antidepressants (NGAs), there was very low-quality evidence showing they were effective in reducing the severity of MUPS (SMD -0.91; 95% CI -1.36 to -0.46; 3 studies, 243 participants; I(2) = 63%). For NPs there was low-quality evidence that they were effective in reducing the severity of MUPS (SMD -0.74; 95% CI -0.97 to -0.51; 2 studies, 322 participants; I(2) = 0%).One meta-analysis showed no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD -0.16; 95% CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42%; low-quality evidence). There was also no difference between NGAs and other NGAs for severity of MUPS (SMD -0.16; 95% CI -0.45 to 0.14; 4 studies, 182 participants; I(2) = 0%).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95% CI 0.32 to 1.22; 2 studies, 107 participants; I(2) = 23%).Differences regarding the acceptability of the treatment (rate of all-cause drop-outs) were neither found between NGAs and placebo (RR 1.01, 95% CI 0.64 to 1.61; 2 studies, 163 participants; I(2) = 0%; low-quality evidence) or NPs and placebo (RR 0.85, 95% CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0%; low-quality evidence); nor between TCAs and other medication (RR 1.48, 95% CI 0.59 to 3.72; 8 studies, 556 participants; I(2) =14%; low-quality evidence); nor between antidepressants and the combination of an antidepressant and an antipsychotic (RR 0.80, 95% CI 0.25 to 2.52; 2 studies, 118 participants; I(2) = 0%; low-quality evidence). Percental attrition rates due to adverse effects were high in all antidepressant treatments (0% to 32%), but low for NPs (0% to 1.7%).The risk of bias was high in many domains across studies. Seventeen trials (65.4%) gave no information about random sequence generation and only two (7.7%) provided information about allocation concealment. Eighteen studies (69.2%) revealed a high or unclear risk in blinding participants and study personnel; 23 studies had high risk of bias relating to blinding assessors. For the comparison NGA versus placebo, there was relatively high imprecision and heterogeneity due to one outlier study. Although we identified 26 studies, each comparison only contained a few studies and small numbers of participants so the results were imprecise.
AUTHORS' CONCLUSIONS: The current review found very low-quality evidence for NGAs and low-quality evidence for NPs being effective in treating somatoform symptoms in adults when compared with placebo. There was some evidence that different classes of antidepressants did not differ in efficacy; however, this was limited and of low to very low quality. These results had serious shortcomings such as the high risk of bias, strong heterogeneity in the data, and small sample sizes. Furthermore, the significant effects of antidepressant treatment have to be balanced against the relatively high rates of adverse effects. Adverse effects produced by medication can have amplifying effects on symptom perceptions, particularly in people focusing on somatic symptoms without medical causes. We can only draw conclusions about short-term efficacy of the pharmacological interventions because no trial included follow-up assessments. For each of the comparisons where there were available data on acceptability rates (NGAs versus placebo, NPs versus placebo, TCAs versus other medication, and antidepressants versus a combination of an antidepressant and an antipsychotic), no clear differences between the intervention and comparator were found.Future high-quality research should be carried out to determine the effectiveness of medications other than antidepressants, to compare antidepressants more thoroughly, and to follow-up participants over longer periods (the longest follow up was just 12 weeks). Another idea for future research would be to include other outcomes such as functional impairment or dysfunctional behaviours and cognitions as well as the classical outcomes such as symptom severity, depression, or anxiety.
Nikki van Dessel, Madelon den Boeft, Johannes C van der Wouden, Maria Kleinstäuber, Stephanie S Leone, Berend Terluin, Mattijs E Numans, Henriëtte E van der Horst, Harm van Marwijk
Non-pharmacological interventions for somatoform disorders and medically unexplained physical symptoms (MUPS) in adults.
Cochrane Database Syst Rev. 2014 Nov 1;(11):CD011142. doi: 10.1002/14651858.CD011142.pub2. Epub 2014 Nov 1.
Abstract/Text
BACKGROUND: Medically unexplained physical symptoms (MUPS) are physical symptoms for which no adequate medical explanation can be found after proper examination. The presence of MUPS is the key feature of conditions known as 'somatoform disorders'. Various psychological and physical therapies have been developed to treat somatoform disorders and MUPS. Although there are several reviews on non-pharmacological interventions for somatoform disorders and MUPS, a complete overview of the whole spectrum is missing.
OBJECTIVES: To assess the effects of non-pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform disorders unspecified, somatoform autonomic dysfunction, pain disorder, and alternative somatoform diagnoses proposed in the literature) and MUPS in adults, in comparison with treatment as usual, waiting list controls, attention placebo, psychological placebo, enhanced or structured care, and other psychological or physical therapies.
SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to November 2013. This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library, EMBASE, MEDLINE, and PsycINFO. We ran an additional search on the Cochrane Central Register of Controlled Trials and a cited reference search on the Web of Science. We also searched grey literature, conference proceedings, international trial registers, and relevant systematic reviews.
SELECTION CRITERIA: We included RCTs and cluster randomised controlled trials which involved adults primarily diagnosed with a somatoform disorder or an alternative diagnostic concept of MUPS, who were assigned to a non-pharmacological intervention compared with usual care, waiting list controls, attention or psychological placebo, enhanced care, or another psychological or physical therapy intervention, alone or in combination.
DATA COLLECTION AND ANALYSIS: Four review authors, working in pairs, conducted data extraction and assessment of risk of bias. We resolved disagreements through discussion or consultation with another review author. We pooled data from studies addressing the same comparison using standardised mean differences (SMD) or risk ratios (RR) and a random-effects model. Primary outcomes were severity of somatic symptoms and acceptability of treatment.
MAIN RESULTS: We included 21 studies with 2658 randomised participants. All studies assessed the effectiveness of some form of psychological therapy. We found no studies that included physical therapy.Fourteen studies evaluated forms of cognitive behavioural therapy (CBT); the remainder evaluated behaviour therapies, third-wave CBT (mindfulness), psychodynamic therapies, and integrative therapy. Fifteen included studies compared the studied psychological therapy with usual care or a waiting list. Five studies compared the intervention to enhanced or structured care. Only one study compared cognitive behavioural therapy with behaviour therapy.Across the 21 studies, the mean number of sessions ranged from one to 13, over a period of one day to nine months. Duration of follow-up varied between two weeks and 24 months. Participants were recruited from various healthcare settings and the open population. Duration of symptoms, reported by nine studies, was at least several years, suggesting most participants had chronic symptoms at baseline.Due to the nature of the intervention, lack of blinding of participants, therapists, and outcome assessors resulted in a high risk of bias on these items for most studies. Eleven studies (52% of studies) reported a loss to follow-up of more than 20%. For other items, most studies were at low risk of bias. Adverse events were seldom reported.For all studies comparing some form of psychological therapy with usual care or a waiting list that could be included in the meta-analysis, the psychological therapy resulted in less severe symptoms at end of treatment (SMD -0.34; 95% confidence interval (CI) -0.53 to -0.16; 10 studies, 1081 analysed participants). This effect was considered small to medium; heterogeneity was moderate and overall quality of the evidence was low. Compared with usual care, psychological therapies resulted in a 7% higher proportion of drop-outs during treatment (RR acceptability 0.93; 95% CI 0.88 to 0.99; 14 studies, 1644 participants; moderate-quality evidence). Removing one outlier study reduced the difference to 5%. Results for the subgroup of studies comparing CBT with usual care were similar to those in the whole group.Five studies (624 analysed participants) assessed symptom severity comparing some psychological therapy with enhanced care, and found no clear evidence of a difference at end of treatment (pooled SMD -0.19; 95% CI -0.43 to 0.04; considerable heterogeneity; low-quality evidence). Five studies (679 participants) showed that psychological therapies were somewhat less acceptable in terms of drop-outs than enhanced care (RR 0.93; 95% CI 0.87 to 1.00; moderate-quality evidence).
AUTHORS' CONCLUSIONS: When all psychological therapies included this review were combined they were superior to usual care or waiting list in terms of reduction of symptom severity, but effect sizes were small. As a single treatment, only CBT has been adequately studied to allow tentative conclusions for practice to be drawn. Compared with usual care or waiting list conditions, CBT reduced somatic symptoms, with a small effect and substantial differences in effects between CBT studies. The effects were durable within and after one year of follow-up. Compared with enhanced or structured care, psychological therapies generally were not more effective for most of the outcomes. Compared with enhanced care, CBT was not more effective. The overall quality of evidence contributing to this review was rated low to moderate.The intervention groups reported no major harms. However, as most studies did not describe adverse events as an explicit outcome measure, this result has to be interpreted with caution.An important issue was that all studies in this review included participants who were willing to receive psychological treatment. In daily practice, there is also a substantial proportion of participants not willing to accept psychological treatments for somatoform disorders or MUPS. It is unclear how large this group is and how this influences the relevance of CBT in clinical practice.The number of studies investigating various treatment modalities (other than CBT) needs to be increased; this is especially relevant for studies concerning physical therapies. Future studies should include participants from a variety of age groups; they should also make efforts to blind outcome assessors and to conduct follow-up assessments until at least one year after the end of treatment.
辻貞俊, 牛田享宏, 新井健一, 末冨勝敏, 西原真理, 池本竜則, 柿木隆介, 岡田和将, 野寺裕之, 村上正人, 比嘉和夫, 齋藤洋一,日本神経治療学会治療指針作成委員会：日本神経治療学会 標準的神経治療：慢性疼痛．神経治療学 27巻4号 Page591-622, 2010.
久保千春ほか：慢性疼痛．心身症診断・治療ガイドライン2006（小牧元・久保千春・福士審編）．協和企画、2006.
慢性疼痛治療ガイドライン作成ワーキンググループ編：慢性疼痛治療ガイドライン、真興交易医書出版部、2018.
慢性疼痛診療ガイドライン作成ワーキンググループ編：慢性疼痛診療ガイドライン、真興交易医書出版部、2021.
David A Fishbain, R B Cutler, John Lewis, Brandly Cole, R Steele Rosomoff, H L Rosomoff
Do the second-generation "atypical neuroleptics" have analgesic properties? A structured evidence-based review.
Pain Med. 2004 Dec;5(4):359-65. doi: 10.1111/j.1526-4637.2004.04054.x.
Abstract/Text
STUDY DESIGN: This is a structured, evidence-based review of all available studies on the potential effectiveness of the atypical neuroleptics for the treatment of pain (analgesia). To determine what evidence, if any, exists for, or against, the effectiveness of the atypical neuroleptics for analgesia.
SUMMARY OF BACKGROUND DATA: There has been significant controversy over whether the conventional neuroleptics (non-atypicals) have analgesic properties. A recent review (Patt et al. 1994) did conclude that the evidence for effectiveness was sparse, except for methotrimeprazine. However, that review did not include a new class of neuroleptics: the atypicals such as olazapine, risperidone, quetiapine, etc.
METHODS: A computer and manual search for studies relating to the atypicals and their analgesic effectiveness produced 10 studies/reports. These were reviewed in detail, and information relating to the above problem was abstracted and placed into tabular form. Each report was also categorized by the type of study it represented according to the guidelines developed by the Agency for Health Care Policy and Research (AHCPR). The strength and consistency of the evidence represented by the 10 studies were then categorized according to the AHCPR guidelines. Conclusions of this review were based on these results.
RESULTS OF DATA SYNTHESIS: Of the 10 studies/reports, four were characterized by AHCPR guidelines as Type II (experimental), two were Type III (quasiexperimental), two were Type IV (nonexperimental), and two were Type V (case reports). Of these studies/reports, 90% indicated that the atypicals did have an analgesic effect. The overall strength and consistency of this evidence using the AHCPR guidelines was, therefore, categorized as B (generally consistent from Type II, Type III, and Type IV studies).
CONCLUSIONS: Based on the above results, it was concluded that the reviewed data were generally consistent, suggesting that some of the atypicals may have an analgesic effect. There were, however, few double-blind, placebo-controlled studies, and many of the reports/studies had less than 50 patients. As such, this question requires further research.
細井昌子：心因性慢性疼痛．治療 90 (7): 2063-2072, 2008.
八反丸健二、増田彰則、中山高史ほか：慢性疼痛患者に対する多面的治療と経過について．心身医学 44: 194-200, 2004.
稲垣卓司、川向哲也、宇谷悦子、堀口淳：持続性身体表現性疼痛障害．精神科治療学 20（増刊）: 192-193, 2005.
P G O'Malley, J L Jackson, J Santoro, G Tomkins, E Balden, K Kroenke
Antidepressant therapy for unexplained symptoms and symptom syndromes.
J Fam Pract. 1999 Dec;48(12):980-90.
Abstract/Text
OBJECTIVE: To determine the efficacy of antidepressant therapy for unexplained symptoms or symptom syndromes.
SEARCH STRATEGIES: We identified original studies through searching MEDLINE, EMBASE, PsycLIT, the Federal Research in Progress database, and The Cochrane Library. We also searched the bibliographies of primary and review articles for additional studies.
SELECTION CRITERIA: We excluded trials of patients with neuropathic, oncologic, or degenerative joint pain. Independent duplicate review of 392 articles identified 94 relevant reports of randomized trials involving 6595 patients across 6 symptom syndromes. Independent duplicate assessment was made for inclusion and data abstraction. Meta-analysis was performed on extractable placebo-controlled data.
MAIN RESULTS: Of 94 included trials, most studied either tricyclic antidepressants, antiserotonin antidepressants, selective serotonin reuptake inhibitors (SSRIs), or multiple agents for the treatment of the following syndromes: headache (50), fibromyalgia (18), functional gastrointestinal syndromes (13), idiopathic pain (11), tinnitus (2), and chronic fatigue (2). The quality of the studies was fair (mean score = 4.8 on a scale of 0 to 8). A majority of the studies (69%) demonstrated benefit for at least one outcome measure. Symptom improvement typically did not correlate with depression response in the few studies where it was assessed. Meta-analysis of all extractable data showed a substantial benefit from antidepressants: For the dichotomous outcome of improvement, the odds ratio was 3.4 (95% confidence interval [CI], 2.6 - 4.5), and for continuous outcomes, the standardized mean difference was 0.87 (95% CI, 0.59-1.14). The absolute percentage difference in improvement between the antidepressant and placebo arms was 32%, yielding a number needed to treat of 3 to improve one person's symptoms. Meta-regression indicated no differential effect across the classes of antidepressants; however, onbivariate tally tricyclic studies were associated with a greater likelihood of efficacy than SSRI studies (P = .02).
CONCLUSIONS: Antidepressants can be effective for various physical symptoms and symptom syndromes. The relation of outcome to depression and the efficacy of SSRIs needs further study.
Juan A Micó, Denis Ardid, Esther Berrocoso, Alain Eschalier
Antidepressants and pain.
Trends Pharmacol Sci. 2006 Jul;27(7):348-54. doi: 10.1016/j.tips.2006.05.004. Epub 2006 Jun 9.
Abstract/Text
Tricyclic antidepressants, together with anticonvulsants, are considered to be first-line drugs for the treatment of neuropathic pain. Antidepressants are analgesic in patients with chronic pain and no concomitant depression, indicating that the analgesic and antidepressant effects occur independently. The analgesia induced by these drugs seems to be centrally mediated but consistent evidence also indicates a peripheral site of action. Several pharmacological mechanisms account for their antinociceptive effect but the inhibition of monoamine transporters (and, consequently, the facilitation of descending inhibition pain systems) is implicated on the basis of mechanistic and knockout-mouse studies. However, pain is a common symptom of depression, and depression is frequent in chronic pain patients, supporting the hypothesis that pain and depression share some common biochemical mechanisms. We suggest that antidepressants have a genuine analgesic effect and that research into their mechanisms of action will help to facilitate the development of new drugs.
