今日の臨床サポート

全般性不安障害/全般不安症

著者: 越野 好文 医療法人社団澄鈴会 アイリス メディカル クリニック

監修: 上島国利 昭和大学

著者校正/監修レビュー済:2017/03/31
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 全般性不安障害(GAD)/全般不安症とは、過剰な不安と特定のテーマに限局されない心配(予期憂慮)が6カ月間以上続くことを特徴とする精神科疾患である。
  1. 地域住民における1年有病率は0.4~3.6%で、生涯有病率は4~9%といわれ、決してまれな病気ではない。
  1. 身体症状を愁訴にプライマリケア医を受診する患者が多い。
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  1. 全般性不安障害(GAD)/全般不安症患者の約90%に他の精神疾患が共存(併存)し、特にうつ病は全般性不安障害(GAD)/全般不安症患者の2/3に合併する。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
越野 好文 : 特に申告事項無し[2021年]
監修:上島国利 : 原稿料(大日本住友製薬)[2021年]

病態・疫学・診察

疾患情報  
  1. 全般性不安障害(GAD)/全般不安症の患者は過剰な不安と心配(予期憂慮)がほとんど毎日続くことが特徴である。
  1. 米国精神医学会の診断マニュアルDSM-5[1]( 解説 )によれば
  1. A.(仕事や学業などの)多数の出来事または活動についての過剰な不安と心配(予期憂慮)が、起こる日のほうが起こらない日より多い状態が、少なくとも6カ月間にわたる。
  1. B.その人は、その心配を抑制することが難しいと感じている
  1. C.その不安および心配は、以下の6つの症状のうち3つ(またはそれ以上)を伴っている(過去6カ月間、少なくとも数個の症状が、起こる日のほうが起こらない日より多い)。
注:子どもの場合は1項目だけが必要
  1. (1)落ち着きのなさ、緊張感、または神経の高ぶり
  1. (2)疲労しやすいこと
  1. (3)集中困難、または心が空白になること
  1. (4)易怒性
  1. (5)筋肉の緊張
  1. (6)睡眠障害(入眠または睡眠維持の困難、または、落ちつかず熟眠感のない睡眠)
  1. D.その不安、心配、または身体症状が、臨床的に意味のある苦痛、または社会的、職業的、または他の重要な領域における機能の障害を引き起こしている。
  1. E.その障害は、物質(例:乱用薬物、医薬品)または他の医学的疾患(例:甲状腺機能亢進症)の生理学的作用によるものではない。
  1. F.その障害は他の精神疾患ではうまく説明されない(例:パニック症におけるパニック発作が起こることの不安または心配、社交不安症[社交恐怖]における否定的評価、強迫症における汚染または、他の強迫観念、分離不安症における愛着の対象からの分離、心的外傷後ストレス障害における身体的訴え、醜形恐怖症における想像上の外見上の欠点の知覚、病気不安症における深刻な病気をもつこと、または、統合失調症または妄想性障害における妄想的信念の内容、に関する不安または心配)
(出典:DSM-5 精神疾患の診断・統計マニュアル.医学書院, 2014; 220-221)
  1. 地域住民における1年有病率は0.4~3.6%で、生涯有病率は4~9%といわれ、決してまれな病気ではない[1][2]。 解説 
  1. 身体症状を愁訴にプライマリケア医を受診する患者が多く[3]、時点有病率は8%との報告がある[4]。 解説  解説 
  1. 臨床場面では女性が男性の約2倍である[1]
問診・診察のポイント  
  1. 現在の不安症状を評価すると同時に、過去の類似の症状を確認する。

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文献 

著者: Bridget F Grant, Deborah S Hasin, Frederick S Stinson, Deborah A Dawson, W June Ruan, Risë B Goldstein, Sharon M Smith, Tulshi D Saha, Boji Huang
雑誌名: Psychol Med. 2005 Dec;35(12):1747-59. doi: 10.1017/S0033291705006069. Epub 2005 Oct 5.
Abstract/Text BACKGROUND: This study addressed the prevalences, correlates, co-morbidity and disability of DSM-IV generalized anxiety disorder (GAD) and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The study presents nationally representative data, for the first time, on prevalence, correlates, co-morbidity, and comparative disability of DSM-IV GAD.
METHOD: Data are taken from a large (n=43093) representative sample of the adult USA population.R: Prevalences of 12-month and lifetime GAD were 2.1% and 4.1%. Being female, middle-aged, widowed/separated/divorced, and low income increased risk, while being Asian, Hispanic, or Black decreased risk. GAD was highly co-morbid with substance use, and other anxiety, mood, and personality disorders. Co-morbidity in GAD was not substantially greater than for most other Axis I and II disorders. Disability and impairment in pure GAD were equivalent to pure mood disorders, but significantly greater than in pure substance use, and other anxiety and personality disorders. Individuals co-morbid for GAD and each mood disorder were more disabled than those with pure forms of GAD or each mood disorder. When co-morbid with GAD, nicotine dependence and other anxiety and personality disorders were not associated with increased disability over that associated with pure GAD, but GAD did show increased disability over that due to each of these disorders in pure form.Conclusions. Associations between GAD and Axis I and II disorders were strong and significant, with variation among specific disorders. Results strongly support GAD as an independent disorder with significant impairment and disability.

PMID 16202187  Psychol Med. 2005 Dec;35(12):1747-59. doi: 10.1017/S003・・・
著者: H U Wittchen, J Hoyer
雑誌名: J Clin Psychiatry. 2001;62 Suppl 11:15-9; discussion 20-1.
Abstract/Text Generalized anxiety disorder (GAD) is a chronic and highly prevalent disorder in the adult population, yet it remains a relatively poorly understood condition. Clinicians may be familiar with the symptoms of enduring excessive worrying, anxiety, and hypervigilance that are characteristic of GAD, but may not necessarily recognize that these are usually symptoms of a distinct psychiatric disorder. Despite changes in diagnostic criteria, estimates of prevalence for GAD are remarkably consistent across epidemiologic studies. Lifetime prevalence in the general population is estimated at 5% (DSM-III and/or DSM-III-R criteria), with rates as high as 10% among women aged 40 years and above, and cross-sectional rates among primary care attenders are about 8%, making GAD the most prevalent anxiety disorder in primary care. The age at onset of GAD differs from that of other anxiety disorders: prevalence rates are low in adolescents and young adults but increase substantially with age. Females are at greater risk than males, and the disorder is correlated with being unemployed or a housewife or having a chronic medical illness. GAD is frequently associated with comorbid depression and other anxiety and somatoform disorders. Significant GAD-specific disability occurs even when comorbidity is not present.

PMID 11414546  J Clin Psychiatry. 2001;62 Suppl 11:15-9; discussion 20・・・
著者: Robert L Spitzer, Kurt Kroenke, Janet B W Williams, Bernd Löwe
雑誌名: Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
Abstract/Text BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity.
METHODS: A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use.
RESULTS: A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale.
CONCLUSION: The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.

PMID 16717171  Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.10・・・
著者: T J Meyer, M L Miller, R L Metzger, T D Borkovec
雑誌名: Behav Res Ther. 1990;28(6):487-95.
Abstract/Text The present report describes the development of the Penn State Worry Questionnaire to measure the trait of worry. The 16-item instrument emerged from factor analysis of a large number of items and was found to possess high internal consistency and good test-retest reliability. The questionnaire correlates predictably with several psychological measures reasonably related to worry, and does not correlate with other measures more remote to the construct. Responses to the questionnaire are not influenced by social desirability. The measure was found to significantly discriminate college samples (a) who met all, some, or none of the DSM-III-R diagnostic criteria for generalized anxiety disorder and (b) who met criteria for GAD vs posttraumatic stress disorder. Among 34 GAD-diagnosed clinical subjects, the worry questionnaire was found not to correlate with other measures of anxiety or depression, indicating that it is tapping an independent construct with severely anxious individuals, and coping desensitization plus cognitive therapy was found to produce significantly greater reductions in the measure than did a nondirective therapy condition.

PMID 2076086  Behav Res Ther. 1990;28(6):487-95.
著者: A S Zigmond, R P Snaith
雑誌名: Acta Psychiatr Scand. 1983 Jun;67(6):361-70.
Abstract/Text A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.

PMID 6880820  Acta Psychiatr Scand. 1983 Jun;67(6):361-70.
著者: David S Baldwin, Sarah Waldman, Christer Allgulander
雑誌名: Int J Neuropsychopharmacol. 2011 Jun;14(5):697-710. doi: 10.1017/S1461145710001434. Epub 2011 Jan 7.
Abstract/Text Generalized anxiety disorder (GAD) is common in community and clinical settings. The associated individual and societal burden is substantial, but many of those who could benefit from treatment are not recognized or treated. This paper reviews the pharmacological treatment of GAD, based on findings of randomized placebo-controlled studies. Particular attention is paid to response rates to acute treatment, treatment tolerability, prediction of response, duration of treatment, and further management of patients who do not respond to initial treatment approaches. On the basis of their proven efficacy and reasonable tolerability in randomized placebo-controlled trials, recent evidence-based guidelines for pharmacological management have recommended initial treatment with either a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor, although there is also good evidence for the efficacy of pregabalin and quetiapine. It is difficult to predict reliably which patients will respond well to pharmacological treatment, but response to antidepressants is unlikely if there is no evidence of an onset of effect within 4 wk. The small number of placebo-controlled relapse-prevention studies causes uncertainty about the optimal duration of treatment after a satisfactory initial response, but continuing treatment for at least 12 months is recommended. There have been few investigations of the further management of patients who have not responded to first-line treatment, but switching to another evidence-based treatment, or augmentation approaches may be beneficial.

PMID 21211105  Int J Neuropsychopharmacol. 2011 Jun;14(5):697-710. doi・・・
著者: Jonathan R Davidson
雑誌名: J Clin Psychiatry. 2009;70 Suppl 2:25-31.
Abstract/Text Many patients with generalized anxiety disorder (GAD) do not receive adequate treatment. Several classes of drugs, including benzodiazepines, azapirones, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, antihistamines, alpha(2)delta Ca++ channel modulators, and atypical antipsychotics are consistently beneficial in patients with GAD. Cognitive therapy is also effective as a first-line treatment. When individualizing treatment, drug dose ranges and side effect profiles need to be considered, as well as the patient's comorbid conditions. Doses may need to be reduced for elderly or medically ill patients or those taking other medications. Doses may need to be increased for refractory cases. Common comorbid conditions with GAD include depression, alcohol or drug abuse, social anxiety disorder, and panic disorder. In patients with significant depression, an antidepressant is more likely to succeed than a benzodiazepine. Generalized anxiety disorder is a chronic illness that requires long-term treatment. Remission is attainable but can take several months, and stopping medication increases the risk of relapse within the first year of initiating treatment.

Copyright 2009 Physicians Postgraduate Press, Inc.
PMID 19371504  J Clin Psychiatry. 2009;70 Suppl 2:25-31.
著者: Peter Tyrer, David Baldwin
雑誌名: Lancet. 2006 Dec 16;368(9553):2156-66. doi: 10.1016/S0140-6736(06)69865-6.
Abstract/Text Generalised anxiety disorder is a persistent and common disorder, in which the patient has unfocused worry and anxiety that is not connected to recent stressful events, although it can be aggravated by certain situations. This disorder is twice as common in women than it is in men. Generalised anxiety disorder is characterised by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. These symptoms are recognised as part of the anxiety syndrome rather than independent complaints. The symptoms overlap greatly with those of other common mental disorders and we could regard the disorder as part of a spectrum of mood and related disorders rather than an independent disorder. Generalised anxiety disorder has a relapsing course, and intervention rarely results in complete resolution of symptoms, but in the short term and medium term, effective treatments include psychological therapies, such as cognitive behavioural therapy; self-help approaches based on cognitive behavioural therapy principles; and pharmacological treatments, mainly selective serotonin reuptake inhibitors.

PMID 17174708  Lancet. 2006 Dec 16;368(9553):2156-66. doi: 10.1016/S01・・・
著者: Rosario B Hidalgo, Larry A Tupler, Jonathan R T Davidson
雑誌名: J Psychopharmacol. 2007 Nov;21(8):864-72. doi: 10.1177/0269881107076996.
Abstract/Text Generalized anxiety disorder (GAD) is a prevalent and impairing disorder, associated with extensive psychiatric and medical comorbidity and usually characterized by a chronic course. Different drugs have been investigated in GAD; among them are the following: 1) SSRIs: paroxetine, sertraline, fluvoxamine and escitalopram; 2) SNRI1s: venlafaxine; 3) benzodiazepines (BZs): alprazolam, diazepam and lorazepam; 4) azapirones (AZAs): buspirone; 5) antihistamines (AHs): hydroxyzine; 6) pregabalin (PGB); and 7) complementary/alternative medicine (CAM): kava-kava and homeopathic preparation. We conducted an effect size (ES) analysis of 21 double-blind placebo-controlled trials of medications treating DSM-III-R, DSM-IV or ICD-10 GAD using HAM-A change in score from baseline or endpoint score as the main efficacy measure. Literature search was performed using MEDLINE and PsycINFO databases including articles published between 1987 and 2003 and personal communications with investigators and sponsors. comparing all drugs versus placebo, the ES was 0.39. Mean ESs, excluding children, were PGB: 0.50, AH: 0.45, SNRI: 0.42, BZ: 0.38, SSRI: 0.36, AZA: 0.17 and CAM: -0.31. Comparing ES for adults versus children/adolescents (excluding CAM) and conventional drugs versus CAM (excluding children/adolescents) we found significantly higher ES for children/adolescents and for conventional drugs (p < 0.001 and p < 0.01, respectively). No significant differences were found when comparing date of publication, location of site (i.e. US versus other), fixed versus flexible dosing, number of study arms, or number of outcome measures used. Medications varied in the magnitude of their ES, ranging from moderate to poor. Adolescents and children showed a much greater ES compared with adults. Subjects taking CAM had worse outcomes than placebo.

PMID 17984162  J Psychopharmacol. 2007 Nov;21(8):864-72. doi: 10.1177/・・・
著者: David Baldwin, Robert Woods, Richard Lawson, David Taylor
雑誌名: BMJ. 2011 Mar 11;342:d1199. Epub 2011 Mar 11.
Abstract/Text OBJECTIVE: To appraise the evidence for comparative efficacy and tolerability of drug treatments in patients with generalised anxiety disorder.
DESIGN: Systematic review of randomised controlled trials. Primary Bayesian probabilistic mixed treatment meta-analyses allowed pharmacological treatments to be ranked for effectiveness for each outcome measure, given as percentage probability of being the most effective treatment. Secondary frequentist mixed treatment meta-analyses conducted with random effects model; effect size reported as odds ratio and 95% confidence interval.
DATA SOURCES: Medline, Embase, BIOSIS, PsycINFO, Health Economic Evaluations Database, National Health Service Economic Evaluation Database, and Database of Abstracts of Reviews of Effects via DataStar, and Cochrane Database of Systematic Reviews via Cochrane Library (January 1980 to February 2009). Eligibility criteria Double blind placebo controlled randomised controlled trials; published systematic reviews and meta-analyses of randomised controlled trials. Randomised controlled trials including adult participants (aged ≥ 18) receiving any pharmacological treatment for generalised anxiety disorder. Data abstraction methods Titles or abstracts reviewed initially, followed by review of full text publications for citations remaining after first pass. A three person team conducted screening; an independent reviewer checked a random selection (10%) of articles screened. Data extracted for meta-analysis were also independently reviewed.
MAIN OUTCOME MEASURES: Proportion of participants experiencing ≥ 50% reduction from baseline score on Hamilton anxiety scale (HAM-A) (response), proportion with final HAM-A score ≤ 7 (remission), proportion withdrawing from trial because of adverse events (tolerability).
RESULTS: The review identified 3249 citations, and 46 randomised controlled trials met inclusion criteria; 27 trials contained sufficient or appropriate data for inclusion in the analysis. Analyses compared nine drugs (duloxetine, escitalopram, fluoxetine, lorazepam, paroxetine, pregabalin, sertraline, tiagabine, and venlafaxine). In the primary probabilistic mixed treatment meta-analyses, fluoxetine was ranked first for response and remission (probability of 62.9% and 60.6%, respectively) and sertraline was ranked first for tolerability (49.3%). In a subanalysis ranking treatments for generalised anxiety disorder currently licensed in the United Kingdom, duloxetine was ranked first for response (third across all treatments; 2.7%), escitalopram was ranked first for remission (second across all treatments; 26.7%), and pregabalin was ranked first for tolerability (second across all treatments; 7.7%).
CONCLUSIONS: Though the frequentist analysis was inconclusive because of a high level of uncertainty in effect sizes (based on the relatively small number of comparative trials), the probabilistic analysis, which did not rely on significant outcomes, showed that fluoxetine (in terms of response and remission) and sertraline (in terms of tolerability) seem to have some advantages over other treatments. Among five UK licensed treatments, duloxetine, escitalopram, and pregabalin might offer some advantages over venlafaxine and paroxetine.

PMID 21398351  BMJ. 2011 Mar 11;342:d1199. Epub 2011 Mar 11.
著者: P Rocca, V Fonzo, M Scotta, E Zanalda, L Ravizza
雑誌名: Acta Psychiatr Scand. 1997 May;95(5):444-50.
Abstract/Text Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.

PMID 9197912  Acta Psychiatr Scand. 1997 May;95(5):444-50.
著者: K Rickels, E Schweizer
雑誌名: J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):101S-110S.
Abstract/Text Evidence suggests that generalized anxiety disorder (GAD) has a fairly chronic course marked by significant long-term distress and comorbidity. Research has focused on short-term treatment of GAD, and long-term outcome studies after either short- or long-term treatment have been relatively neglected. The authors discuss the benefits and risks of various drug and nondrug therapies used in the long-term management of generalized anxiety disorder and suggest avenues for future research.

PMID 1973934  J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):101S-110S.・・・

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