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心臓神経症

著者: 稲光哲明 にゅうわ会及川病院 心療内科

監修: 今井靖 自治医科大学 薬理学講座臨床薬理学部門・内科学講座循環器内科学部門

著者校正/監修レビュー済:2020/01/17
患者向け説明資料

概要・推奨   

  1. 胸痛を主訴に循環器科を受診する患者の30~60%は心臓神経症である。一方で、正確な診断がつけられず、専門的な治療を受けられないまま経過している患者が多い(O、推奨度2)。
  1. 胸痛を主訴とする患者で心臓神経症を積極的に疑う症例としては、若い女性で強い不安を訴えて多彩な自律神経症状を伴っている場合である。器質的心疾患患者との不安の違いは、心臓への注意集中と症状に対する不安の程度が強いことである(O、推奨度2)。
  1. 冠動脈疾患患者でも不安やうつを伴うことが多く、不安やうつは冠動脈疾患のリスク因子であり、合併症であり、予後不良因子であることから治療介入が必要となる(O、推奨度2)。
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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:
稲光哲明 : 特に申告事項無し[2021年]
監修:今井靖 : 講演料(第一三共株式会社)[2021年]

改訂のポイント:
  1. 定期レビューを行い、以下の点について一部改訂を行った。
  1. BZDは睡眠薬としても、抗不安薬としても、即効性、有効性、安全性の面から、現在でも汎用されている薬剤である。しかし、最近、本剤の長期間投与により、たとえその使用量が適正であっても、精神依存や身体依存が形成されることが問題となってきた。さらに、転倒・骨折のリスク、認知機能低下のリスク、せん妄誘発のリスクなども懸念されており、BZDの安易な長期の処方を避けるべきであると注意喚起が下された。すでに、平成26年にBZDを含む向精神薬の多剤併用に保険診療上の規制が実施されていたが、平成30年にはBZDの漫然とした長期処方に規制が加えられている。
  1. これまで心臓神経症の治療薬として、SSRIと同等の重要な薬剤として扱われていたBZDだが、その使用法を制限するとともに、使用に際しての注意や患者への教育が必要となった。一方で、一般心理療法の重要性がさらに強まってきている。
  1. 今回の改定では、そうした診療面の実情に合わせて、すでに発表された類縁疾患のガイドラインをもとに作成した治療のアルゴリズムを改訂した。
  1. 今後、BZDの使用は控える方向になると考えられるので、それに代わる、重症例に対する治療法や、現在すでにBZDを使用中の患者に対する減量法などについて、エビデンスが揃い次第追加していく。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 心臓神経症は、胸痛や動悸などの心血管系愁訴があるものの、それを説明するだけの器質的疾患が認められない場合に診断する。広義には、器質的疾患や不整脈などを伴っていても、患者の訴える症状が明らかに強い場合も含まれる[1]
  1. 心臓神経症の定義:表<図表>
  1. 不安を基調とする神経症圏の病態を「心臓神経症」、体質的素因が強く自律神経に基づく身体症状が強い病態を「神経循環無力症」と区別する考え方もある[1]
  1. 上のような病態に対して歴史的にはさまざまな病名が報告されてきた。「ダ・コスタ症候群」、「努力症候群」、「過敏心」、「兵隊心」、「戦争神経症」、「神経循環無力症」などの病名は戦時中の兵士で報告された病名であり、「自律神経失調症」、「機能性心血管障害」、「多動心症候群」「β-アドレナリン性高心拍出性循環状態」は自律神経機能異常、特に交感神経機能亢進状態に注目した病名である。その他に、「神経衰弱症」、「不安神経症」の病名は精神面での疲労や不安に焦点を当てた病名である。
 
  1. 現在、「心臓神経症」の病名は用いられることが少なくなり、「パニック症」「双極性障害および関連障害群」「抑うつ障害群」「身体症状症および関連症群」「病気不安症」などのDSM-5の診断名がそれぞれの診断基準で用いられている[2]
  1. 心臓神経症に相当する精神障害の種類とその診断基準(要約)と治療:表<図表>
  1. ICD-10では、「身体表現性自律神経機能不全」 の「心臓および血管系の項目」として、ダ・コスタ症候群や神経循環無力症とともに「心臓神経症」が挙げられている[3][4]が、パニック症やうつ病などによる心血管系の症状を呈する場合を含めて考えるのが一般的である[1]
  1. ICD-10にみられる心臓神経症の診断ガイドライン(診断: >詳細情報 「DSM-5による精神障害の評価:」参照)
  1. 一方で、心筋梗塞や心不全などの重症心疾患では死の恐怖から、心臓神経症が起こりやすい。
  1. 心臓に対する病的関心(とらわれ)の度合いには、心臓病を過度に心配して通常の病状説明では納得しない症例(病気不安症)から、妄想的に心臓病を確信しており修正が困難な症例(妄想性障害-身体型)もある[2]
  1. 病前性格、心身疲労やストレス、心理的葛藤、死への不安が病態に関与しており、不安中枢(扁桃核)と自律神経交感神経中枢(視床下部)の神経興奮状態が病気の本態と考えられる。
 
心臓神経症の成立機序(森田療法の神経症理論による)

心臓神経症の発症には、準備因子、発症(誘発)因子、持続・増悪因子がある。準備因子としては、性格、幼少時の分離不安体験、現実生活での慢性的な心理的ストレスがあり、発症因子には、急性の身体的または精神的ストレスによる偶発的な初発症状がある。
こうしていったん発症すると、不安と症状の悪循環(精神交互作用と呼ばれている)が形成されて、心臓神経症が完成することになる。そして、この悪循環は持続、増悪因子となる。長期間の悪循環の持続は、うつ状態を引き起こして、社会生活、日常生活、職業的生活が営めなくなり、疾患が固定化して難治性となる。
 
参考文献:
稲光哲明:パニック障害.久保千春,中井吉英,野添新一編.現代心療内科学.永井書店,2003;510.

出典

 
  1. 心臓神神経症の頻度は不明であるが、代表的な類縁疾患であるパニック症については、生涯有病率で1~3%、胸痛で救急部を受診する患者の17~25%であり、循環器専門の診療科における外来患者の30~60%が心臓神経症やうつ病であるといわれる。年齢では思春期より30歳代前半までが多く、そのほかに中年期にも1つの山がある。女性が男性の2倍多い[5][6]
  1. 慢性になると社会生活が営めなくなって難治化しやすい。重症うつ病や薬物依存などを合併してくる[5][6]
 
  1. 心臓神経症においては交感神経機能が亢進した状態にある(O)。
  1. パニック症をはじめとする不安症患者の自律神経機能が検討されている。
  1. 安静時における差については議論があるが[7]、実験的ストレス負荷時には、心拍数の上昇[8][9]、血圧の上昇[10]、血中エピネフリンの増加[7]、心拍変動の低下[9]、心拍変動スペクトル解析における中周波成分(一般には低周波成分に入る領域)の上昇[11]などが報告されている。このことから、パニック症では少なくともストレス下では交感神経機能が亢進し、副交感神経機能が減弱していることが考えられる。
  1. 追記:心臓神経症では、ストレスを受けたときに交感神経機能が亢進し、副交感神経が減弱した状態にある。
 
  1. 胸痛を主訴に循環器科を受診する患者の30~60%は心臓神経症である。一方で、正確な診断がつけられず、専門的な治療を受けられないまま経過している患者が多い(O、推奨度2)。
  1. 胸痛を訴える患者の30~40%は、心血管系の疾患ではなく心臓神経症(文献ではパニック症や恐怖症)やうつ病と診断される[12][13]
  1. 循環器科ならびに救急外来で胸痛を主訴として来院する患者のうち、約25~57%がパニック症とみられている[14][15][16]
  1. しかし、多くの患者は循環器検査を受けても診断がつかないため、非定型胸痛、非心臓性胸痛、非狭心症性胸痛などと診断名がつけられて[17]、一般的な循環器治療が続けられており、心臓神経症(文献ではパニック症、うつ病、恐怖症などの精神障害)を疑われて専門医を紹介される症例は少なく、したがって適切な治療を受けられないまま、複数の循環器専門医を訪れて、同一の循環器系検査を複数回受けている患者が多い[14][18]
  1. 追記:胸痛などの心血管系愁訴がある患者に、心臓神経症(できればDSM-5による精神障害)の診断がつけられて、適切な治療が開始されることが望まれる。
問診・診察のポイント  
  1. 身体症状、すなわち動悸、息切れ、胸痛、胸部不快感、めまい、疲労感、発汗、ふるえ、頻脈など自律神経を中心とした症状の有無について聴取する。

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文献 

著者: Peter Ham, David B Waters, M Norman Oliver
雑誌名: Am Fam Physician. 2005 Feb 15;71(4):733-9.
Abstract/Text Panic disorder with or without agoraphobia occurs commonly in patients in primary care settings. This article assesses multiple evidence-based reviews of effective treatments for panic disorder. Antidepressant medications successfully reduce the severity of panic symptoms and eliminate panic attacks. Selective serotonin reuptake inhibitors and tricyclic antidepressants are equally effective in the treatment of panic disorder. The choice of medication is based on side effect profiles and patient preferences. Strong evidence supports the effectiveness of cognitive behavior therapy in treating panic disorder. Family physicians who are not trained in cognitive behavior therapy may refer patients with panic disorder to therapists with such training. Cognitive behavior therapy can be used alone or in combination with antidepressants to treat patients with panic disorder. Benzodiazepines are effective in treating panic disorder symptoms, but they are less effective than antidepressants and cognitive behavior therapy.

PMID 15742911  Am Fam Physician. 2005 Feb 15;71(4):733-9.
著者: David Austin, Grant Blashki, David Barton, Britt Klein
雑誌名: Aust Fam Physician. 2005 Jul;34(7):563-71.
Abstract/Text BACKGROUND: Panic disorder (PD) is common in the community and contributes to significant distress and decreased quality of life for people who suffer from it. Most people with PD will present in the first instance to their general practitioner or hospital emergency department for assistance, often with a focus on somatic symptoms and concerns.
OBJECTIVE: This article aims to assist the GP to manage this group of patients by providing an outline of aetiology, approaches to assessment, and common management strategies. DISCUSSION Although GPs have an important role to play in ruling out any causal organic basis for panic symptoms, the diagnosis of PD can usually be made as a positive diagnosis on the basis of careful history taking. Thorough and empathic education is a vital step in management. The prognosis for PD can be improved by lifestyle changes, specific psychological techniques, and the judicious use of pharmacotherapy.

PMID 15999167  Aust Fam Physician. 2005 Jul;34(7):563-71.
著者: D J Wilkinson, J M Thompson, G W Lambert, G L Jennings, R G Schwarz, D Jefferys, A G Turner, M D Esler
雑誌名: Arch Gen Psychiatry. 1998 Jun;55(6):511-20. doi: 10.1001/archpsyc.55.6.511.
Abstract/Text BACKGROUND: The sympathetic nervous system has long been believed to be involved in the pathogenesis of panic disorder, but studies to date, most using peripheral venous catecholamine measurements, have yielded conflicting and equivocal results. We tested sympathetic nervous function in patients with panic disorder by using more sensitive methods.
METHODS: Sympathetic nervous and adrenal medullary function was measured by using direct nerve recording (clinical microneurography) and whole-body and cardiac catecholamine kinetics in 13 patients with panic disorder as defined by the DSM-IV, and 14 healthy control subjects. Measurements were made at rest, during laboratory stress (forced mental arithmetic), and, for 4 patients, during panic attacks occurring spontaneously in the laboratory setting.
RESULTS: Muscle sympathetic activity, arterial plasma concentration of norepinephrine, and the total and cardiac norepinephrine spillover rates to plasma were similar in patients and control subjects at rest, as was whole-body epinephrine secretion. Epinephrine spillover from the heart was elevated in patients with panic disorder (P=.01). Responses to laboratory mental stress were almost identical in patient and control groups. During panic attacks, there were marked increases in epinephrine secretion and large increases in the sympathetic activity in muscle in 2 patients but smaller changes in the total norepinephrine spillover to plasma.
CONCLUSIONS: Whole-body and regional sympathetic nervous activity are not elevated at rest in patients with panic disorder. Epinephrine is released from the heart at rest in patients with panic disorder, possibly due to loading of cardiac neuronal stores by uptake from plasma during surges of epinephrine secretion in panic attacks. Contrary to popular belief, the sympathetic nervous system is not globally activated during panic attacks.

PMID 9633669  Arch Gen Psychiatry. 1998 Jun;55(6):511-20. doi: 10.100・・・
著者: M B Stein, M E Tancer, T W Uhde
雑誌名: Arch Gen Psychiatry. 1992 Apr;49(4):311-7. doi: 10.1001/archpsyc.49.4.311.
Abstract/Text Heart rate and plasma norepinephrine responsivity to a physiologic challenge, ie, orthostasis, were measured in 20 patients with panic disorder (PD) and 20 age- and sex-matched normal control subjects. While the two groups exhibited similar supine heart rates, patients with PD had a significantly greater heart rate response to orthostatic challenge. Plasma norepinephrine responses did not differ between patients with PD and normal control subjects. In a matched subgroup of 14 patients with PD, 14 normal control subjects, and 14 patients with social phobia, the patients with social phobia exhibited supine and upright plasma norepinephrine levels that were significantly higher than those of the other two diagnostic groups. Taken together, and in the context of findings from other studies, these preliminary observations suggest that the anxiety disorders may demonstrate differing patterns of autonomic dysfunction.

PMID 1558465  Arch Gen Psychiatry. 1992 Apr;49(4):311-7. doi: 10.1001・・・
著者: B H Friedman, J F Thayer
雑誌名: Biol Psychol. 1998 Nov;49(3):303-23. doi: 10.1016/s0301-0511(98)00051-9.
Abstract/Text Autonomic characteristics of panickers, blood phobics, and nonanxious controls were compared with a variety of cardiovascular measures, including spectral analysis of the cardiac inter-beat interval time series (derived from the electrocardiogram). Responses to laboratory stressors (shock avoidance and cold face stress) of 16 participants who reported recent occurrences of frequent severe panic attacks, 15 participants who reported strong somatic reactions and fainting to the sight of blood, and 15 controls, were recorded. Results suggested distinct autonomic patterns among the three groups. Across conditions, panickers displayed the highest heart rates (HR) coupled with the least HR variability, which indicates low levels of cardiac vagal tone. Blood phobics showed more vagally mediated HR variability than panickers, with a significant association between cardiac rate and mean arterial pressure. Controls generally showed the most HR variability and 'spectral reserve' (a quality that indicates flexible responsivity). Results are discussed in the context of traditional models of anxiety and autonomic activity in contrast to contemporary notions of stability and change in biological systems.

PMID 9858059  Biol Psychol. 1998 Nov;49(3):303-23. doi: 10.1016/s0301・・・
著者: Nick J Coupland, Susan J Wilson, John P Potokar, Caroline Bell, David J Nutt
雑誌名: Psychiatry Res. 2003 May 1;118(1):69-79. doi: 10.1016/s0165-1781(03)00045-3.
Abstract/Text Although autonomic function has been investigated in panic disorder (PD), previous studies have not used non-invasive beat by beat blood pressure (BP) monitoring to assess the rapid dynamics of BP during autonomic reflex tests. The hypothesis of the current study was that patients with PD would show increased cardiovascular sympathetic reactivity compared with healthy or anxious controls, as assessed by the initial overshoot of diastolic BP during the immediate response to standing. Patients with PD (n=56), social phobia (n=28) and healthy volunteers (n=56) were tested using finger photoplethysmography during an orthostatic challenge. Panic disorder patients showed an increased BP overshoot compared with both control groups. Moreover, in a preliminary assessment of selective serotonin reuptake inhibitor treatment effects, the BP overshoot was significantly reduced towards normal values. These findings are consistent with recent evidence for increased sympathetic baroreflex function in PD and may be relevant to the pathophysiology of the disorder.

PMID 12759163  Psychiatry Res. 2003 May 1;118(1):69-79. doi: 10.1016/s・・・
著者: V K Yeragani, R Pohl, R Berger, R Balon, C Ramesh, D Glitz, K Srinivasan, P Weinberg
雑誌名: Psychiatry Res. 1993 Jan;46(1):89-103. doi: 10.1016/0165-1781(93)90011-5.
Abstract/Text We have previously found decreased standard deviations and mean consecutive differences of R-R intervals in panic disorder patients in standing posture, compared with control subjects. In the present study, we used spectral analysis of heart rate variability to examine autonomic function in 21 panic disorder patients and 21 normal control subjects. Patients had a significantly lower standard deviation of heart rate in supine as well as standing postures. Absolute low frequency power (0.01-0.05 Hz) was also significantly lower in panic disorder patients in standing postures. Upon standing, the panic disorder patients had significantly higher relative mid-frequency power (0.07-0.15 Hz). During a standing deep-breathing condition at six breaths per minute, the patients had a significantly decreased absolute and relative mid-frequency (0.07-0.15 Hz) power compared with control subjects. These findings suggest a decrease in cholinergic and a relative increase in adrenergic responsiveness in panic disorder patients compared with control subjects.

PMID 8464959  Psychiatry Res. 1993 Jan;46(1):89-103. doi: 10.1016/016・・・
著者: K W Yingling, L R Wulsin, L M Arnold, G W Rouan
雑誌名: J Gen Intern Med. 1993 May;8(5):231-5. doi: 10.1007/bf02600087.
Abstract/Text OBJECTIVE: 1) To determine whether the frequencies of panic disorder (PD) and depression (DEP) in an emergency department (ED) population were comparable to those in other primary care groups; 2) to evaluate whether patients without the clinical diagnosis of acute cardiac ischemia (ACI) had higher frequencies of these disorders; and 3) to identify characteristic clinical findings in patients with PD or DEP.
SETTING: An urban teaching hospital ED.
PATIENTS: Three hundred thirty-four patients with acute chest pain were evaluated prospectively over an eight-week period. The cohort participating (69%-229/334) completed psychiatric screening measures, including the Panic Disorder Self-Rating Scale, the Beck Depression Inventory, and the Zung Self-Rating Anxiety Scale.
MEASUREMENTS AND MAIN RESULTS: A symptom profile consistent with PD was identified in 17.5% of the patients (40/229), DEP in 23.1% (53/229), and either disorder in 35% (80/229). The prevalences of PD were similar in those with and without ACI (19.4% vs 16.6%, respectively, p > 0.05). The likelihoods of one or more ED visits for chest pain in the previous year were significantly greater in those with PD (57.5% vs 36%, p < 0.05) and DEP (54% vs 35%, p < 0.05) than in those without these psychiatric disorders.
CONCLUSION: This study suggests that approximately one in three patients presenting to the ED with acute pain has symptoms consistent with a psychiatric disorder. These disorders occur frequently in both those with and those without acute cardiac ischemia, and clinical variables may help identify these frequent ED utilizers.

PMID 8505680  J Gen Intern Med. 1993 May;8(5):231-5. doi: 10.1007/bf0・・・
著者: W Katon, M L Hall, J Russo, L Cormier, M Hollifield, P P Vitaliano, B D Beitman
雑誌名: Am J Med. 1988 Jan;84(1):1-9. doi: 10.1016/0002-9343(88)90001-0.
Abstract/Text Seventy-four patients with chest pain and no prior history of organic heart disease were interviewed with a structured psychiatric interview immediately after coronary arteriography. The majority of patients with both negative and positive coronary angiographies had undergone previous exercise tolerance tests, but the patients with angiographic coronary artery disease were significantly more likely to have had positive results on a treadmill test. Patients with chest pain and negative coronary arteriograms were significantly younger; more likely to be female; more apt to have a higher number of autonomic symptoms (tachycardia, dyspnea, dizziness, and paresthesias) associated with chest pain, and more likely to describe atypical chest pain. Patients with chest pain and normal coronary arteriographic results also had significantly higher psychologic scores on indices of anxiety and depression and were significantly more likely to meet criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for panic disorder (43 percent versus 6.5 percent), major depression (36 percent versus 4 percent), and two or more phobias (36 percent versus 15 percent) than were patients with chest pain and a coronary arteriography study demonstrating coronary artery stenosis.

PMID 3337115  Am J Med. 1988 Jan;84(1):1-9. doi: 10.1016/0002-9343(88・・・
著者: Julia Anna Glombiewski, Winfried Rief, Stefan Bösner, Heidemarie Keller, Alexandra Martin, Norbert Donner-Banzhoff
雑誌名: Arch Intern Med. 2010 Feb 8;170(3):251-5. doi: 10.1001/archinternmed.2009.474.
Abstract/Text BACKGROUND: Nonspecific chest pain is common in primary care, yet knowledge is sparse about its course and outcome and how they relate to optimum health care usage. We investigated the following observations: (1) many patients who present with nonspecific chest pain in primary care show symptom persistence for 6 months, (2) many patients with nonspecific chest pain showed signs of overinvestigation, and (3) many patients with chronic chest pain were referred to mental health specialists.
METHODS: We conducted a prospective, general physician-based cohort study with 6-week and 6-month follow-ups in 74 primary care offices in Hessen, Germany. Of approximately 190 000 consecutive patients who visited their general physicians from October 1, 2005, to July 31, 2006, 807 patients with nonspecific chest pain were identified by an expert committee (delayed-type reference standard). The dropout rate was 2.7%. Main outcome measures were persistent chest pain at a 6-month follow-up visit and health care usage at 6 months.
RESULTS: The rate of persistent chest pain was 55.5%. A total of 10.7% of patients had inappropriate health care usage, defined as 2 or more visits to a cardiologist or 3 or more cardiac diagnostic investigations. Most patients with persistent nonspecific chest pain were referred to a cardiologist, and less than 2% were referred to mental health specialists.
CONCLUSIONS: For most patients with nonspecific chest pain, standard medical care does not offer sufficient help for symptom relief. One-tenth of patients with persistent chest pain underwent additional diagnostic testing of no known clinical benefit. Psychological referrals were rarely given.

PMID 20142569  Arch Intern Med. 2010 Feb 8;170(3):251-5. doi: 10.1001/・・・
著者: Jeff C Huffman, Mark H Pollack
雑誌名: Psychosomatics. 2003 May-Jun;44(3):222-36. doi: 10.1176/appi.psy.44.3.222.
Abstract/Text As many as 25% of patients with chest pain who come to hospital emergency departments have panic disorder. Rates of panic disorder are even higher among those who present for outpatient evaluation of their chest pain. Unfortunately, panic disorder remains largely undiagnosed and untreated in these settings. The authors reviewed studies published between 1970 and 2001 that addressed the prevalence of panic disorder among persons who seek treatment for chest pain in an emergency department or outpatient cardiology clinic. A meta-analysis of the findings revealed five variables that appear to correlate with higher rates of panic disorder among persons who present with chest pain: 1). absence of coronary artery disease, 2). atypical quality of chest pain, 3). female sex, 4). younger age, and 5). a high level of self-reported anxiety. Further studies of these and other variables associated with panic disorder should aid in the detection of this disabling but treatable cause of chest pain.

PMID 12724504  Psychosomatics. 2003 May-Jun;44(3):222-36. doi: 10.1176・・・
著者: R P Fleet, G Dupuis, A Marchand, J Kaczorowski, D Burelle, A Arsenault, B D Beitman
雑誌名: J Psychosom Res. 1998 Jan;44(1):81-90. doi: 10.1016/s0022-3999(97)00136-0.
Abstract/Text In this study we address the following questions: (1) What percentage of coronary artery disease (CAD) patients that present with chest pain, but whose symptoms cannot be fully explained by their cardiac status, suffer from panic disorder (PD)? (2) How do patients with both CAD and PD compare to patients without CAD and to patients without either PD or CAD in terms of psychological distress? Four hundred forty-one consecutive walk-in emergency department patients with chest pain underwent a structured psychiatric interview (ADIS-R) and completed psychological scales. Fifty-seven percent (250 of 441) of these patients were diagnosed as having noncardiac chest pain and constituted this study's sample. A total of 30% (74 of 250) of noncardiac chest pain patients had a documented history of CAD. Thirty-four percent (25 of 74) of CAD patients met criteria for PD. Patients with both PD and CAD displayed significantly more psychological distress than CAD patients without PD and patients with neither CAD nor PD. However, they did not differ from non-CAD patients with PD. PD is highly prevalent in patients with CAD that are discharged with noncardiac diagnoses. The psychological distress in these patients appears to be related to the panic syndrome and not to the presence of the cardiac condition.

PMID 9483466  J Psychosom Res. 1998 Jan;44(1):81-90. doi: 10.1016/s00・・・
著者: R P Fleet, G Dupuis, A Marchand, D Burelle, A Arsenault, B D Beitman
雑誌名: Am J Med. 1996 Oct;101(4):371-80. doi: 10.1016/S0002-9343(96)00224-0.
Abstract/Text PURPOSE: To establish the prevalence of panic disorder in emergency department (ED) chest pain patients; compare psychological distress and recent suicidal ideation in panic and non-panic disorder patients; assess psychiatric and cardiac comorbidity; and examine physician recognition of this disorder.
DESIGN: Cross-sectional survey (for psychiatric data). Prospective evaluation of patient discharge diagnoses and physician recognition of panic disorder.
SETTING: The ambulatory ED of a major teaching hospital specializing in cardiac care located in Montreal, Canada.
SUBJECTS: Four hundred and forty-one consenting, consecutive patients consulting the ED with a chief complaint of chest pain.
PRIMARY OUTCOME MEASURE: Psychiatric diagnoses (AXIS I). Psychological and pain test scores, discharge diagnoses, and cardiac history.
RESULTS: Approximately 25% (108/441) of chest pain patients met DSM-III-R criteria for panic disorder. Panic disorder patients displayed significantly higher panic-agoraphobia, anxiety, depression, and pain scores than non-panic disorder patients (P < 0.01). Twenty-five percent of panic disorder patients had thoughts of killing themselves in the week preceding their ED visit compared with 5% of the patients without this disorder (P = 0.0001) even when controlling for co-existing major depression. Fifty-seven percent (62/108) panic disorder patients also met criteria for one or more current AXIS I disorder. Although 44% (47/108) of the panic disorder patients had a prior documented history of coronary artery disease (CAD), 80% had atypical or nonanginal chest pain and 75% were discharged with a "noncardiac pain" diagnosis. Ninety-eight percent of the panic patients were not recognized by attending ED cardiologists.
CONCLUSIONS: Panic disorder is a significantly distressful condition highly prevalent in ED chest pain patients that is rarely recognized by physicians. Nonrecognition may lead to mismanagement of a significant group of distressed patients with or without coronary artery disease.

PMID 8873507  Am J Med. 1996 Oct;101(4):371-80. doi: 10.1016/S0002-93・・・
著者: T Dammen, H Arnesen, O Ekeberg, T Husebye, S Friis
雑誌名: J Intern Med. 1999 May;245(5):497-507. doi: 10.1046/j.1365-2796.1999.00447.x.
Abstract/Text OBJECTIVES: The aims of the study were to: (i) determine the prevalence of panic disorder (PD) in patients referred to cardiological outpatient clinics for evaluation of chest pain; (ii) compare psychiatric comorbidity, psychological distress, pain characteristics and suicidal ideation in PD and non-PD patients: (iii) compare the prevalence of coronary risk factors and medical comorbidity in PD and non-PD patients; and (iv) describe current PD treatment and need for PD treatment as expressed by PD patients.
DESIGN: A cross-sectional study based on psychiatric and cardiological investigation.
SETTING: Four cardiological outpatient clinics in Oslo, Norway.
SUBJECTS: One-hundred and ninety-nine consecutive patients without known heart disease referred to out-patient clinics for investigation of chest pain.
MAIN OUTCOME MEASURES: Psychiatric state diagnosis (axis I); scores on self-assessment rating scales of psychological factors and pain modalities; cardiological diagnosis.
RESULTS: Thirty-eight per cent of the patients met criteria for current panic disorder (PD). Panic disorder was associated with psychological distress, comorbid psychiatric disorders, medical disorders and significantly higher prevalence of coronary risk factors (P<0.05). Furthermore. the results suggest that these patients were not identified and appropriately treated for panic disorder prior to cardiological investigation. The results indicate that the patients are positive to screening for psychiatric disorder and communicate a need for treatment early in the investigation process.
CONCLUSION: PD commonly occurs in this chest pain population. Thus, there is a need to educate physicians caring for these patients about PD identification and treatment.

PMID 10363751  J Intern Med. 1999 May;245(5):497-507. doi: 10.1046/j.1・・・
著者: Craig D Marker, Cheryl N Carmin, Raymond L Ownby
雑誌名: Depress Anxiety. 2008;25(10):824-31. doi: 10.1002/da.20348.
Abstract/Text Many studies have shown that cardiac anxiety when occurring in the absence of coronary artery disease is common and quite costly. The Cardiac Anxiety Questionnaire (CAQ) is an 18-item self-report measure that assesses anxiety related to cardiac symptoms. To better understand the construct of cardiac anxiety, a factor analysis was conducted on CAQ data from 658 individuals who were self or physician-referred for electron beam tomographic screening to determine whether clinically significant coronary atherosclerosis was present. A four-factor solution was judged to provide the best fit with the results reflecting the following factor composition: heart-focused attention, avoidance of activities that bring on symptoms, worry or fear regarding symptoms, and reassurance-seeking. Factorial invariance across groups was also assessed to determine whether the factor structure of the CAQ was similar in individuals with and without clear evidence of coronary atherosclerosis. The factor structure of the CAQ did not differ between the two groups. However, the group without coronary atherosclerosis had significantly higher mean scores on their attention and worry/fear factors suggesting that people without a diagnosed cardiac condition pay more attention to and worry more about their cardiac-related symptoms than those people who have coronary atherosclerosis.

Depression and Anxiety 2007. Published 2007 Wiley-Liss, Inc.
PMID 17597101  Depress Anxiety. 2008;25(10):824-31. doi: 10.1002/da.20・・・
著者: B D Beitman, V Mukerji, J W Lamberti, L Schmid, L DeRosear, M Kushner, G Flaker, I Basha
雑誌名: Am J Cardiol. 1989 Jun 1;63(18):1399-403. doi: 10.1016/0002-9149(89)91056-4.
Abstract/Text Although patients with angiographically normal or near normal coronary arteries are at low risk for cardiac disease, several follow-up studies have shown that many continue to report recurrent chest pain associated with social and work dysfunction. Three diagnostic entities have been proposed to explain the morbidity of this group: microvascular angina, esophageal motility disorders and panic disorder. The purpose of this study was to test the hypothesis that panic disorder is found frequently in patients with chest pain who have normal epicardial vessels. Ninety-four subjects with angiographically normal coronary arteries were interviewed according to a structured psychiatric protocol within 24 hours of their catheterizations. Thirty-two (34%) fit Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) criteria for current panic disorder. Because panic disorder can be effectively treated, physicians should consider this diagnosis in this group of patients. Current research findings suggest that panic disorder, microvascular angina and esophageal disorders may each form the basis for chest pain in approximately 25% of these patients. Miscellaneous problems account for the other 25%.

PMID 2729113  Am J Cardiol. 1989 Jun 1;63(18):1399-403. doi: 10.1016/・・・
著者: R Fleet, K Lavoie, B D Beitman
雑誌名: J Psychosom Res. 2000 Apr-May;48(4-5):347-56. doi: 10.1016/s0022-3999(99)00101-4.
Abstract/Text OBJECTIVE: To critically review existing literature examining the relationship between panic disorder (PD) and coronary artery disease (CAD). We specifically sought answers to the following questions: (1) What is the prevalence of PD in CAD patients? (2) What is the directionality of the relationship between PD and CAD? (3) What mechanisms may mediate the link between PD and CAD?
METHODS: Medline and Psychlit searches were conducted using the following search titles: "panic disorder and coronary artery disease", "panic disorder and coronary heart disease", and "panic disorder and cardiovascular disease" for the years 1980-1998. The above search was also repeated replacing "panic disorder" with "panic attacks" for the same period.
RESULTS: The prevalence of PD in both cardiology out-patients and patients with documented CAD ranges from 10% to 50%. The association between PD and CAD appeared strongest in patients with atypical chest pain or symptoms that could not be fully explained by coronary status. There is some evidence linking phobic anxiety but not PD per se to CAD risk, but little evidence linking CAD to PD risk. Studies of the mechanisms linking PD to CAD are still in their infancy, but there is preliminary evidence linking PD to reduced heart rate variability (HRV) and myocardial ischemia, two pathophysiological mechanisms related to CAD.
CONCLUSION: PD is prevalent in CAD patients, but it is unclear the extent to which PD confers risk for and/or exacerbates CAD. Prospective research is needed to more firmly establish PD as a distinct risk factor for the development and progression of CAD. However, because many of the symptoms of PD mimic those of CAD, differentiating these disorders and learning how they may influence each other is imperative for clinical practice.

PMID 10880657  J Psychosom Res. 2000 Apr-May;48(4-5):347-56. doi: 10.1・・・
著者: A Rozanski, J A Blumenthal, J Kaplan
雑誌名: Circulation. 1999 Apr 27;99(16):2192-217. doi: 10.1161/01.cir.99.16.2192.
Abstract/Text Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

PMID 10217662  Circulation. 1999 Apr 27;99(16):2192-217. doi: 10.1161/・・・
著者: Judith H Lichtman, J Thomas Bigger, James A Blumenthal, Nancy Frasure-Smith, Peter G Kaufmann, François Lespérance, Daniel B Mark, David S Sheps, C Barr Taylor, Erika Sivarajan Froelicher, American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, American Heart Association Council on Clinical Cardiology, American Heart Association Council on Epidemiology and Prevention, American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research, American Psychiatric Association
雑誌名: Circulation. 2008 Oct 21;118(17):1768-75. doi: 10.1161/CIRCULATIONAHA.108.190769. Epub 2008 Sep 29.
Abstract/Text Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

PMID 18824640  Circulation. 2008 Oct 21;118(17):1768-75. doi: 10.1161/・・・
著者: M Valkamo, J Hintikka, L Niskanen, H Viinamäki
雑誌名: Acta Psychiatr Scand. 2001 Nov;104(5):391-6. doi: 10.1034/j.1600-0447.2001.00165.x.
Abstract/Text OBJECTIVE: To assess psychiatric morbidity in coronary angiogram patients.
METHOD: A psychiatric assessment of 200 consecutive chest-pain patients was performed the day before coronary angiography in a double-blind study design. The sample included 132 men (mean age 57.2 years, SD 9.5) and 68 women (mean age 59.8 years, SD 8.9). A Structured Clinical Interview for DSM-III-R was used to obtain psychiatric diagnosis. The 21-item Beck Depression Inventory, the 20-item Toronto Alexithymia Scale and a four-item Life Satisfaction Scale were used to assess mental symptoms. A coronary angiography with obstruction of a coronary artery by more than 50% was considered to indicate angiographic coronary disease.
RESULTS: Mental disorders were found in 28% (95% CI 14-41) of the patients with normal angiographic findings (n=47) and in 24% (95% CI 17 - 30) of the patients with angiographic coronary disease (n=153). Furthermore, no difference was found between these two groups in other rating scales assessing mental symptoms even when adjusted for the New York Heart Association class, duration of chest-pain symptoms or exercise capacity.
CONCLUSION: Psychiatric morbidity may not be associated with angiographic findings in patients with chest pain.

PMID 11722322  Acta Psychiatr Scand. 2001 Nov;104(5):391-6. doi: 10.10・・・
著者: D R Thompson, R J Lewin
雑誌名: Heart. 2000 Jul;84(1):101-5. doi: 10.1136/heart.84.1.101.
Abstract/Text
PMID 10862600  Heart. 2000 Jul;84(1):101-5. doi: 10.1136/heart.84.1.10・・・
著者: Cecilia A Essau, Judith Conradt, Franz Petermann
雑誌名: J Anxiety Disord. 2002;16(1):67-81. doi: 10.1016/s0887-6185(01)00091-3.
Abstract/Text The aim of this article was to examine the course and outcome of anxiety disorders in German adolescents. Anxiety and other psychiatric disorders were coded based on DSM-IV criteria using the computerized Munich version of the Composite International Diagnostic Interview. About 22.6% of the adolescents who fulfilled DSM-IV criteria of any current anxiety disorders at the index investigation (T1) continued to have anxiety at the follow-up investigation (T2), 17.7% had depression, 27.4% somatoform, 6.5% substance use disorders, and 41.9% had no disorders. The factors that were significantly associated with the persistence of anxiety disorders included older age, presence of somatoform and substance use disorders, as well as a high number of negative life events at the T1-interview. Adolescents with "chronic" compared to "transient" anxiety disorders and those without any disorders were significantly more impaired in various life domains. Despite these high levels of psychosocial impairment, only a few of them did seek professional help in the last 12 months before the T2-interview.

PMID 12171214  J Anxiety Disord. 2002;16(1):67-81. doi: 10.1016/s0887-・・・
著者: N M Batelaan, R de Graaf, B W J H Penninx, A J L M van Balkom, W A M Vollebergh, A T F Beekman
雑誌名: Psychol Med. 2010 Jan;40(1):147-57. doi: 10.1017/S0033291709005625. Epub 2009 Apr 29.
Abstract/Text BACKGROUND: Panic disorder (PD) is generally considered to be a chronic or intermittent disorder. This view may be biased because of a lack of general population studies investigating panic from the onset of an episode onwards. Data regarding the course of subthreshold panic disorder (sub-PD) and predictors of its course are lacking.
METHOD: Using data from a large community-based survey, the Netherlands Mental Health and Incidence Study (NEMESIS), that retrospectively assessed the 2-year course of panic with a Life Chart Interview (LCI), this study investigated remission, chronicity and recurrence in subjects with new episodes of PD or sub-PD. Predictor variables of remission consisted of sociodemographics, psychobiological, environmental, psychiatric and panic-related factors.
RESULTS: In PD, remission of panic attacks occurred in 64.5% of subjects, mean time to remission was 5.7 months, and the remission rate was 5.8/100 person-months. In 43.3% of subjects panic was still present after 1 year. Recurrence of panic attacks occurred in 21.4% of those with PD who had achieved remission and for whom sufficient follow-up time was available. In general, the course of sub-PD was more favourable. Predictors of remission were female gender, the absence of ongoing difficulties, subthreshold panic and a low initial frequency of attacks.
CONCLUSIONS: These results suggest that the course of panic is diverse in the general population, thereby underlining the need for accurate predictors. This requires further research including biological data and additional psychological data. In addition, given the large proportion with a relapse, relapse prevention should be part of any treatment programme.

PMID 19400975  Psychol Med. 2010 Jan;40(1):147-57. doi: 10.1017/S00332・・・
著者: C Faravelli, S Paterniti, A Scarpato
雑誌名: Compr Psychiatry. 1995 Jul-Aug;36(4):271-7. doi: 10.1016/s0010-440x(95)90072-1.
Abstract/Text Ninety-nine patients with panic disorder (PD) not comorbid with other psychiatric disorders were evaluated for 5 years using a naturalistic prospective design. The probability of achieving full remission, albeit transitory, was 37.5%, whereas 72.8% of cases showed a consistent amelioration. However, among patients with an initial positive outcome, the probability of remaining well was 41.4% after 5 years. When the general course of the disorder during the follow-up period was considered, only 12.12% of the subjects had a complete and stable remission of symptoms, whereas 47.47% had a generally positive but not fully satisfactory amelioration either due to infrequent recurrences of the illness or to chronic continuation of symptoms at a mild level. On the other hand, 40.40% of the subjects reported an overall poor outcome because of the presence of a recurrent pattern of illness (11.11%) or because the periods of well-being did not represent more than 40% of the time being considered (29.29%). Among the predictors taken into consideration, only duration of illness before intake showed a strict relationship with long-term outcome, with patients having a lesser duration of illness at the moment of the index episode showing a significantly better outcome.

PMID 7554871  Compr Psychiatry. 1995 Jul-Aug;36(4):271-7. doi: 10.101・・・
著者: D S Cowley, S N Flick, P P Roy-Byrne
雑誌名: Anxiety. 1996;2(1):13-21. doi: 10.1002/(SICI)1522-7154(1996)2:1<13::AID-ANXI2>3.0.CO;2-E.
Abstract/Text Fifty-five of 102 consecutively evaluated patients with panic disorder seen in consultation at a specialty anxiety and mood disorders clinic were reinterviewed from 15 to 60 months later after naturalistic treatment in the community. Over the follow-up period, most patients displayed improvement in panic attack frequency and severity, phobic avoidance, depression, and major role functioning, although only five (10%) were asymptomatic on all measures at follow-up. The majority of patients with impaired interpersonal functioning showed no improvement on this measure. Thirty percent of the patients were panic-free at 12 months and 28% at the time of follow-up, with 43% experiencing at least three panic-free months during the follow-up period. Comorbid agoraphobia, major depression, and Axis II disorders were associated with worse outcome on selected measures of symptomatic and functional impairment. However, the strongest predictors of overall improvement were avoidance coping for outcome at 12 months and Axis I comorbidity for outcome at the time of the follow-up evaluation.

PMID 9160594  Anxiety. 1996;2(1):13-21. doi: 10.1002/(SICI)1522-7154(・・・
著者: Jennifer L Francis, Risa B Weisberg, Ingrid R Dyck, Larry Culpepper, Kevin Smith, Maria Orlando Edelen, Martin B Keller
雑誌名: Prim Care Companion J Clin Psychiatry. 2007;9(3):173-9. doi: 10.4088/pcc.v09n0301.
Abstract/Text OBJECTIVE: To examine the course of panic disorder (PD) and panic disorder with agoraphobia (PDA) in 235 primary care patients during a 3-year period.
METHOD: Patients were recruited from primary care waiting rooms and diagnosed using the Structured Clinical Interview for DSM-IV. They were reassessed at 6 months, 1 year, and annually thereafter for diagnosis, treatment, and other clinical and demographic variables. Recruitment occurred between July 1997 and May 2001.
RESULTS: At intake, 85 patients were diagnosed with PD and 150 were diagnosed with PDA. Patients with PD were significantly more likely to achieve recovery (probability estimate, 0.75) from their disorder than patients with PDA (0.22) at the end of 3-year follow-up (p < .0001). There was no difference in recurrence rates between the 2 disorders. Women were more likely to recover from PD (p = .001). At intake, comorbid generalized anxiety disorder (p = .004), higher Global Assessment of Functioning score (p = .0003), and older age at panic onset (p = .05) were related to recovery from PDA, and comorbid major depressive disorder (p = .05) and psychosocial treatment (p = .002) predicted remaining in an episode of PDA. The relationship between psychosocial treatment and poor recovery must be interpreted with caution and is most likely due to the treatment bias effect.
CONCLUSION: Primary care patients with PDA have a chronic course of illness, whereas those with PD have a more relapsing course. Given the significant burden of PD and PDA in primary care, attention to factors relevant to the course of these disorders is important for recognition and for continued improvement of treatment interventions in this setting.

PMID 17632648  Prim Care Companion J Clin Psychiatry. 2007;9(3):173-9.・・・
著者: Holly J Ramsawh, Risa B Weisberg, Ingrid Dyck, Robert Stout, Martin B Keller
雑誌名: J Affect Disord. 2011 Jul;132(1-2):260-4. doi: 10.1016/j.jad.2011.01.006. Epub 2011 Feb 5.
Abstract/Text BACKGROUND: Age of onset is rarely studied in the anxiety disorders literature. The current study examined age of onset as it relates to clinical characteristics and course of anxiety disorders using a prospective, longitudinal, observational design.
METHODS: Fifteen-year follow-up data were examined for participants with panic disorder with (PDA) or without (PD) agoraphobia, social phobia (SP), and/or generalized anxiety disorder (GAD) at baseline. Logistic regression analyses were conducted to determine whether age of onset was associated with demographic or clinical variables at baseline. Cox regression analyses were conducted to examine longitudinal course (time to recurrence and recovery, respectively) for each diagnostic group.
RESULTS: At baseline, PD participants with early onset (i.e., < age 20) were more likely to have comorbid MDD, GAD, and SP relative to late-onset participants (≥ age 20). For PDA, early-onset participants were less likely to be married, and more likely to have both GAD and SP at baseline. With respect to longitudinal course, earlier onset was associated with an increased likelihood of recurrence in participants with PDA. No other models reached significance.
LIMITATIONS: The sample sizes for some disorders were comparatively small in relation to PDA, and all participants were treatment-seeking, which may limit generalizability.
CONCLUSIONS: For some anxiety disorders, earlier age of onset appears to be associated with greater severity and worse course, as evidenced by increased risk of recurrence over 15years of follow-up. Early interventions focused on children and adolescents may alleviate some of the public health burden associated with anxiety disorders.

Copyright © 2011 Elsevier B.V. All rights reserved.
PMID 21295858  J Affect Disord. 2011 Jul;132(1-2):260-4. doi: 10.1016/・・・
著者: Hemma Swoboda, M Amering, J Windhaber, H Katschnig
雑誌名: J Anxiety Disord. 2003;17(2):223-32. doi: 10.1016/s0887-6185(02)00183-4.
Abstract/Text BACKGROUND: The purpose of this study was to assess the naturalistic long-term course of panic disorder over a period of 11 years.
METHOD: Thirty DSM-III-R panic disorder patients, who had suffered from panic disorder for 6 years on average and who had taken part in an 8-week multicenter drug trial, were included in the intent-to-follow-up group to be reinterviewed 11 years after the end of the trial. At baseline and at follow-up the same instruments were used to assess frequency of panic attacks, level of phobic avoidance, and disabilities. Treatments received during the follow-up period and attempted suicides were assessed with a structured interview. Periods of well-being during the follow-up period were elicited retrospectively with a specifically designed longitudinal chart.
RESULTS: Twenty-four patients could actually be reinterviewed after 11.3 years. While at baseline all patients had suffered from panic attacks and had been severely disabled on a number of measures, 66.7% had no panic attack during the year before follow-up. During the month before follow-up 87.5% had no panic attack, and 54% showed no or only mild phobic avoidance. In the areas of work and family life 90% showed no or only mild disabilities, whereas in the area of social life this percentage was lower (67%). Thirty-three percent of the patients were completely remitted according to a composite remission criterion.
CONCLUSIONS: Panic disorder is not a uniformly chronic and progressing disorder. Over a period of 11 years there is a good chance of recovery from panic attacks and disabilities, and full remission is also possible.

PMID 12614664  J Anxiety Disord. 2003;17(2):223-32. doi: 10.1016/s0887・・・
著者: G A Fava, C Rafanelli, S Grandi, S Conti, C Ruini, L Mangelli, P Belluardo
雑誌名: Psychol Med. 2001 Jul;31(5):891-8. doi: 10.1017/s0033291701003592.
Abstract/Text BACKGROUND: There is a paucity of long-term outcome studies of panic disorder that exceed a 2-year follow-up. The aim of the study was to evaluate the long-term follow-up of patients with panic disorder with agoraphobia treated according to a standardized protocol.
METHODS: A consecutive series of 200 patients satisfying the DSM-IV criteria for panic disorder with agoraphobia was treated in an out-patient clinic with behavioural methods based on exposure homework. One hundred and thirty-six patients became panic free after 12 sessions of psychotherapy and 132 were available for follow-up. A 2- to 14-year (median = 8 years) follow-up was performed. Survival analysis was employed to characterize the clinical course of patients.
RESULTS: Thirty-one of the 132 patients (23%) had a relapse of panic disorder at some time during follow-up. The estimated cumulative percentage of patients remaining in remission was 93.1 after 2 years, 82.4 after 5 years, 78.8 after 7 years and 62.1 after 10 years. Such probabilities increased with younger age, and in the absence of a personality disorder, of high pre-treatment levels of depressed mood, of residual agoraphobic avoidance after exposure, and of concurrent use of benzodiazepines and antidepressant drugs.
CONCLUSIONS: The findings suggest that exposure treatment can provide lasting relief to the majority of patients with panic disorder and agoraphobia. Disappearance of residual and subclinical agoraphobic avoidance, and not simply of panic attacks, should be the aim of exposure therapy.

PMID 11459386  Psychol Med. 2001 Jul;31(5):891-8. doi: 10.1017/s003329・・・
著者: G A Clum, G A Clum, R Surls
雑誌名: J Consult Clin Psychol. 1993 Apr;61(2):317-26. doi: 10.1037//0022-006x.61.2.317.
Abstract/Text In a meta-analysis, the authors compared the effectiveness of psychological and pharmacological treatments for panic disorder. Percentage of agoraphobic subjects in the sample and duration of the illness were unrelated to effect size (ES). Type of dependent variable was generally unrelated to treatment outcome, although behavioral measures yielded significantly smaller ESs. Dependent measures of general anxiety, avoidance, and panic attacks yielded larger ESs than did depression measures. Choice of control was related to ES, with comparisons with placebo controls greater than comparisons with exposure-only or "other treatment" controls. Psychological coping strategies involving relaxation training, cognitive restructuring, and exposure yielded the most consistent ESs; flooding and combination treatments (psychological and pharmacological) yielded the next most consistent ESs. Antidepressants were the most effective pharmacological intervention.

PMID 8097212  J Consult Clin Psychol. 1993 Apr;61(2):317-26. doi: 10.・・・
著者: A Bakker, A J van Balkom, P Spinhoven, B M Blaauw, R van Dyck
雑誌名: J Nerv Ment Dis. 1998 Jul;186(7):414-9. doi: 10.1097/00005053-199807000-00005.
Abstract/Text We conducted a meta-analysis to update the knowledge of long-term efficacy of different treatments in panic disorder with or without agoraphobia. Included were 68 studies pertaining to 106 treatment conditions and 1346 patients. Effect sizes Cohen's d were calculated within the treatment conditions at posttest and at follow-up for panic and agoraphobia. A comparison was made between six treatments: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. The mean (+/- SD) duration of the follow-up period was 62 +/- 89 weeks. In the majority of the studies (84%), follow-up had a naturalistic character. The lack of information about treatments received between posttest and follow-up limits the interpretation of the results. For all conditions, the treatment gains at posttest were maintained during the follow-up period. The mean (+/- SD) d for panic was 1.11 +/- 0.70 at posttest and 1.28 +/- 0.61 at follow-up; for agoraphobia, the mean d at posttest was 1.36 +/- 1.10 and at follow-up it was 1.41 +/- 0.82. Significant differences were found in efficacy on agoraphobic measures at follow-up between the combination of antidepressants and exposure in vivo versus psychological panic management, exposure in vivo, and the combination of psychological panic management and exposure. Overall, the data suggest that different treatment options for panic disorder with or without agoraphobia are effective at both posttest and follow-up. Research on long-term treatment, discontinuation of therapies, and interventions between posttest and follow-up need more attention, for pharmacotherapy as well as psychotherapy.

PMID 9680042  J Nerv Ment Dis. 1998 Jul;186(7):414-9. doi: 10.1097/00・・・
著者: A J van Balkom, A Bakker, P Spinhoven, B M Blaauw, S Smeenk, B Ruesink
雑誌名: J Nerv Ment Dis. 1997 Aug;185(8):510-6. doi: 10.1097/00005053-199708000-00006.
Abstract/Text To compare short-term efficacy of benzodiazepines, antidepressants, psychological panic management, exposure in vivo, and combination treatments in panic disorder with or without agoraphobia (PA), a meta-analysis was conducted. Included were 106 studies, pertaining to 222 treatment conditions, 5,011 patients at pretest and 4,016 at posttest. Pre/post effect sizes Cohen's d were calculated within the treatment conditions for four clinical variables: panic, agoraphobia, depression, and general anxiety. Seven large treatment conditions were used in the main analyses: high-potency benzodiazepines, antidepressants, psychological panic management, exposure in vivo, pill-placebo combined with exposure, antidepressants combined with exposure, and psychological panic management combined with exposure in vivo. First, these treatments were compared with a control condition, consisting of pill-placebo, attention placebo, and waiting list. Next, a comparison was made between the treatments. Antidepressants, psychological panic management, high-potency benzodiazepines, and antidepressants combined with exposure in vivo were superior to the control condition for panic attacks. Exposure in vivo alone was not effective for panic attacks. With regard to agoraphobic avoidance, all seven treatments were superior to the control condition. When comparing the various treatment conditions, no differences concerning panic attacks were found. For agoraphobic avoidance, the combination of antidepressants with exposure in vivo was superior to the other conditions. The combination of antidepressants with exposure in vivo is the most potent short-term treatment of PA.

PMID 9284865  J Nerv Ment Dis. 1997 Aug;185(8):510-6. doi: 10.1097/00・・・
著者: Sue M Marcus, Jack Gorman, M Katherine Shear, David Lewin, Jose Martinez, Susan Ray, Raymond Goetz, Serge Mosovich, Lauren Gorman, David Barlow, Scott Woods
雑誌名: Am J Psychiatry. 2007 Feb;164(2):273-5. doi: 10.1176/ajp.2007.164.2.273.
Abstract/Text OBJECTIVE: The authors assessed whether adding cognitive behavior therapy (CBT) to imipramine for patients with panic disorder decreased the severity of side effects and dropouts from side effects.
METHOD: Data were analyzed for 172 panic disorder patients who were randomly assigned to receive imipramine alone, imipramine plus CBT, or placebo. Mixed-effects models were used to assess longitudinal differences among the treatment groups with respect to side effect burden and dropout rates during the acute, maintenance, and follow-up phases of treatment.
RESULTS: Patients treated with imipramine plus CBT experienced less severe fatigue/weakness, dry mouth, and sweating and had a lower rate of dropout due to side effects compared with those treated with imipramine only.
CONCLUSIONS: The addition of CBT to medication treatment with imipramine was associated with less severe side effects and fewer dropouts due to perceived side effects than treatment with imipramine alone.

PMID 17267790  Am J Psychiatry. 2007 Feb;164(2):273-5. doi: 10.1176/aj・・・
著者: D H Barlow, J M Gorman, M K Shear, S W Woods
雑誌名: JAMA. 2000 May 17;283(19):2529-36. doi: 10.1001/jama.283.19.2529.
Abstract/Text CONTEXT: Panic disorder (PD) may be treated with drugs, psychosocial intervention, or both, but the relative and combined efficacies have not been evaluated in an unbiased fashion.
OBJECTIVE: To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo, whether one treatment is more effective than the other, and whether combined therapy is more effective than either therapy alone.
DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998.
PATIENTS: A total of 312 patients with PD were included in the analysis.
INTERVENTIONS: Patients were randomly assigned to receive imipramine, up to 300 mg/d, only (n=83); cognitive-behavioral therapy (CBT) only (n=77); placebo only (n=24); CBT plus imipramine (n=65); or CBT plus placebo (n=63). Patients were treated weekly for 3 months (acute phase); responders were then seen monthly for 6 months (maintenance phase) and then followed up for 6 months after treatment discontinuation.
MAIN OUTCOME MEASURES: Treatment response based on the Panic Disorder Severity Scale (PDSS) and the Clinical Global Impression Scale (CGI) by treatment group.
RESULTS: Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS (response rates for the intent-to-treat [ITT] analysis, 45.8%, 48.7%, and 21.7%; P=.05 and P=.03, respectively), but were not significantly different for the CGI (48. 2%, 53.9%, and 37.5%, respectively). After 6 months of maintenance, imipramine and CBT were significantly more effective than placebo for both the PDSS (response rates, 37.8%, 39.5%, and 13.0%, respectively; P=.02 for both) and the CGI (37.8%, 42.1%, and 13.0%, respectively). Among responders, imipramine produced a response of higher quality. The acute response rate for the combined treatment was 60.3% for the PDSS and 64.1% for the CGI; neither was significantly different from the other groups. The 6-month maintenance response rate for combined therapy was 57.1% for the PDSS (P=.04 vs CBT alone and P=.03 vs imipramine alone) and 56.3% for the CGI (P=.03 vs imipramine alone), but not significantly better than CBT plus placebo in either analysis. Six months after treatment discontinuation, in the ITT analysis CGI response rates were 41.0% for CBT plus placebo, 31.9% for CBT alone, 19.7% for imipramine alone, 13% for placebo, and 26.3% for CBT combined with imipramine.
CONCLUSIONS: Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance. Each treatment worked well immediately following treatment and during maintenance; CBT appeared durable in follow-up. JAMA. 2000;283:2529-2536

PMID 10815116  JAMA. 2000 May 17;283(19):2529-36. doi: 10.1001/jama.28・・・
著者: T A Furukawa, N Watanabe, R Churchill
雑誌名: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004364. doi: 10.1002/14651858.CD004364.pub2. Epub 2007 Jan 24.
Abstract/Text BACKGROUND: Panic disorder can be treated with pharmacotherapy, psychotherapy or in combination, but the relative merits of combined therapy have not been well established.
OBJECTIVES: To review evidence concerning short- and long-term advantages and disadvantages of combined psychotherapy plus antidepressant treatment for panic disorder with or without agoraphobia, in comparison with either therapy alone.
SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 11/10/2005, together with a complementary search of the Cochrane Central Register of Controlled Trials and MEDLINE, using the keywords antidepressant and panic. A reference search, SciSearch and personal contact with experts were carried out.
SELECTION CRITERIA: Two independent review authors identified randomised controlled trials comparing the combined therapy against either of the monotherapies among adult patients with panic disorder with or without agoraphobia.
DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data using predefined data formats, including study quality indicators. The primary outcome was relative risk (RR) of "response" i.e. substantial overall improvement from baseline as defined by the original investigators. Secondary outcomes included standardised weighted mean differences in global severity, panic attack frequency, phobic avoidance, general anxiety, depression and social functioning and relative risks of overall dropouts and dropouts due to side effects.
MAIN RESULTS: We identified 23 randomised comparisons (representing 21 trials, 1709 patients), 21 of which involved behaviour or cognitive-behaviour therapies. In the acute phase treatment, the combined therapy was superior to antidepressant pharmacotherapy (RR 1.24, 95% confidence interval (CI) 1.02 to 1.52) or psychotherapy (RR 1.17, 95% CI 1.05 to 1.31). The combined therapy produced more dropouts due to side effects than psychotherapy (number needed to harm (NNH) around 26). After the acute phase treatment, as long as the drug was continued, the superiority of the combination over either monotherapy appeared to persist. After termination of the acute phase and continuation treatment, the combined therapy was more effective than pharmacotherapy alone (RR 1.61, 95% CI 1.23 to 2.11) and was as effective as psychotherapy (RR 0.96, 95% CI 0.79 to 1.16).
AUTHORS' CONCLUSIONS: Either combined therapy or psychotherapy alone may be chosen as first line treatment for panic disorder with or without agoraphobia, depending on patient preference.

PMID 17253502  Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004364. d・・・
著者: R Mayou, D Sprigings, J Birkhead, J Price
雑誌名: Psychol Med. 2002 May;32(4):699-706. doi: 10.1017/s0033291702005536.
Abstract/Text BACKGROUND: We sought to determine whether a brief psycho-educational intervention reduced disability in patients with benign palpitation.
METHOD: In a pragmatic randomized controlled trial within a cardiology clinic at a district general hospital, 80 consecutive patients diagnosed as having benign palpitation--either palpitation due to awareness of extrasystoles or sinus rhythm--with associated distress or disability were randomized to an intervention group (usual care plus nurse-delivered intervention based on cognitive-behavioural principles) or to a control group (usual care). Principal outcome was difference in proportion of participants with good or excellent researcher-rated activity levels at 3 months. Subsidiary outcomes were self-rated symptoms, distress and disability, researcher-rated unmet treatment needs.
RESULTS: The principal outcome showed a statistically and clinically significant benefit for the intervention group, with a number needed to treat of 3 (95% CIs 2 to 7). All but one subsidiary outcomes also showed a difference in favour of the intervention group, and several differences reached statistical significance. Significantly more of the control group had unmet treatment needs at 3 months.
CONCLUSIONS: A brief, nurse-delivered, psycho-educational intervention, was an effective treatment for benign palpitation. Further evaluation, including assessment of cost-effectiveness, is needed. The findings have application to the care of patients presenting with other types of 'unexplained' medical symptoms.

PMID 12102384  Psychol Med. 2002 May;32(4):699-706. doi: 10.1017/s0033・・・
著者: Marie-Josée Lessard, André Marchand, Marie-Ève Pelland, Geneviève Belleville, Alain Vadeboncoeur, Jean-Marc Chauny, Julien Poitras, Gilles Dupuis, Richard Fleet, Guillaume Foldes-Busque, Kim L Lavoie
雑誌名: Behav Cogn Psychother. 2012 Mar;40(2):129-47. doi: 10.1017/S1352465811000506. Epub 2011 Sep 20.
Abstract/Text BACKGROUND: Panic disorder (PD) is a common, often unrecognized condition among patients presenting with chest pain to the emergency departments (ED). Nevertheless, psychological treatment is rarely initiated. We are unaware of studies that evaluated the efficacy of brief cognitive-behavioural therapy (CBT) for this population.
AIM: Evaluate the efficacy of two brief CBT interventions in PD patients presenting to the ED with chest pain.
METHOD: Fifty-eight PD patients were assigned to either a 1-session CBT-based panic management intervention (PMI) (n = 24), a 7-session CBT intervention (n = 19), or a usual-care control condition (n = 15). A structured diagnostic interview and self-reported questionnaires were administered at pre-test, post-test, 3- and 6-month follow-ups.
RESULTS: Statistical analysis showed significant reduction in PD severity following both interventions compared to usual care control condition, but with neither showing superiority compared to the other.
CONCLUSIONS: CBT-based interventions as brief as a single session initiated within 2 weeks after an ED visit for chest pain appear to be effective for PD. Given the high prevalence of PD in emergency care settings, greater efforts should be made to implement these interventions in the ED and/or primary care setting.

PMID 21929830  Behav Cogn Psychother. 2012 Mar;40(2):129-47. doi: 10.1・・・
著者: M K Shear, P Houck, C Greeno, S Masters
雑誌名: Am J Psychiatry. 2001 Dec;158(12):1993-8. doi: 10.1176/appi.ajp.158.12.1993.
Abstract/Text OBJECTIVE: Recent studies have suggested that most patients treated for panic disorder receive forms of psychotherapy other than cognitive behavior therapy, even though there is little information about the efficacy of such treatments or how they compare to proven active treatments. The authors compared one of these other forms, emotion-focused psychotherapy (given to 30 patients with panic disorder), to results obtained with recommended standard treatment (either cognitive behavior therapy [N=36] or imipramine [N=22]). The authors also compared emotion-focused psychotherapy to results obtained in subjects given pill placebo (N=24).
METHOD: Subjects met DSM-IV criteria for panic disorder with no more than mild agoraphobia. Treatment consisted of approximately 3 months of weekly visits followed by 6 monthly maintenance visits. Assessments were conducted after each treatment phase and at a follow-up visit after 6 months of no treatment.
RESULTS: Emotion-focused psychotherapy was less effective for symptoms of panic disorder than treatment with either cognitive behavior therapy or imipramine; results obtained with emotion-focused psychotherapy after the acute and maintenance phases were similar to those seen with placebo. Treatment expectations were not different among the different groups. Patients receiving emotion-focused psychotherapy had the highest completion rate.
CONCLUSIONS: The results suggest that emotion-focused psychotherapy (a supportive form of psychotherapy) has low efficacy for the treatment of panic disorder. However, emotion-focused psychotherapy may be superior to medical management in helping patients stay in treatment.

PMID 11729015  Am J Psychiatry. 2001 Dec;158(12):1993-8. doi: 10.1176/・・・
著者: Peter Roy-Byrne, Michelle G Craske, Greer Sullivan, Raphael D Rose, Mark J Edlund, Ariel J Lang, Alexander Bystritsky, Stacy Shaw Welch, Denise A Chavira, Daniela Golinelli, Laura Campbell-Sills, Cathy D Sherbourne, Murray B Stein
雑誌名: JAMA. 2010 May 19;303(19):1921-8. doi: 10.1001/jama.2010.608.
Abstract/Text CONTEXT: Improving the quality of mental health care requires moving clinical interventions from controlled research settings into real-world practice settings. Although such advances have been made for depression, little work has been performed for anxiety disorders.
OBJECTIVE: To determine whether a flexible treatment-delivery model for multiple primary care anxiety disorders (panic, generalized anxiety, social anxiety, and posttraumatic stress disorders) would be better than usual care (UC).
DESIGN, SETTING, AND PATIENTS: A randomized controlled effectiveness trial of Coordinated Anxiety Learning and Management (CALM) compared with UC in 17 primary care clinics in 4 US cities. Between June 2006 and April 2008, 1004 patients with anxiety disorders (with or without major depression), aged 18 to 75 years, English- or Spanish-speaking, were enrolled and subsequently received treatment for 3 to 12 months. Blinded follow-up assessments at 6, 12, and 18 months after baseline were completed in October 2009.
INTERVENTION: CALM allowed choice of cognitive behavioral therapy (CBT), medication, or both; included real-time Web-based outcomes monitoring to optimize treatment decisions; and a computer-assisted program to optimize delivery of CBT by nonexpert care managers who also assisted primary care clinicians in promoting adherence and optimizing medications.
MAIN OUTCOME MEASURES: Twelve-item Brief Symptom Inventory (BSI-12) anxiety and somatic symptoms score. Secondary outcomes included proportion of responders (> or = 50% reduction from pretreatment BSI-12 score) and remitters (total BSI-12 score < 6).
RESULTS: A significantly greater improvement for CALM vs UC in global anxiety symptoms was found (BSI-12 group mean differences of -2.49 [95% confidence interval {CI}, -3.59 to -1.40], -2.63 [95% CI, -3.73 to -1.54], and -1.63 [95% CI, -2.73 to -0.53] at 6, 12, and 18 months, respectively). At 12 months, response and remission rates (CALM vs UC) were 63.66% (95% CI, 58.95%-68.37%) vs 44.68% (95% CI, 39.76%-49.59%), and 51.49% (95% CI, 46.60%-56.38%) vs 33.28% (95% CI, 28.62%-37.93%), with a number needed to treat of 5.27 (95% CI, 4.18-7.13) for response and 5.50 (95% CI, 4.32-7.55) for remission.
CONCLUSION: For patients with anxiety disorders treated in primary care clinics, CALM compared with UC resulted in greater improvement in anxiety symptoms, depression symptoms, functional disability, and quality of care during 18 months of follow-up.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00347269.

PMID 20483968  JAMA. 2010 May 19;303(19):1921-8. doi: 10.1001/jama.201・・・
著者: Nastassja Koen, Dan J Stein
雑誌名: Dialogues Clin Neurosci. 2011;13(4):423-37.
Abstract/Text Given the enormous contribution of anxiety disorders to the burden of disease, it is key to optimize their prevention and treatment. In this critical review we assess advances in the pharmacotherapy of anxiety disorders, as well as remaining challenges, in recent decades, the field has seen rigorous clinical trial methods to quantify the efficacy and safety of serendipitously discovered agents, more focused development of medications with selective mechanisms of action, and the gradual translation of insights from laboratory research into proof-of-principle clinical trials. On the positive side, a considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents. Significant challenges in the field include barriers to appropriate diagnosis and treatment of anxiety disorders, failure of a significant proportion of patients to respond to first-line pharmacotherapy agents, and a limited database of efficacy or effectiveness studies to guide treatment in such cases.

PMID 22275848  Dialogues Clin Neurosci. 2011;13(4):423-37.
著者: M W Otto, K S Tuby, R A Gould, R Y McLean, M H Pollack
雑誌名: Am J Psychiatry. 2001 Dec;158(12):1989-92. doi: 10.1176/appi.ajp.158.12.1989.
Abstract/Text OBJECTIVE: Serotonin selective reuptake inhibitors (SSRIs) are now considered the first-line pharmacotherapy for panic disorder. The preferential use and the presumption of greater tolerability of SSRIs relative to older agents, such as tricyclic antidepressants, occurred without direct comparisons between the two classes of medication. In this study the authors used an effect-size analysis to provide an initial comparison.
METHOD: The authors conducted an effect-size analysis of 12 placebo-controlled, efficacy trials of SSRIs for panic disorder and compared these results to findings obtained in a recent meta-analysis of non-SSRI treatments for panic disorder.
RESULTS: The mean effect size for acute treatment outcome for SSRIs relative to placebo was 0.55, not significantly different from that for antidepressants in general (0.55) and for imipramine in particular (0.48). More recent studies of SSRIs, and studies using larger samples, were associated with lower effect sizes. No significant differences were found in dropout rates between those taking SSRIs and those taking older agents during acute treatment.
CONCLUSIONS: An effect-size analysis of controlled studies of treatments for panic disorder revealed no significant differences between SSRIs and older antidepressants in terms of efficacy or tolerability in short-term trials. An inverse relationship was evident between sample size and effect size for SSRIs. Early studies of small samples may have led to initial overestimations of the efficacy of SSRIs for panic disorder.

PMID 11729014  Am J Psychiatry. 2001 Dec;158(12):1989-92. doi: 10.1176・・・
著者: A Bakker, A J L M van Balkom, P Spinhoven
雑誌名: Acta Psychiatr Scand. 2002 Sep;106(3):163-7. doi: 10.1034/j.1600-0447.2002.02255.x.
Abstract/Text OBJECTIVE: To compare the short-term efficacy of selective serotonin reuptake inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic disorder (PD) a meta-analysis was conducted.
METHOD: Included were 43 studies (34 randomized, nine open), pertaining to 53 treatment conditions, 2367 patients at pretest and 1804 at post-test. Outcome was measured with the proportion of patients becoming panic-free, and with pre/post Cohen's d effect sizes, calculated for four clinical variables: panic, agoraphobia, depression, and general anxiety.
RESULTS: There were no differences between SSRIs and TCAs on any of the effect sizes, indicating that both groups of antidepressants are equally effective in reducing panic symptoms, agoraphobic avoidance, depressive symptomatology and general anxiety. Also the percentage of patients free of panic attacks at post-test did not differ. The number of drop-outs, however, was significantly lower in the group of patients treated with SSRIs (18%) vs. TCAs (31%).
CONCLUSION: SSRIs and TCAs are equal in efficacy in the treatment of panic disorder, but SSRIs are tolerated better.

Copyright Blackwell Munksgaard 2002.
PMID 12197851  Acta Psychiatr Scand. 2002 Sep;106(3):163-7. doi: 10.10・・・
著者: W Boyer
雑誌名: Int Clin Psychopharmacol. 1995 Mar;10(1):45-9. doi: 10.1097/00004850-199503000-00006.
Abstract/Text The etiology and optimum treatment of panic disorder remain unclear. Imipramine and alprazolam are reasonably well established treatments. Several reports have suggested that serotonin reuptake inhibitors may also be effective for this condition. To investigate this issue, 27 published or presented placebo-controlled, double-blind studies of DSM-III or DSM-III-R panic disorder were subjected to meta-analysis. The serotonin reuptake inhibitors included paroxetine, fluvoxamine, zimelidine, and clomipramine. The standard treatments were imipramine or alprazolam. All three treatments were highly significantly superior to placebo in alleviating panic. The serotonin reuptake inhibitors were also significantly superior to both imipramine and alprazolam. The superiority of the serotonin reuptake inhibitors remained, but was less pronounced, when they were compared to the studies which used higher doses of imipramine or alprazolam. These findings underscore the importance of serotonin reuptake inhibitors in the treatment of panic disorder and indirectly add to the evidence that serotonergic abnormalities may have a role in its etiology.

PMID 7622804  Int Clin Psychopharmacol. 1995 Mar;10(1):45-9. doi: 10.・・・
著者: M H Pollack, M H Rapaport, C M Clary, J Mardekian, R Wolkow
雑誌名: J Clin Psychiatry. 2000 Dec;61(12):922-7.
Abstract/Text BACKGROUND: More than one third of panic disorder patients have a chronic and/or recurrent form of the disorder, accounting for much of the individual and societal cost associated with the illness. Six clinical variables have been most consistently identified as high-risk predictors of poor outcome: (1) panic severity, (2) presence of agoraphobia, (3) comorbid depression, (4) comorbid personality disorder, (5) duration of illness, and (6) female sex. No published research has systematically examined the differential antipanic efficacy of selective serotonin reuptake inhibitors in patients at high risk for poor outcome.
METHOD: Data were pooled (N = 664) from 4 double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of DSM-III-R panic disorder. Two of the studies were 12-week fixed-dose studies with starting daily doses of sertraline, 50 mg, and 2 were 10-week flexible-dose studies with starting daily doses of sertraline, 25 mg. All other study design features were the same, except for the exclusion of women of childbearing potential in the 2 fixed-dose studies. Exclusion of patients with marked personality disorders and depression meant that only 4 of the poor-outcome variables could be evaluated.
RESULTS: Clinical improvement was similar for patients treated with sertraline whether or not they carried an agoraphobia diagnosis, had a duration of illness > 2 years, or were female. Patients with high baseline panic severity had significantly (p = .01) less improvement on the endpoint Clinical Global Impressions-Improvement (CGI-I) scale than patients with moderate severity, although the Clinical Global Impressions-Severity of Illness scale change score was higher in the patients with high severity (-2.00 vs. -1.31). For patients with 3 or more high-risk variables, there was a modest, but statistically significant, tendency for reduced global improvement (endpoint CGI-I score of 2.7 for the high-risk vs. 2.4 for the non-high-risk group; p = .017), although the high-risk group actually had a similar endpoint reduction in frequency of panic attacks (82%) compared with the non-high-risk group (78%).
CONCLUSION: Treatment of panic disorder with sertraline was generally effective, even in the presence of baseline clinical variables that have been associated with poor treatment response. The main limitations of the analysis were the reliance on pooled data from 4 studies (even if the designs were similar) and our inability to examine the impact of depression and personality disorders on response to treatment because of the exclusion criteria of the clinical trials.

PMID 11206597  J Clin Psychiatry. 2000 Dec;61(12):922-7.
著者: Alessandro Serretti, Alberto Chiesa, Raffaella Calati, Giampaolo Perna, Laura Bellodi, Diana De Ronchi
雑誌名: Neuropsychobiology. 2011;63(1):1-7. doi: 10.1159/000321831. Epub 2010 Oct 20.
Abstract/Text AIM: The aim of the present review is to summarize available evidence about the efficacy and side effects of novel antidepressants for the treatment of panic disorder.
METHODS: A literature search was undertaken using MEDLINE, ISI web of knowledge and references of retrieved articles. The search included articles published in English up to September 2009. Both controlled and uncontrolled trials were included. The quality of the reviewed articles was also assessed.
RESULTS: Fourteen mainly poor-quality studies were included. Mirtazapine showed some efficacy in reducing the number and the severity of panic symptoms in many uncontrolled studies and was comparable to selective serotonin reputake inhibitors (SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious than placebo but less effective than SSRIs. Further uncontrolled studies suggested preliminary evidence for the use of milnacipran and duloxetine as well. All drugs were usually well tolerated.
DISCUSSION: Current studies do not yet provide convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran and duloxetine for the treatment of panic disorder patients. However, on account of positive preliminary results, further research is warranted.

Copyright © 2010 S. Karger AG, Basel.
PMID 20962541  Neuropsychobiology. 2011;63(1):1-7. doi: 10.1159/000321・・・
著者: R Noyes, M J Garvey, B L Cook, L Samuelson
雑誌名: J Clin Psychiatry. 1989 May;50(5):163-9.
Abstract/Text The authors followed up 107 patients with panic disorder or agoraphobia with panic attacks who had been placed on a regimen of tricyclic antidepressant treatment 1 to 4 years earlier. Sixty-three percent reported at least moderate improvement during treatment; however, side effects were often difficult to tolerate, and 35% discontinued tricyclic treatment on this account. Overstimulation, which occurred in 20%, was the most frequent reason for early termination, and weight gain, which occurred in 34%, was the most common reason for stopping the drug later on. Seizures occurred in 2 patients. Even though they were encouraged to discontinue drug use, most of the patients who had responded were still taking their drugs at follow-up. More than half of those who had responded before stopping drug treatment subsequently relapsed. The findings highlight problems with safety, side effects, and patient acceptance resulting from the use of tricyclic antidepressants in patients with anxiety disorders.

PMID 2715139  J Clin Psychiatry. 1989 May;50(5):163-9.
著者: R Pohl, V K Yeragani, R Balon, H Lycaki
雑誌名: J Clin Psychiatry. 1988 Mar;49(3):100-4.
Abstract/Text The jitteriness syndrome (jitteriness, shakiness, increased anxiety, and insomnia) can develop with low doses of tricyclic antidepressants in patients who are sensitive to these drugs. The authors review the antidepressant treatment of 180 patients. Only those with panic attacks had jitteriness, usually during the first week of treatment. Desipramine was associated with a much higher frequency of jitteriness than was imipramine. Tolerance to jitteriness occurred with continued treatment, but fewer patients with jitteriness responded to treatment, apparently because of difficulties in increasing the dose. Characteristics of the jitteriness syndrome in panic disorder patients are consistent with noradrenergic hypotheses of panic anxiety. The clinical and theoretical implications of these findings are discussed.

PMID 3346196  J Clin Psychiatry. 1988 Mar;49(3):100-4.
著者: Lindsey I Sinclair, David M Christmas, Sean D Hood, John P Potokar, Andrea Robertson, Andrew Isaac, Shrikant Srivastava, David J Nutt, Simon J C Davies
雑誌名: Br J Psychiatry. 2009 Jun;194(6):483-90. doi: 10.1192/bjp.bp.107.048371.
Abstract/Text BACKGROUND: Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking.
AIMS: To review systematically all evidence relating to jitteriness/anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions.
METHOD: A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.
RESULTS: Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome.
CONCLUSIONS: Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

PMID 19478285  Br J Psychiatry. 2009 Jun;194(6):483-90. doi: 10.1192/b・・・
著者: C L Ravaris, M J Friedman, P J Hauri, G J McHugo
雑誌名: J Clin Psychopharmacol. 1991 Dec;11(6):344-50.
Abstract/Text We studied the efficacy of propranolol (Inderal) compared to alprazolam (Xanax) in 29 patients with a diagnosis of agoraphobia with panic disorder or panic disorder with or without limited phobic avoidance in a 6-week double-blind controlled experiment. Alprazolam is effective in those syndromes, whereas to date only negative or ambiguous results had been reported for propranolol. Fourteen patients received a mean daily dose of 5.0 +/- 2.3 mg of alprazolam and 15 patients received 182.0 +/- 60.5 mg mean daily dose of propranolol. We found both drugs to be effective to suppress panic attacks and reduce avoidance behavior. The only significant between-drug difference was a more rapid onset of alprazolam's panicolytic effect. Propranolol merits further study. We suggest patients worthy of a clinical trial.

PMID 1770152  J Clin Psychopharmacol. 1991 Dec;11(6):344-50.
著者: S Hirschmann, P N Dannon, I Iancu, O T Dolberg, J Zohar, L Grunhaus
雑誌名: J Clin Psychopharmacol. 2000 Oct;20(5):556-9. doi: 10.1097/00004714-200010000-00011.
Abstract/Text The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder (PD). Twenty-five outpatients having PD with or without agoraphobia were included. These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day. Treatment-resistant PD was defined as a less than 20% reduction in score on the Panic Self-Questionnaire (number of attacks per week) (PSQ) and the Clinical Anxiety Scale With Panic Attacks (CAS+PA). These patients continued to receive fluoxetine 20 mg/day and were randomly assigned to additionally receive either pindolol (2.5 mg three times daily) or placebo for the following 4 weeks. Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression (HAM-D), the CAS+PA, the NIMH Anxiety Scale, the PSQ, and the Clinical Global Impression Scale. The data were analyzed using a repeated-measures analysis of variance (ANOVA) and a t-test for independent samples. Patients treated with the combination of pindolol and fluoxetine (N = 13) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales, with the exception of HAM-D. The statistical differences were shown using the repeated-measures ANOVA (baseline, week 2, week 4) and also with t-tests from the second week of the trial. These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD.

PMID 11001241  J Clin Psychopharmacol. 2000 Oct;20(5):556-9. doi: 10.1・・・
著者: P Blier, R Bergeron
雑誌名: J Clin Psychiatry. 1998;59 Suppl 5:16-23; discussion 24-5.
Abstract/Text Serotonin (5-HT) selective reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors are thought to have a delayed onset of antidepressant action attributable in part to the decrease in firing activity of 5-HT neurons they produce upon treatment initiation. As cell body 5-HT1A autoreceptors desensitize, 5-HT neuronal firing is restored. The agent pindolol, through its 5-HT1A receptor blocking property, has been shown to prevent the initial decrease in firing of rat 5-HT neurons associated with SSRI treatment. Four open-label studies put into evidence a significant acceleration of the antidepressant effect of SSRIs when combined with pindolol. Four of five placebo-controlled studies have confirmed this observation. Controlled trials indicate that a greater rate of response may be obtained by combining pindolol from the beginning of the SSRI treatment. The strategy of adding pindolol to the regimen of SSRI-resistant patients also appears to produce a therapeutic effect in a significant proportion of patients.

PMID 9635544  J Clin Psychiatry. 1998;59 Suppl 5:16-23; discussion 24・・・
著者: T Hamada, Y Koshino, T Misawa, K Isaki, F Gejyo
雑誌名: Acta Psychiatr Scand. 1998 Feb;97(2):139-43. doi: 10.1111/j.1600-0447.1998.tb09976.x.
Abstract/Text We investigated the significance of mitral valve prolapse (MVP) and autonomic function in 121 patients diagnosed with panic disorder (PD). The incidence of MVP was higher in these patients (32.2%) than in the healthy controls (16.7%), but the difference was not significant. In the group with PD accompanied by depression, the MVP rate was 58.1%, significantly higher than the value of 25.7% observed in the PD patients without depression. The severity of MVP was mild; nearly all of the cases were silent, without cardiac murmur, and there was no problem with the left ventricular function. The coefficient of variation for R-R intervals on electrocardiograms (CV R-R) was smaller in patients with PD than in healthy controls. The CV R-R of PD patients was significantly lower in the group with MVP than in the group without MVP, suggesting a strong association with the parasympathetic nervous system. Since the CV R-R tended to decrease in the presence of depression, involvement of the parasympathetic nervous system was inferred.

PMID 9517908  Acta Psychiatr Scand. 1998 Feb;97(2):139-43. doi: 10.11・・・
著者: G Wilkinson, M Balestrieri, M Ruggeri, C Bellantuono
雑誌名: Psychol Med. 1991 Nov;21(4):991-8. doi: 10.1017/s0033291700029986.
Abstract/Text Meta-analysis of 19 double-blind placebo-controlled trials of antidepressants (N = 13) and benzodiazepines (N = 6) for patients with panic disorders showed that active treatment had 25% greater success rate than placebo over a mean duration of 14 weeks. There were no statistically significant differences observed between treatment sub-groups (antidepressants--mean duration 16 weeks; and benzodiazepines--mean duration 7 weeks). On this basis antidepressants and benzodiazepines prescribed in clinical settings are likely to be equally effective in the short-term treatment of people with panic disorders.

PMID 1685792  Psychol Med. 1991 Nov;21(4):991-8. doi: 10.1017/s003329・・・
著者: I M Marks, R P Swinson, M Başoğlu, K Kuch, H Noshirvani, G O'Sullivan, P T Lelliott, M Kirby, G McNamee, S Sengun
雑誌名: Br J Psychiatry. 1993 Jun;162:776-87. doi: 10.1192/bjp.162.6.776.
Abstract/Text A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.

PMID 8101126  Br J Psychiatry. 1993 Jun;162:776-87. doi: 10.1192/bjp.・・・
著者: J Wardle, P Hayward, A Higgitt, M Stabl, R Blizard, J Gray
雑誌名: Behav Res Ther. 1994 Feb;32(2):203-15. doi: 10.1016/0005-7967(94)90113-9.
Abstract/Text In a study designed to evaluate the impact of benzodiazepine use on the outcome of behaviour therapy, 91, severe, chronic agoraphobics (46 BDZ users and 45 non-users) were randomly allocated on a double-blind basis to in vivo exposure with low-dose diazepam (ED) or placebo (EP). Drug doses were adjusted on the basis of weekly psychiatric assessments over weeks 1-4. Patients had 8 x 2 hr exposure sessions (weeks 5-12) and were then withdrawn from medication (weeks 13-16). Re-assessments were completed at weeks 4, 12 and 16, and follow-up assessments at approx 20, 46 and 72 weeks. In the analysis of the results, the clinical outcome was evaluated in relation to the therapeutic regime (ED vs EP) and prior BDZ use (users vs non-users). The results showed that the ED group had greater changes in anxiety than the EP group during the drug manipulation phases (anxiety increasing during BDZ withdrawal). There were no group differences in agoraphobic symptoms and no evidence that the outcome of the behavior therapy was significantly affected by concurrent BDZ treatment. There were significant improvements in agoraphobic symptoms over the treatment period, with no evidence for relapse of treatment gains on withdrawal from BDZ, nor for differential responses over the one year follow-up. Initial differences between users and non-users were less marked than expected, although there was a trend for more drop-outs among users across both ED and EP groups.

PMID 7908800  Behav Res Ther. 1994 Feb;32(2):203-15. doi: 10.1016/000・・・
著者: Carlos Israel Pérez Benítez, Kevin Smith, Russell G Vasile, Richard Rende, Maria Orlando Edelen, Martin B Keller
雑誌名: Am J Geriatr Psychiatry. 2008 Jan;16(1):5-13. doi: 10.1097/JGP.0b013e31815aff5c.
Abstract/Text OBJECTIVE: The purpose of this study was to examine the use of benzodiazepines (BZs) and selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors (SSRIs/SNRIs) over nine years of follow-up in middle-aged and older adults with diagnoses of panic disorder with or without agoraphobia, social phobia, or generalized anxiety disorder.
SETTING AND PARTICIPANTS: Participants in this study were enrolled in the Harvard/Brown Anxiety Research Project (HARP). HARP is a naturalistic, longitudinal, multisite study of adults with anxiety disorders who are recruited from psychiatric settings. The analytic sample consisted of 51 participants with anxiety disorders who were 55 to 70 years old at baseline and a younger cohort of 211 participants added for comparative analysis.
DESIGN: The authors examined patterns of medication use (BZs and SSRIs/SNRIs) in participants with anxiety disorders as they aged, by assessing the proportion of participants taking these medications using generalized estimating equation modeling.
MEASUREMENTS: The present data were derived from the structured diagnostic interview administered at enrollment using a combination of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Third Edition-R Non-Affective Disorder, Patient Version, Research Diagnostic Criteria Schedule for Affective Disorders-Lifetime, and subsequent follow-up interviews over a nine-year period using the Longitudinal Interval Follow-up Evaluation-Pharmacia & Upjohn to assess the weekly course of disorders to indicate syndrome severity and document medication use by specific type and dose on a weekly basis.
RESULTS: Findings showed that rates of BZ use were high among both the older (53% at baseline) and the younger (57.4%) age groups and did not significantly decrease over time, after controlling for time in episode of their anxiety disorders. There was a statistically significant increase in SSRI/SNRI use over time in both groups. At the beginning of the study, 18% of the older group and 21% of the younger group were using SSRIs/SNRIs; however, at the end of the study, the rates increased to 35% and 43%, respectively.
CONCLUSIONS: Although there was an increase in SSRI/SNRI use in older participants with anxiety disorders over the course of study, at nine years of follow-up, only 35% of participants were utilizing SSRI/SNRI medication, while more than one-half of the same participants were continuing to use BZs. To the authors' knowledge, there are no randomized clinical trials that have addressed comparative efficacy and safety of BZs and SSRIs/SNRIs in this population. However, there is documented evidence of adverse effects of chronic BZ use and the risk of developing dependency in older populations.

PMID 18165458  Am J Geriatr Psychiatry. 2008 Jan;16(1):5-13. doi: 10.1・・・

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