今日の臨床サポート

パニック障害

著者: 塩入俊樹 岐阜大学大学院医学系研究科神経統御学講座

監修: 上島国利 昭和大学

著者校正済:2021/11/24
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. パニック障害の慢性、反復性で残存症状を認めやすいという特徴からは、当然、長期薬物療法は効果的であり、必要なはずである(推奨度2)。
  1. 医師はパニック障害の治療によって症状が消失し、治療終了の時期を考えるようになったときに、あらためてその治療自体のメリット・デメリットを総合的に判断し、治療継続期間についての決定を患者とともに行わなければならない(推奨度1)。
  1. 薬物療法による寛解率は20~50%、治療終了後の再発率は25~85%との報告がある。したがって、パニック障害の治療をどこまで続けるかの判断を問われたとき、再発に関連した因子を探ることが推奨される(推奨度2)。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
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:
塩入俊樹 : 特に申告事項無し[2021年]
監修:上島国利 : 原稿料(大日本住友製薬)[2021年]

改訂のポイント:
  1. 定期レビューを行い、推奨度の見直し、エビデンスランクについての加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. パニック障害とは、突然生じる動悸や発汗、呼吸困難感などの自律神経症状と強い恐怖感を伴う不安発作(=パニック発作)などを主徴とする精神疾患である。
  1. 疾患の頻度は高く、2005年の米国調査によると、生涯有病率は4.7%、わが国における05年の調査においても、12カ月の有病率は0.5%とされている。
  1. パニック障害は、パニック発作を抑え、回避行動を改善させることで、発症時に生じていた著しい社会機能障害を改善させることができるとの結果があるため、診断し、治療を開始することが勧められる。
病歴・診察のポイント  
  1. 大うつ病性障害(うつ病)や双極性障害(躁うつ病)などの気分障害や、社交不安障害、特定の恐怖症などの不安障害、さらに薬物依存症などの併発・併存の有無を確認する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者:
雑誌名: Am J Psychiatry. 1998 May;155(5 Suppl):1-34.
Abstract/Text
PMID 9585731  Am J Psychiatry. 1998 May;155(5 Suppl):1-34.
著者: Alicia C Doyle, Mark H Pollack
雑誌名: J Clin Psychiatry. 2003;64 Suppl 15:40-5.
Abstract/Text Anxiety disorders such as generalized anxiety disorder, social anxiety disorder, panic disorder, and posttraumatic stress disorder are typically chronic conditions associated with high health care costs and are often accompanied by psychiatric comorbidity, including major depressive disorder, substance abuse, and other anxiety disorders. Anxiety disorders are associated with significant functional impairment in social, vocational, and familial spheres and with diminished overall quality of life. The following clinical overview provides informal guidelines for identifying remission in patients with an anxiety disorder. A systematic approach to treatment that includes patient education, encouragement of exposure, attention to relevant comorbidities, use of empirically proven pharmacotherapies, and psychosocial interventions of adequate intensity and duration will improve outcomes and move patients toward marked improvement and remission.

PMID 14658990  J Clin Psychiatry. 2003;64 Suppl 15:40-5.
著者: G A Fava, L Mangelli
雑誌名: Psychother Psychosom. 1999;68(6):281-9. doi: 12345.
Abstract/Text The aim of this review was to survey the available literature on prodromal and residual symptoms of panic disorder. Both a computerized (Medline) and a manual search of the literature were performed. In a substantial proportion of patients with panic disorder with agoraphobia a prodromal phase can be identified. Most patients report residual symptoms despite successful treatment. Residual symptoms upon remission have a prognostic value. There appears to be a relationship between residual and prodromal symptomatology (the rollback phenomenon). Appraisal of subclinical symptomatology in panic disorder has important implications as to the pathophysiological model of disease, its conceptualization and treatment.

Copyright 1999 S.Karger AG,Basel.
PMID 10559707  Psychother Psychosom. 1999;68(6):281-9. doi: 12345.
著者: G Gardos
雑誌名: J Psychiatr Pract. 2000 May;6(3):140-6.
Abstract/Text The author followed 67 patients with panic disorder with agoraphobia (PDA) for a minimum of 5 years in a private practice setting. They were treated with a combination of pharmacotherapy (antidepressants or benzodiazepines) and cognitive-behavioral psychotherapy. The author examines outcomes for three groups: A) 11 male patients, 10 of whom had comorbid conditions; B) 21 female patients with comorbid conditions; and C) 35 female patients without comorbid conditions. Symptom severity was assessed using the Panic Disorder Severity Scale (PDSS). Patients in all groups showed marked improvement in all the domains measured by the PDSS, with the greatest improvement in PDSS scores occurring during the first year in all three groups. Patients in groups A and B tended to plateau after 5 years of treatment and show no additional improvement thereafter, whereas patients in group C (women with "pure PDA") continued to improve, although at a gradually slower rate. However, after an average of 11 years of treatment, the majority of patients remained symptomatic. The presence of comorbid alcohol abuse or depression was associated with poorer outcomes. The results in this effectiveness study are generally not as good as the outcomes of published PDA follow-up efficacy studies, but appear to be superior to outcomes in cohorts of chronically anxious patients treated decades ago.

PMID 15990481  J Psychiatr Pract. 2000 May;6(3):140-6.
著者: W Katon, P P Vitaliano, K Anderson, M Jones, J Russo
雑誌名: Compr Psychiatry. 1987 Mar-Apr;28(2):151-8.
Abstract/Text
PMID 3829658  Compr Psychiatry. 1987 Mar-Apr;28(2):151-8.
著者: H Katschnig, M Amering, J M Stolk, J C Ballenger
雑誌名: Psychopharmacol Bull. 1996;32(1):149-55.
Abstract/Text In a prospective 4 year followup study, 423 panic disorder patients participated in one of two international multicenter drug trials. They were to be reinterviewed 4 years after leaving the trials; 367 (86.8%) interviews were completed. At followup, 3 of 5 patients still suffered from at least occasional panic attacks, and 2 of 5 were still agoraphobic, but only about 20 percent of the patients were still disabled. The only baseline variables that predicted disabilities at followup were the disability measures at baseline themselves. Neither panic attack frequency nor phobic avoidance at baseline predicted disability at followup. Because of the lack of association between the presence of symptoms and of social disabilities, future clinical trials and other clinical and epidemiological studies should use independent symptom measures and quality-of-life measures simultaneously.

PMID 8927665  Psychopharmacol Bull. 1996;32(1):149-55.
著者: H Katschnig, M Amering
雑誌名: J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):6S-11S.
Abstract/Text Whereas lifetime prevalence rates of panic disorder--as established in epidemiologic surveys--range between 1.6 and 3.5%, 1-month rates usually amount to much less than one half of the lifetime rates. This finding indicates that a substantial proportion of patients who had panic disorder at some stage in their life must have remitted. In contrast to these results, clinicians tend to regard panic disorder as a chronic condition because, as a rule, they see panic patients only several years after onset of the disorder. A number of small, prospective, long-term studies of such clinical populations indicate that after several years, between 17 and 70% of patients still have panic attacks, and between 36 and 82% have phobic avoidance. In the largest and longest follow-up study published to date, 45% of all patients showed an unremitting--although in a certain proportion waxing and waning--course, 24% followed a pattern of remissions and relapses, whereas 31% went back into a stable remission. The evidence of factors predicting the course of panic disorder in clinical populations suggests that long duration and agoraphobia at baseline--not the severity and frequency of panic attacks--are predictors of an unfavorable course. Additional studies are needed to determine whether personality factors, depression, and other variables are also of predictive relevance. Also, factors working during follow-up, such as positive and negative life events, coping behaviors, and treatment, should be considered in future studies.

PMID 9872707  J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):6S-11S.
著者: Carlo Marchesi, Alessandro Cantoni, Stefania Fontò, Maria R Giannelli, Carlo Maggini
雑誌名: J Affect Disord. 2005 Dec;89(1-3):189-94. doi: 10.1016/j.jad.2005.07.007. Epub 2005 Oct 4.
Abstract/Text BACKGROUND: In this prospective study, Personality Disorders (PersD) were evaluated in patients with Panic Disorder (PD), before and after one year of pharmacotherapy to verify whether personality characteristics changed after treatment.
METHOD: Sixty PD patients and 60 sex and age-matched normal controls participated in the study. All subjects were evaluated with the SCID-IV, the Structured Interview for DSM-IV Personality Disorders (SIDP), the SCL-90, the Ham-A and the Ham-D. Patients were treated with paroxetine or citalopram and were evaluated monthly for one year to assess the remission of symptoms. The SIDP was re-administered to the patients at the end of the study.
RESULTS: Before treatment, PD patients showed a higher prevalence (60%) of PersD than normal subjects (8%). After treatment, PersD rate decreased (43%) due to the reduction of the rate of paranoid, avoidant and dependent PersD. When the effect of the treatment on personality traits was evaluated, we found that avoidant traits decreased only in remitted patients, paranoid traits decreased both in remitted and in non-remitted patients, and dependent traits decreased only in patients with major depression comorbidity.
LIMITATIONS: The small sample size and the short length of the follow-up period of our study suggest caution in the generalization of our results.
CONCLUSIONS: In our PD patients, an improvement of symptoms was associated with a reduction of paranoid, avoidant and dependent traits, with a normalization of paranoid traits and a persistence of avoidant and dependent characteristics. Therefore, our data suggest that in PD patients not only paranoid traits but also avoidant and dependent traits show, at least in part, a state phenomenon.

PMID 16209891  J Affect Disord. 2005 Dec;89(1-3):189-94. doi: 10.1016/・・・
著者: Giulio Perugi, Franco Frare, Cristina Toni
雑誌名: CNS Drugs. 2007;21(9):741-64.
Abstract/Text Agoraphobia with panic disorder is a phobic-anxious syndrome where patients avoid situations or places in which they fear being embarrassed, or being unable to escape or get help if a panic attack occurs. During the last half-century, agoraphobia has been thought of as being closely linked to the recurring panic attack syndrome, so much so that in most cases it appears to be the typical development or complication of panic disorder. Despite the high prevalence of agoraphobia with panic disorder in patients in primary-care settings, the condition is frequently under-recognised and under-treated by medical providers. Antidepressants have been demonstrated to be effective in preventing panic attacks, and in improving anticipatory anxiety and avoidance behaviour. These drugs are also effective in the treatment of the frequently coexisting depressive symptomatology. Among antidepressant agents, SSRIs are generally well tolerated and effective for both anxious and depressive symptomatology, and these compounds should be considered the first choice for short-, medium- and long-term pharmacological treatment of agoraphobia with panic disorder. The few comparative studies conducted to date with various SSRIs reported no significant differences in terms of efficacy; however, the SSRIs that are less liable to produce withdrawal symptoms after abrupt discontinuation should be considered the treatments of first choice for long-term prophylaxis. Venlafaxine is not sufficiently studied in the long-term treatment of panic disorder, while TCAs may be considered as a second choice of treatment when patients do not seem to respond to or tolerate SSRIs. High-potency benzodiazepines have been shown to display a rapid onset of anti-anxiety effect, having beneficial effects during the first few days of treatment, and are therefore useful options for short-term treatment; however, these drugs are not first-choice medications in the medium and long term because of the frequent development of tolerance and dependence phenomena. Cognitive-behavioural therapy is the best studied non-pharmacological approach and can be applied to many patients, depending on its availability.

PMID 17696574  CNS Drugs. 2007;21(9):741-64.
著者: M H Pollack, J W Smoller
雑誌名: Psychiatr Clin North Am. 1995 Dec;18(4):785-801.
Abstract/Text Converging lines of evidence from a variety of methods of inquiry support a developmental model for panic disorder that includes a constitutional predisposition for anxiety influenced by genetic, familial, cognitive-behavioral and psychosocial factors, early expression during childhood, and variable manifestations during the life-cycle. Studies of patients followed up after acute pharmacotherapy trials and those treated naturalistically are consistent with this model and portray panic disorder as a generally chronic condition with a longitudinal course marked by relatively brief intervals of remission and high rates of recurrence and relapse. Longitudinal and follow-up studies suggest that panic attack frequency responds more readily and rapidly to pharmacotherapy than do other aspects of panic disorder such as agoraphobia and generalized anxiety. In general, the presence of agoraphobia is associated with more severe symptoms, greater chronicity, and more limited response to treatment. Other variables associated with chronicity and treatment resistance include patient-related factors (psychiatric and medical comorbidity, anxiety sensitivity) and pharmacologic factors (adequacy of dose, duration, and compliance). Although it is currently difficult to predict the duration of treatment needed for an individual patient, available evidence suggests that a substantial proportion of patients may require chronic treatment for panic disorder.

PMID 8748381  Psychiatr Clin North Am. 1995 Dec;18(4):785-801.
著者: B R Slaap, J A den Boer
雑誌名: Depress Anxiety. 2001;14(2):112-22.
Abstract/Text Several effective pharmacotherapeutic treatments exist for panic disorder; however, not all patients respond to treatment: between 20% to 40% are non-responders. Recent studies have reported several predictors of nonresponse to pharmacotherapy. In this review two questions are addressed: is there consensus with respect to predictors of nonresponse and are there any differences between short-term and long-term predictors? In this review both short-term and long-term outcome studies are discussed. Studies were included if at least DSM-III criteria were used and baseline variables were investigated as possible predictor of response, or nonresponse, to pharmacotherapy. Of each clinical predictor, tallies were made of the particular predictors employed and of those predictors that predicted nonresponse. It appears that a long duration of illness and severe agoraphobic avoidance are robust predictors of nonresponse, particularly in long-term studies. Personality disorders, or even personality traits, are possibly the most robust predictors of nonresponse. Several factors appear to be robust predictors of nonresponse: factors that are present before treatment and exert their influence on short-term and long-term treatment outcome. Prospective studies are needed to further investigate these factors and to test whether it is viable to intervene in an attempt to increase treatment response.

Copyright 2001 Wiley-Liss, Inc.
PMID 11668664  Depress Anxiety. 2001;14(2):112-22.
著者: J C Ballenger, J R Davidson, Y Lecrubier, D J Nutt, D S Baldwin, J A den Boer, S Kasper, M K Shear
雑誌名: J Clin Psychiatry. 1998;59 Suppl 8:47-54.
Abstract/Text OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in panic disorder and guide clinical practice with recommendations for appropriate pharmacotherapy.
PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Four faculty invited by the chairman also participated: David S. Baldwin, Johan A. den Boer, Siegfried Kasper, and M. Katherine Shear.
EVIDENCE: The consensus statement is based on the 6 review papers that are published in this supplement and on the scientific literature relevant to these issues.
CONSENSUS PROCESS: There were group meetings held during a 2-day period. On day 1, the group discussed each review paper and the chairman and discussant (Dr. Kasper) identified key issues for further debate. On day 2, the group discussed these key issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chairman and approved by all attendees.
CONCLUSIONS: The consensus statement provides standard definitions for response and remission and identifies appropriate strategy for the management of panic disorder in a primary care setting. Serotonin selective reuptake inhibitors are recommended as drugs of first choice with a treatment period of 12 to 24 months. Pharmacotherapy should be discontinued slowly over a period of 4 to 6 months.

PMID 9707162  J Clin Psychiatry. 1998;59 Suppl 8:47-54.
著者: J C Ballenger
雑誌名: J Clin Psychiatry. 2001;62 Suppl 12:5-9.
Abstract/Text Treating anxiety disorders to remission should be the goal of all practitioners. A remitted patient should be well, both in symptoms and function, and be indistinguishable from a never-ill counterpart. The definition of remission in patients with anxiety disorders should also be clear, practical, and easy to use. It is useful to measure response in an objective way, such as with standardized instruments appropriate for the disorder, and to develop remission criteria specific to each disorder. This article proposes remission criteria, using standardized measures, for 5 common anxiety disorders: panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder.

PMID 11430617  J Clin Psychiatry. 2001;62 Suppl 12:5-9.
著者: James C Ballenger
雑誌名: J Clin Psychiatry. 2004 Dec;65(12):1696-707.
Abstract/Text BACKGROUND: Approximately 50% to 60% of patients with depression and/or anxiety respond to treatment, but only a minority achieve remission. The continued presence of subsyndromal symptoms in treated depressed (and probably anxious) patients leads to higher relapse rates and increased utilization of health care resources. It is proposed that remission is the appropriate target in the treatment of both depression and the anxiety disorders.
AIMS: Rigorous criteria for remission have been proposed for the anxiety disorders and are currently being applied in clinical studies. Using these criteria, data from the paroxetine clinical study database were retrospectively analyzed to determine remission rates following paroxetine treatment across a range of anxiety disorders in the largest analysis of remission data in the anxiety disorders to date.
METHOD: These analyses included data from 16 short-term and 6 long-term, randomized, placebo-controlled studies in panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder (short term only), and generalized anxiety disorder (DSM-III-R or DSM-IV). Separate analyses were performed for each disorder, with short- and long-term data analyzed separately.
RESULTS: In general, across the range of anxiety disorders studied, in both short- and long-term studies, remission rates were higher for paroxetine compared with placebo, using disorder-specific, global, and functional remission criteria both individually and combined. Remission occurred in a moderate proportion of paroxetine-treated patients after only 8 to 12 weeks of treatment, and longer-term therapy led to even higher remission rates.
CONCLUSION: Paroxetine has demonstrated efficacy in treating patients to remission across the range of anxiety disorders studied. Our findings strongly suggest that continuing treatment with paroxetine (and probably other SSRI antidepressants) for 2 to 12 months increases the proportion of patients achieving clinical remission.

PMID 15641876  J Clin Psychiatry. 2004 Dec;65(12):1696-707.
著者: Borwin Bandelow
雑誌名: CNS Spectr. 2006 Oct;11(10 Suppl 12):21-8.
Abstract/Text Response and remission rates are commonly used to evaluate the efficacy of treatments for anxiety disorders and other psychiatric illnesses. Response is generally regarded as a clinically meaningful improvement in symptoms, while remission, the goal of treatment, is generally thought of as the absence or near absence of symptoms following illness, accompanied by a return to premorbid levels of functioning. Response and remission are often defined using psychiatric rating scales, based on score cutoffs or the magnitude of score changes from baseline. While no universally accepted criteria exist, a commonly used threshold for response is a >50% improvement in the total score, while for remission, various cutoff points have been used. Comparison of cutoffs or change scores for disease-specific scales with Clinical Global Impressions ratings is a useful way of evaluating response and remission criteria across disorders. To illustrate the use of disease-specific and global measures, this article summarizes data from randomized, placebo-controlled studies of adult patients with generalized anxiety disorder, social anxiety disorder, or panic disorder treated with the serotonin norepinephrine reuptake inhibitor venlafaxine extended release, for which acute-phase data are available (a total of 13 trials).

PMID 17008827  CNS Spectr. 2006 Oct;11(10 Suppl 12):21-8.
著者: U Lepola, H Koponen, E Leinonen
雑誌名: Acta Psychiatr Scand. 1996 Mar;93(3):181-3.
Abstract/Text A clinical sample of 55 patients meeting the diagnostic criteria for panic disorder (PD) were enrolled in this long-term study. The patients were treated initially with alprazolam or imipramine during a period of 9 weeks. A clinical psychiatric examination was carried out at the beginning and at the end of the initial treatment period and 3 and 6 years after the enrollment. Although most of the patients (74%) had no panic attacks at the end of the 6-year follow-up period, 9 (18%) had major depression and 6 (11%) severe suicidality. Seven of these depressive patients also suffered from alcoholism. Sixty per cent of the patients were still on medication at the end of the follow-up. Depression, suicidality and alcoholism seem to be the long-term consequences of PD.

PMID 8739663  Acta Psychiatr Scand. 1996 Mar;93(3):181-3.
著者: R B Lydiard, M Steiner, D Burnham, I Gergel
雑誌名: Psychopharmacol Bull. 1998;34(2):175-82.
Abstract/Text The optimal assessment of treatment outcome for studies assessing the efficacy of treatments for panic disorder has been a controversial topic. A recent National Institute of Mental Health (NIMH)-sponsored consensus conference addressed this important topic, and a summary paper regarding assessment of essential elements of the disorder resulted. Among other conclusions, it was agreed that several different domains should be considered as essential. This article reviews three pivotal studies assessing the efficacy of paroxetine for the treatment of panic disorder, and evaluates these studies for inclusion of those variables considered essential. Additionally, some data were reanalyzed to determine the percentage of individuals in these studies who are unequivocal responders (i.e., were both panic-free and rated on global assessment as responders). A longer-term treatment and relapse study is also mentioned briefly.

PMID 9640997  Psychopharmacol Bull. 1998;34(2):175-82.
著者: C Marchesi, A Cantoni, S Fontò, M R Giannelli, C Maggini
雑誌名: Pharmacopsychiatry. 2006 Mar;39(2):60-5. doi: 10.1055/s-2006-931543.
Abstract/Text OBJECTIVE: In this naturalistic and prospective study, patients with panic disorder (PD) were treated for one year 1) to verify the rate of patients achieving the resolution of full-symptom attacks, limited-symptom attacks, anticipatory anxiety, phobic avoidance and depression; and 2) to identify the predictors of symptom resolution for each domain.
METHOD: One hundred patients with PD, according to DSM-IV criteria, participated in the study. In all patients, a baseline and a follow-up with monthly evaluations of SCL-90, Ham-A, Ham-D and panic diaries were carried out over a one-year period. All patients were treated with paroxetine or citalopram.
RESULTS: Seventy-one patients completed the study, whereas the remaining 29 dropped out. Among completers, remission of full- and limited-symptom panic attacks was observed in 76 % of patients, whereas complete remission (resolution of panic attacks, anticipatory anxiety, phobic anxiety, and depression) was achieved by only 46 % of patients. Predictors of absence of symptom remissions were obsessive-compulsive disorder (OCD) and recurrent major depression (MD) comorbidity (for panic attacks), pre-treatment severity of anxious symptoms (for anticipatory anxiety), phobic anxiety (for phobic avoidance), and depressive symptoms (for depression).
CONCLUSION: This naturalistic study shows that the high comorbidity of OCD and MD and the greater pre-treatment severity of anxious, phobic and depressive symptoms reduced the likelihood of achieving complete remission of symptoms in PD patients who completed the protocol, even though they were adequately treated with SSRI medication.

PMID 16555166  Pharmacopsychiatry. 2006 Mar;39(2):60-5. doi: 10.1055/s・・・
著者: D Michelson, M Pollack, R B Lydiard, R Tamura, R Tepner, G Tollefson
雑誌名: Br J Psychiatry. 1999 Mar;174:213-8.
Abstract/Text BACKGROUND: Data concerning appropriate treatment in panic disorder following an initial response to acute therapy are limited.
AIMS: To assess the safety and efficacy of continued fluoxetine treatment following successful acute therapy of panic disorder.
METHOD: Patients who responded to acute fluoxetine treatment were randomised to 24 weeks of continued fluoxetine or placebo.
RESULTS: Fluoxetine responders randomised to continue on their acute-phase fluoxetine dose experienced statistically significant improvement in panic attack frequency and phobia rating scale score over 24 weeks of therapy, while those switched to placebo experienced statistically significant worsening in Hamilton Anxiety (HAM-A), Hamilton Depression (HAM-D) and SCL-90-R rating scores.
CONCLUSIONS: Fluoxetine was associated with improved clinical outcomes compared with placebo during continuation therapy.

PMID 10448445  Br J Psychiatry. 1999 Mar;174:213-8.
著者: M H Rapaport, R Wolkow, A Rubin, E Hackett, M Pollack, K Y Ota
雑誌名: Acta Psychiatr Scand. 2001 Oct;104(4):289-98.
Abstract/Text OBJECTIVE: To investigate the long-term efficacy, prevention of relapse and safety of sertraline in the treatment of panic disorder.
METHOD: This study consisted of 52 weeks of open-label sertraline treatment (n=398) followed by a 28 weeks of a double-blind, placebo-controlled discontinuation trial (n=183).
RESULTS: Ninety-three patients were randomized to sertraline and 90 were randomized to placebo. Discontinuation due to insufficient clinical response occurred in 23.6% of placebo-treated patients and 12.0% of sertraline-treated patients (log-rank test, P=0.040). Thirty-three per cent of placebo-treated patients had an exacerbation of panic symptomatology, versus 13% of sertraline-treated patients (log-rank test, P=0.005). Abrupt cessation of sertraline resulted in dizziness (4.3% sertraline vs. 16.9% placebo; P=0.007) and insomnia (4.3% sertraline vs. 15.7% placebo; P=0.013) occurring at significantly higher rates.
CONCLUSION: Long-term sertraline treatment was effective in preventing relapse of panic disorder, well tolerated and associated with minimal discontinuation symptoms.

PMID 11722304  Acta Psychiatr Scand. 2001 Oct;104(4):289-98.
著者: M G Warshaw, A O Massion, M T Shea, J Allsworth, M B Keller
雑誌名: J Nerv Ment Dis. 1997 Aug;185(8):517-9.
Abstract/Text
PMID 9284866  J Nerv Ment Dis. 1997 Aug;185(8):517-9.
著者: V Starcevic
雑誌名: J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):19S-26S.
Abstract/Text In light of the mounting evidence that panic disorder (PD) tends to run a chronic or recurrent course, treatment goals for PD--both specific and general--have been reviewed and a model has been developed to assess the achievement of these goals over the long-term treatment of this disorder. The role of patient education in setting treatment goals has received special attention. The Goal-Oriented Monitoring and Assessment of the Efficacy of Treatment model measures the efficacy of treatment in terms of which treatment goals have been achieved and to what extent. Success of long-term treatment of PD depends on clear formulation of realistic treatment goals; implementation of effective treatment modalities for achieving these goals; maintenance of all treatment gains; prevention of relapses, recurrences, and complications; ensuring decreased vulnerability for PD and its exacerbations; and continuity of care. The Goal-Oriented Monitoring and Assessment of the Efficacy of Treatment model was used to assess the treatment of 118 patients at a day clinic. Patients were followed up for 24 months. Most treatment goals were achieved during the initial intensive, integrative treatment, with treatment gains being successfully maintained during follow-up. The model identified often-neglected patient needs that required particular attention over the course of treatment and during follow-up.

PMID 9872709  J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):19S-26S.・・・
著者: Jean-Marc Cloos
雑誌名: Curr Opin Psychiatry. 2005 Jan;18(1):45-50.
Abstract/Text PURPOSE OF REVIEW: The aim of this article is to provide an updated review of studies and recommendations published from August 2003 to August 2004 on the treatment of panic disorder.
RECENT FINDINGS: Cognitive-behavioral psychotherapy remains the treatment of choice for panic disorder. Recent studies confirm selective serotonin reuptake inhibitors as the first-choice drugs in treating panic disorder. Recommendations for (adjunctive) high-potency benzodiazepines have been published. Psychoeducation and combined pharmacotherapy/psychotherapy improve treatment response. Optimal long-term treatment of panic disorder involves adequate medication and duration of treatment, since relapse is frequent.
SUMMARY: Recent studies confirm that cognitive-behavioral therapy, alone or in combination with drug therapy, remains the treatment of choice for panic disorder. Long-term treatment is often necessary due to the chronicity of the illness.

PMID 16639183  Curr Opin Psychiatry. 2005 Jan;18(1):45-50.
著者: J R Davidson
雑誌名: J Clin Psychiatry. 1998;59 Suppl 8:17-21; discussion 22-3.
Abstract/Text Panic disorder is a chronic and recurring condition, and there is therefore a need for long-term therapy. This paper reviews data from long-term studies of drug treatment for panic disorder to address issues of whether medication benefits persist, whether improvement can continue over several months or years, the tolerability of long-term treatment, patient selection for long-term treatment, and when and how to stop medication. The main conclusion is that long-term drug treatment of panic disorder is necessary, effective, and safe. Serotonin selective reuptake inhibitors offer benefits of ease of dosing, good tolerability, and no safety or dependence problems; TCAs are often poorly tolerated, and benzodiazepines are associated with dependence problems. Withdrawal from all types of medication should be considered, slow, planned, and individualized; some patients require an indefinite duration of treatment.

PMID 9707158  J Clin Psychiatry. 1998;59 Suppl 8:17-21; discussion 22・・・
著者: Mark H Pollack, Christer Allgulander, Borwin Bandelow, Giovanni B Cassano, John H Greist, Eric Hollander, David J Nutt, Ahmed Okasha, Richard P Swinson, World Council of Anxiety
雑誌名: CNS Spectr. 2003 Aug;8(8 Suppl 1):17-30.
Abstract/Text What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzodiazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants have also shown antipanic efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. An integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long-term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended for at least 12-24 months, and in some cases, indefinitely.

PMID 14767395  CNS Spectr. 2003 Aug;8(8 Suppl 1):17-30.
著者: Pinhas N Dannon, Iulian Iancu, Ami Cohen, Katherine Lowengrub, Leon Grunhaus, Moshe Kotler
雑誌名: BMC Psychiatry. 2004 Jun 11;4:16. doi: 10.1186/1471-244X-4-16. Epub 2004 Jun 11.
Abstract/Text BACKGROUND: This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment, 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia, 3) To observe paroxetine's tolerability over a 24 month period.
METHODS: 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner.
RESULTS: Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase.
CONCLUSIONS: The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment.

PMID 15191617  BMC Psychiatry. 2004 Jun 11;4:16. doi: 10.1186/1471-244・・・
著者: Y Lecrubier, R Judge
雑誌名: Acta Psychiatr Scand. 1997 Feb;95(2):153-60.
Abstract/Text Paroxetine has been shown to be effective in panic disorder in three 10- to 12-week studies. This trial studied the longer term effects of paroxetine in patients with DSM-III-R defined panic disorder. Patients who satisfactorily completed a 12-week, double-blind, placebo-controlled study of paroxetine and clomipramine could choose to continue receiving their randomized treatment for a further 36 weeks. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. In total, 176 patients were included in the intention-to-treat population. The number of full panic attacks decreased in all three groups during the 12-week study, and improvements continued with long-term therapy. Paroxetine was statistically significantly more effective than placebo throughout the long-term study with respect to reduction from baseline of full panic attacks, and at the end of treatment with respect to the proportion of patients who eventually experienced no panic attacks. There were no significant differences between paroxetine and clomipramine. The proportion of patients who withdrew from the study due to adverse effects was greater in the clomipramine group (19%) than in either the paroxetine group (7%) or the placebo group (9%). Paroxetine was significantly more effective than placebo and as effective as (but better tolerated than) clomipramine in the long-term treatment of panic disorder. Not only was efficacy maintained, but continued improvement was also seen, indicating the importance of long-term treatment in patients with panic disorder.

PMID 9065681  Acta Psychiatr Scand. 1997 Feb;95(2):153-60.
著者: A W Goddard, T Brouette, A Almai, P Jetty, S W Woods, D Charney
雑誌名: Arch Gen Psychiatry. 2001 Jul;58(7):681-6.
Abstract/Text BACKGROUND: There is debate about combining benzodiazepines with selective serotonin reuptake inhibitors in the acute treatment of panic disorder. Although this medication combination is widely used in clinical practice, there is no well-tested, optimal method of coadministering these medications for the treatment of panic disorder. The purpose of this study was to test the efficacy of early coadministration of clonazepam with sertraline in the treatment of panic disorder.
METHODS: Fifty patients with panic disorder were randomized into a double-blind clinical trial. Patients received open-label sertraline for 12 weeks (target dose, 100 mg/d), and in addition were randomized to groups receiving either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks and discontinued.
RESULTS: Thirty-four (68%) of 50 patients completed the trial. Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam group (38% vs 25%) (P =.5). An intent-to-treat analysis (on last observation carried forward data) revealed a much greater proportion of responders in the sertraline/clonazepam compared with the sertraline/placebo group at the end of week 1 of the trial (41% vs 4%) (P =.003). There was also a significant between-group difference at the end of week 3 with 14 (63%) of 22 of the sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the sertraline/placebo group (P =.05). This difference was not observed at other times during the trial.
CONCLUSION: These data indicate that rapid stabilization of panic symptoms can be safely achieved with a sertraline/clonazepam combination, supporting the clinical utility of this type of regimen for facilitating early improvement of panic symptoms relative to sertraline alone.

PMID 11448376  Arch Gen Psychiatry. 2001 Jul;58(7):681-6.
著者: Mark H Pollack, Naomi M Simon, John J Worthington, Alicia L Doyle, Patricia Peters, Fany Toshkov, Michael W Otto
雑誌名: J Psychopharmacol. 2003 Sep;17(3):276-82.
Abstract/Text Despite the widespread application of combined selective serotonin reuptake inhibitors (SSRI) and benzodiazepine treatment for panic disorder, there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy. Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment, this study is the first to address the critical question of whether continued combined treatment confers superior efficacy. This study is a randomized, double-blind, three-arm study in patients with panic disorder (n = 60), comparing the efficacy and safety of paroxetine and placebo (PP), paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase (PC-D), and ongoing combination treatment (PC-M). All treatment groups demonstrated significant improvement by endpoint. There was a significant advantage for the combined treatment groups early in treatment but, subsequently, outcome in all three groups was similar. A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered. The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout. Combined treatment with paroxetine and clonazepam resulted in more rapid response than with the SSRI alone, but there was no differential benefit beyond the initial few weeks of therapy. Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy.

PMID 14513919  J Psychopharmacol. 2003 Sep;17(3):276-82.
著者: J B Herman, A W Brotman, J F Rosenbaum
雑誌名: J Clin Psychiatry. 1987 Oct;48 Suppl:22-8.
Abstract/Text Rebound--the relative worsening of symptoms on discontinuation of treatment as compared to baseline symptoms--is distinguished from withdrawal. Case reports and a clinical study are presented to illustrate the management of patients with panic disorder who are taking short- and intermediate-acting benzodiazepines and are experiencing rebound anxiety. The authors present the results of switching over to clonazepam 48 patients with panic disorder who were experiencing rebound effects with alprazolam. Eighty-two percent (39) of the patients rated clonazepam as being "better" than alprazolam due to decreased dosing frequency and lack of interdose anxiety. The authors conclude that clonazepam can be a useful alternative to alprazolam and other short-acting benzodiazepines in the treatment of anxiety disorders. Clonazepam offers the advantage of antipanic efficacy without the relative side effect problems seen with tricyclic antidepressants and monoamine oxidase inhibitors.

PMID 2889722  J Clin Psychiatry. 1987 Oct;48 Suppl:22-8.
著者: U M Lepola, R H Rimón, P J Riekkinen
雑誌名: Int Clin Psychopharmacol. 1993 Summer;8(2):115-8.
Abstract/Text Fifty-five patients with moderate to sever panic disorder were treated for 9 weeks with alprazolam or imipramine and were then, except for one patient who had committed suicide, re-examined after on average 3 years of treatment. At follow-up most patients (74%) did not suffer from panic attacks at all. In the beginning of the study 87% exhibited phobic avoidance behaviour but after 3 years 68% no longer revealed phobic behaviour. At follow-up 28% of the patients were no longer having psychotropic drug treatment and 20% were completely free of overt psychopathology. No tolerance phenomena were associated with the long-term medication applied in the study.

PMID 8345160  Int Clin Psychopharmacol. 1993 Summer;8(2):115-8.
著者: L M Nagy, J H Krystal, S W Woods, D S Charney
雑誌名: Arch Gen Psychiatry. 1989 Nov;46(11):993-9.
Abstract/Text Sixty patients with agoraphobia with panic attacks or panic disorder who completed a 4-month combined drug and behavioral group treatment program and were discharged on a regimen of alprazolam were interviewed 1.7 to 4 years (mean, 2.5 years) after discharge. At follow-up (FU), 18 (30%) of the patients had discontinued alprazolam treatment, 36 (60%) continued with a lower dose, 3 (5%) received the same dose, and 3 (5%) received an increased dose compared with discharge. A lower frequency of panic attacks at admission was associated with an increased ability to discontinue alprazolam treatment. There was little evidence of tolerance to the antipanic effects of alprazolam. Panic attack frequency dropped from a mean of 4.4 attacks per week at admission to 1.2 attacks per week at discharge and remained decreased at 1.6 attacks per week at FU. Treatment gains in the program were maintained or enhanced on 11 of 14 behavioral measures at FU and were similar in the groups that were receiving and not receiving alprazolam. Patients receiving nonpharmacologic therapy in the FU period tended to have greater symptom severity, possibly due to self-selection. A lifetime diagnosis of major depression at admission was associated with higher levels of depressive and anxiety symptoms and higher alprazolam doses at FU. Episodes of major depression were common in the FU period and did not appear to be prevented by initial alprazolam and behavioral therapy or by low-dose alprazolam maintenance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 2818144  Arch Gen Psychiatry. 1989 Nov;46(11):993-9.
著者: R Noyes, M J Garvey, B Cook, M Suelzer
雑誌名: Am J Psychiatry. 1991 Apr;148(4):517-23.
Abstract/Text OBJECTIVE: The purpose of this study was to compare the effects of discontinuing treatment with intermediate- and long-acting benzodiazepines.
METHOD: Fifty patients with panic disorder who had taken part in a double-blind treatment study and had responded to alprazolam, diazepam, or placebo for 8 months were asked to stop taking these medications gradually.
RESULTS: After a relatively rapid dose reduction, the majority of patients relapsed. Rebound anxiety and withdrawal symptoms were identified in a substantial minority of patients. Those who were taking alprazolam showed earlier and more intense rebound anxiety and withdrawal symptoms than did the patients who received diazepam. Both the level of pretreatment anxiety and the drug the patient was taking predicted the level of anxiety when drug treatment was discontinued.
CONCLUSIONS: The findings indicate that withdrawal phenomena commonly occur after patients stop taking benzodiazepines and that they are more frequent after discontinuation of treatment with shorter-acting drugs.

PMID 2006699  Am J Psychiatry. 1991 Apr;148(4):517-23.
著者: P P Roy-Byrne, S R Dager, D S Cowley, P Vitaliano, D L Dunner
雑誌名: Am J Psychiatry. 1989 Jul;146(7):860-5.
Abstract/Text The authors assessed the effects of partial tapering followed by abrupt discontinuation of alprazolam, diazepam, and placebo in 40 patients with panic attacks. The anxiety scores and frequency of panic attacks of the three groups did not differ at the end of the initial 2-week taper, but 1 week after abrupt discontinuation of the remaining medication, patients formerly taking alprazolam had greater increases in anxiety but no more panic attacks than did the other patients. Because of low statistical power, differences in benzodiazepine half-lives, absence of multiple ratings, and imbalances between groups in clinical characteristics, these findings must be viewed as preliminary.

PMID 2742010  Am J Psychiatry. 1989 Jul;146(7):860-5.
著者: E Schweizer, K Rickels, S Weiss, S Zavodnick
雑誌名: Arch Gen Psychiatry. 1993 Jan;50(1):51-60.
Abstract/Text One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder, panic disorder with limited phobic avoidance, or uncomplicated panic disorder entered an acute 8-week treatment phase. Patients who improved received an additional 6 months' maintenance treatment. Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase. During the maintenance phase, neither tolerance nor daily dose increase was observed. All patients who completed the maintenance phase (27 in the alprazolam group, 11 in the imipramine group, and 10 in the placebo group) were panic free at the end of 8 months of study treatment. Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg. Imipramine hydrochloride (175 mg/d) also produced significant panic relief but was associated with poor patient acceptance.

PMID 8422222  Arch Gen Psychiatry. 1993 Jan;50(1):51-60.
著者: K Rickels, E Schweizer
雑誌名: J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):12S-18S.
Abstract/Text This article compares panic disorder (PD) medications and discusses long-term therapy. In a review of the literature, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and benzodiazepines prove effective in treating PD. MAOIs treat comorbid depression; frequent side effects are dizziness and orthostatic hypotension. SSRIs are better tolerated than MAOIs, producing mild anticholinergic effects, but also producing gastrointestinal side effects and sexual dysfunction. Benzodiazepines are generally well tolerated when titrated gradually; moderate sedation is the most common short-term side effect. Long-term risks are physical dependence and withdrawal reactions. One hundred six PD patients were enrolled in a double-blind, 8-month, placebo-controlled trial of alprazolam and imipramine. In the 8-week short-term phase, daily dosages were titrated up to 10 mg/day of alprazolam and 250 mg/day of imipramine. The greatest number of dropouts occurred during this phase (lack of improvement and/or side effects). Alprazolam patients had a significantly more rapid onset of improvement and lower adverse events and attrition rates. In the 6-month maintenance period, patients continued short-term treatment. Patients receiving either alprazolam or imipramine developed tolerance to some side effects. At maintenance-phase completion, 62% of the alprazolam-group patients and 26% of both the imipramine- and placebo-group patients were panic free (p<0.01). Dosages were tapered to zero over 3 weeks; one third of the alprazolam patients could not discontinue. During the unblinded, 15-month follow-up, patients received open treatment selected by personal physicians on an as-needed basis. At the end of follow-up, all patients were reassessed. Patients who had completed both short-term and maintenance phases were far more likely to be panic-free (85% vs. 55%; p<0.01). PD is chronic and recurrent, and 8 months is an effective treatment period. Maintenance treatment does not lead to tolerance, even with benzodiazepines. Dose tapering must be very gradual. Completion of a long-term maintenance program strongly predicts remission.

PMID 9872708  J Clin Psychopharmacol. 1998 Dec;18(6 Suppl 2):12S-18S.・・・
著者: M Mavissakalian, J M Perel
雑誌名: Am J Psychiatry. 1992 Aug;149(8):1053-7.
Abstract/Text OBJECTIVE: This study was designed to assess and compare the differential relapse rates of patients with panic disorder and agoraphobia after discontinuation of acute treatment (6 months) or acute plus maintenance treatment (18 months) with imipramine.
METHOD: Sixteen patients with panic disorder and agoraphobia who had shown marked and stable response to 6 months of acute imipramine treatment and a comparable group of 14 patients who had been in remission during an additional year of half-dose imipramine maintenance treatment entered a 3-month, double-blind discontinuation study followed by a 3-month drug-free period. Assessments of the patients were made according to operationalized response/relapse criteria, and plasma drug concentrations were monitored.
RESULTS: Survival analysis revealed significantly different cumulative probabilities of continued response 6 months after discontinuation of imipramine treatment between the patients who had received only acute treatment and those who had received acute and maintenance treatment.
CONCLUSIONS: The results support the hypothesis that successful imipramine maintenance treatment of patients with panic and agoraphobia can have protective effects against relapse, at least in the first 6 months after the maintenance treatment period.

PMID 1636805  Am J Psychiatry. 1992 Aug;149(8):1053-7.
著者: K Black, C Shea, S Dursun, S Kutcher
雑誌名: J Psychiatry Neurosci. 2000 May;25(3):255-61.
Abstract/Text OBJECTIVE: To establish specific criteria by which selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome may be identified.
DATA SOURCES: MEDLINE and PSYCHLIT databases were searched for case reports published from 1986 to 1997 inclusive, and references of relevant articles were also searched.
STUDY SELECTION: Forty-six case reports of symptoms following the discontinuation of fluoxetine, fluvoxamine, paroxetine or sertraline were selected. Three studies of SSRI discontinuation were also reviewed.
DATA EXTRACTION: Demographic and treatment information, as well as the timing, duration, number, nature and frequency of dicontinuation symptoms.
DATA SYNTHESIS: Paroxetine was most frequently implicated. The drug had been tapered in half of the cases. In some cases, symptom onset began during taper, whereas, in most cases, symptoms began within 1 to 3 days of drug discontinuation. Fifty-three different symptoms were reported, with dizziness being the most common. Other common symptoms were nausea or emesis, fatigue, headache, gait instability and insomnia. Shock-like sensations, paresthesia and visual disturbances were the most rare. Without intervention, symptoms persisted for more than a week in half of the cases. In cases in which the SSRI was restarted, symptoms resolved within 72 hours. In some cases, withdrawal symptoms recurred when the same SSRI was again discontinued.
CONCLUSIONS: Findings were used to construct diagnostic criteria for the SSRI discontinuation syndrome. These criteria are 2 or more of the following symptoms developing within 1 to 7 days of discontinuation or reduction in dosage of an SSRI after at least 1 month's use, when these symptoms cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder: dizziness, light-headedness, vertigo or feeling faint; shock-like sensations or paresthesia; anxiety; diarrhea; fatigue; gait instability; headache; insomnia; irritability; nausea or emesis; tremor; and visual disturbances.

PMID 10863885  J Psychiatry Neurosci. 2000 May;25(3):255-61.
著者: I Hindmarch, S Kimber, S M Cockle
雑誌名: Int Clin Psychopharmacol. 2000 Nov;15(6):305-18.
Abstract/Text The abrupt discontinuation of antidepressants can result in a syndrome of adverse events, including somatic, mood and psychomotor reactions. This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors (SSRIs) on cognitive and psychomotor function. Eighty-seven patients receiving maintenance therapy with fluoxetine, sertraline, paroxetine or citalopram had their treatment interrupted for 4-7 days using double-blind placebo. Assessments of aspects of cognitive and psychomotor performance, mood and symptoms were carried out at each visit. Following interruption of treatment, significant differences between the groups emerged. Paroxetine treated patients experienced significantly more cognitive failures (P = 0.007), poorer quality of sleep (P = 0.016), and an increase in depressive symptoms, as rated both subjectively, using the Zung scale (P = 0.006) and by the clinician, using the Montgomery-Asberg Depression Rating Scale (P = 0.0003) and Clinical Global Impression (P = 0.0003), compared to some or all of the other drugs. All changes were reversed on reinstatement of treatment. Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning, which may be related to the antidepressant discontinuation syndrome. These effects are not evident in patients receiving fluoxetine, sertraline and citalopram, suggesting they are not an SSRI class phenomenon.

PMID 11110006  Int Clin Psychopharmacol. 2000 Nov;15(6):305-18.
著者: D Michelson, M Fava, J Amsterdam, J Apter, P Londborg, R Tamura, R G Tepner
雑誌名: Br J Psychiatry. 2000 Apr;176:363-8.
Abstract/Text BACKGROUND: Abrupt interruption of therapy with selective serotonin reuptake inhibitors (SSRIs) has been associated with somatic and psychological symptoms.
AIMS: Systematically to assess symptoms and effects on daily functioning related to interruption of SSRI therapy.
METHOD: Patients treated with fluoxetine, setraline or paroxetine underwent identical five-day periods of treatment interruption and continued active treatment under double-blind, order-randomised conditions, with regular assessment of new symptoms.
RESULTS: Placebo substitution for paroxetine was associated with increases in the number and severity of adverse events following the second missed dose, and increases in functional impairment at five days. Placebo substitution for sertraline resulted in less pronounced changes, while interruption of fluoxetine was not associated with any significant increase in symptomatology.
CONCLUSIONS: Abrupt interruption of SSRI treatment can result in a syndrome characterised by specific physical and psychological symptoms. Incidence, timing and severity of symptoms vary among SSRIs in a fashion that appears to be related to plasma elimination characteristics.

PMID 10827885  Br J Psychiatry. 2000 Apr;176:363-8.
著者: J F Rosenbaum, M Fava, S L Hoog, R C Ascroft, W B Krebs
雑誌名: Biol Psychiatry. 1998 Jul 15;44(2):77-87.
Abstract/Text BACKGROUND: Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness, insomnia, nervousness, nausea, and agitation. We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment, based on fluoxetine's longer half-life.
METHODS: In this 4-week study, 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine, sertraline, or paroxetine for 4-24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5-8 days. The Symptom Questionnaire (SQ), the Discontinuation-Emergent Signs and Symptoms checklist, the 28-item Hamilton Depression Rating Scale, and the Montgomery-Asberg Depression Rating Scale were used to assess somatic distress and stability of antidepressant response.
RESULTS: Two hundred twenty patients (91%) completed the study. Following interruption of therapy, fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients (p < .001). The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients (p < .001). Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients (p < .001).
CONCLUSIONS: Abrupt interruption of antidepressant therapy for 5-8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine.

PMID 9646889  Biol Psychiatry. 1998 Jul 15;44(2):77-87.

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