今日の臨床サポート

社交不安障害

著者: 松永寿人 兵庫医科大学 精神科

監修: 上島国利 昭和大学

著者校正/監修レビュー済:2022/03/30
参考ガイドライン:
日本不安症学会/日本神経精神薬理学会:社会不安症の診療ガイドライン 第1版(http://www.jsnp-org.jp/csrinfo/img/sad_guideline.pdf)
 
患者向け説明資料

概要・推奨   

  1. 社交不安障害(social anxiety disorder、 SAD)に対しては、国内で使用可能な4つのSSRI (フルボキサミン、パロキセチン、セルトラリン、エスシタロプラム)のいずれも、海外における多くの二重盲検比較試験において、プラセボに比べ有意な有効性が検証されているが、エビデンスの確実性は低く、弱い推奨となっている(推奨度2)。この中でわが国における適用を有するのは、フルボキサミンとパロキセチン、そしてエスシタロプラムであり、これらの薬剤が第一選択に提案されている。なおこれらは、添付文書に記載されている副作用の出現に注意し用いるべきとされている。
  1. SADに対する精神療法(心理的介入)では、SADに特化された個人療法による認知行動療法(cognitive behavioral therapy、CBT)を、これに習熟した治療者が一連の手順に基づいて行うことが、弱い推奨として提案されている(推奨度2)。もし患者が対面でのCBTを希望しない場合、CBTに基づくサポートつきのセルフヘルプを提案することが、弱く推奨されている(推奨度2)
  1. 一方、成人SAD患者に対する薬物療法と CBTの併用の実施に関しては、この有効性を支持するエビデンスは十分ではなく、それをする/しないに関しての推奨はなされていない。
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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
松永寿人 : 未申告[2022年]
監修:上島国利 : 原稿料(大日本住友製薬)[2022年]

改訂のポイント:「社会不安症の診療ガイドライン 第1版」に基づき治療について改訂を行った。

病態・疫学・診察

疾患情報  
  1. 社交不安障害(social anxiety disorder、 SAD)の中核的臨床像は、「恥ずかしい思いをするかもしれない社会的状況、または行為をする状況に対する顕著で持続的な恐怖」である。
  1. ICD-10では、「比較的少人数の集団内で、他の人々から注視される恐れ」が特徴とされる。
  1. 恐怖の対象は、人前で「話をする」、「字を書く」、「スポーツや楽器の演奏をする」など「行為をする状況」、あるいは「パーティーや結婚式に出席する」、「よく知らない人に会う」などの対人交流状況に大別される。
  1. このような状況への曝露により、ほとんどの場合は不安反応、例えば動悸、振戦、発汗、紅潮などが生じて、結果的にその状況を恐れ回避する。例えば手指の振戦などで恥をかくことを恐れ、人前での食事や書字などを避ける。
  1. 社交恐怖は、「あがり症」あるいは「内気」などの性格傾向とは異なり、恐怖や回避、またはその状況に直面する予期不安などによって、毎日の生活や職業的機能、社会生活などに著しい障害を来している、またはその恐怖による苦痛が顕著な場合においてのみ診断される。
  1. 成人においては、その恐怖の過剰性や不合理性を認識していることが必要である。
  1. このような恐怖が広範な社会的状況にみられ、通常は人前で行為をする状況、そして対人交流を持つ状況のいずれにも恐怖を感じている。
  1. パフォーマンス限局型の場合、恐怖する状況が、話したり演技をしたりなど、人前での行為状況に限定される。
  1. 回避性パーソナリティ障害との関連が強く、しばしば両者が併存する[1]
  1. パニック障害(広場恐怖を含む)、分離不安障害、広汎性発達障害などを鑑別する。
  1. 一般人口中における生涯有病率は、わが国では1.4%程度、欧米では2~12%とされている。
  1. 典型的な社交不安障害は、思春期、遅くても青年期までに発症する。
問診・診察のポイント  
  1. SADは、その有病率に比べ、受診率の低さが特徴である。

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 

Ted Reichborn-Kjennerud, Nikolai Czajkowski, Svenn Torgersen, Michael C Neale, Ragnhild E Ørstavik, Kristian Tambs, Kenneth S Kendler
The relationship between avoidant personality disorder and social phobia: a population-based twin study.
Am J Psychiatry. 2007 Nov;164(11):1722-8. doi: 10.1176/appi.ajp.2007.06101764.
Abstract/Text OBJECTIVE: The purpose of this study was to determine the sources of comorbidity for social phobia and dimensional representations of avoidant personality disorder by estimating to what extent the two disorders are influenced by common genetic and shared or unique environmental factors versus the extent to which these factors are specific to each disorder.
METHOD: Young adult female-female twin pairs (N=1,427) from the Norwegian Institute of Public Health Twin Panel were assessed at personal interview for avoidant personality disorder and social phobia using the Structured Interview for DSM-IV Personality and the Composite International Diagnostic Interview. Bivariate Cholesky models were fitted using the Mx statistical program.
RESULTS: The best-fitting model included additive genetic and unique environmental factors only. Avoidant personality disorder and social phobia were influenced by the same genetic factors, whereas the environmental factors influencing the two disorders were uncorrelated.
CONCLUSIONS: Within the limits of statistical power, these results suggest that there is a common genetic vulnerability to avoidant personality disorder and social phobia in women. An individual with high genetic liability will develop avoidant personality disorder versus social phobia entirely as a result of the environmental risk factors unique to each disorder. The results are in accordance with the hypothesis that psychobiological dimensions span the axis I and axis II disorders.

PMID 17974938
Katja Beesdo, Antje Bittner, Daniel S Pine, Murray B Stein, Michael Höfler, Roselind Lieb, Hans-Ulrich Wittchen
Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life.
Arch Gen Psychiatry. 2007 Aug;64(8):903-12. doi: 10.1001/archpsyc.64.8.903.
Abstract/Text CONTEXT: Epidemiological findings demonstrating an increased risk for individuals with social anxiety disorder (SAD) to develop depression have been challenged by discrepant findings from prospective longitudinal examinations in childhood and early adolescence.
OBJECTIVES: To examine patterns of SAD incidence, the consistency of associations of SAD with subsequent depression, and distal and proximal predictors for subsequent depression.
DESIGN: Face-to-face, 10-year prospective longitudinal and family study of up to 4 waves. The DSM-IV Munich-Composite International Diagnostic Interview was administered by clinically trained interviewers.
SETTING: Community sample in Munich.
PARTICIPANTS: Three thousand twenty-one individuals aged 14 to 24 years at baseline and 21 to 34 years at follow-up.
MAIN OUTCOME MEASURES: Cumulative incidence of SAD and depression (major depressive episode or dysthymia).
RESULTS: Cumulative incidence for SAD was 11.0%; for depression, 27.0%. Standardized person-years of incidence for SAD were highest for those aged 10 to 19 years (0.72%) and were low before (0.20%) and after (0.19%) that age range. Depression incidence was different, characterized by delayed and continued high rates. Social anxiety disorder was consistently associated with subsequent depression, independent of age at onset for SAD (relative risk range, 1.49-1.85, controlling for age and sex). Crude Cox regressions showed significant distal (eg, parental anxiety or depression, behavioral inhibition) and proximal SAD characteristics (eg, severity measures, persistence) as predictors. Most associations were attenuated in multiple models, leaving behavioral inhibition (hazard ratio, 1.30 [95% confidence interval, 1.04-1.62; P = .02]) and, less consistently, panic (hazard ratio, 1.85 [95% confidence interval, 1.08-3.18; P = .03]) as the remaining significant predictors.
CONCLUSIONS: Social anxiety disorder is an early, adolescent-onset disorder related to a substantially and consistently increased risk for subsequent depression. The demonstration of proximal and particularly distal predictors for increased depression risks requires further exploration to identify their moderator or mediator role. Along with previous evidence that comorbid SAD is associated with a more malignant course and character of depression, these results call for targeted prevention with the aim of reducing the burden of SAD and its consequences.

PMID 17679635
F R Schneier, T E Foose, D S Hasin, R G Heimberg, S-M Liu, B F Grant, C Blanco
Social anxiety disorder and alcohol use disorder co-morbidity in the National Epidemiologic Survey on Alcohol and Related Conditions.
Psychol Med. 2010 Jun;40(6):977-88. doi: 10.1017/S0033291709991231.
Abstract/Text BACKGROUND: To assess the prevalence and clinical impact of co-morbid social anxiety disorder (SAD) and alcohol use disorders (AUD, i.e. alcohol abuse and alcohol dependence) in a nationally representative sample of adults in the United States.
METHOD: Data came from a large representative sample of the US population. Face-to-face interviews of 43093 adults residing in households were conducted during 2001-2002. Diagnoses of mood, anxiety, alcohol and drug use disorders and personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule - DSM-IV version.
RESULTS: Lifetime prevalence of co-morbid AUD and SAD in the general population was 2.4%. SAD was associated with significantly increased rates of alcohol dependence [odds ratio (OR) 2.8] and alcohol abuse (OR 1.2). Among respondents with alcohol dependence, SAD was associated with significantly more mood, anxiety, psychotic and personality disorders. Among respondents with SAD, alcohol dependence and abuse were most strongly associated with more substance use disorders, pathological gambling and antisocial personality disorders. SAD occurred before alcohol dependence in 79.7% of co-morbid cases, but co-morbidity status did not influence age of onset for either disorder. Co-morbid SAD was associated with increased severity of alcohol dependence and abuse. Respondents with co-morbid SAD and alcohol dependence or abuse reported low rates of treatment-seeking.
CONCLUSIONS: Co-morbid lifetime AUD and SAD is a prevalent dual diagnosis, associated with substantial rates of additional co-morbidity, but remaining largely untreated. Future research should clarify the etiology of this co-morbid presentation to better identify effective means of intervention.

PMID 20441690
M R Liebowitz
Social phobia.
Mod Probl Pharmacopsychiatry. 1987;22:141-73.
Abstract/Text
PMID 2885745
Carlos Blanco, Muhammad S Raza, Franklin R Schneier, Michael R Liebowitz
The evidence-based pharmacological treatment of social anxiety disorder.
Int J Neuropsychopharmacol. 2003 Dec;6(4):427-42. doi: 10.1017/S1461145703003791.
Abstract/Text Social anxiety disorder (SAD) is a highly prevalent and often disabling disorder. This paper reviews the pharmacological treatment of SAD based on published placebo-controlled studies and published meta-analyses. It addresses three specific questions: What is the first-line treatment of SAD? How long should treatment last? What should be the management of treatment-resistant cases? Based on their efficacy for SAD and common comorbid disorders, tolerability, and safety, SSRIs should be considered as the first-line treatment for most patients. Less information is available regarding the optimal length of treatment, although individuals who discontinue treatment after 12-20 wk appear more likely to relapse than those who continue on medication. Even less empirical evidence is available to support strategies for treatment-resistant cases. Clinical experience suggests that SSRI non-responders may benefit from augmentation with benzodiazepines or gabapentin, or from switching to MAOIs, RIMAs, benzodiazepines or gabapentin. Cognitive-behavioural therapy may also be a helpful adjunct or alternative.

PMID 14609440
Carlos Blanco, Yang Xu, Franklin R Schneier, Mayumi Okuda, Shang-Min Liu, Richard G Heimberg
Predictors of persistence of social anxiety disorder: a national study.
J Psychiatr Res. 2011 Dec;45(12):1557-63. doi: 10.1016/j.jpsychires.2011.08.004. Epub 2011 Aug 27.
Abstract/Text Social anxiety disorder (SAD) is highly prevalent and impairing. Little is known about rates and predictors of persistence of SAD in the community. The current study derived data from the National Epidemiologic Survey on Alcohol and Related Conditions, Wave 1 (2001-2002, n = 43,093) and Wave 2 (2004-2005, n = 34,653), a large survey of a representative sample of the United States adult population. Individuals with current DSM-IV SAD at Wave 1 were re-interviewed 3 years later at Wave 2 using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM IV Version (AUDADIS-IV). We found that in the community, 22.3% of respondents with SAD at the Wave 1 evaluation met DSM-IV criteria for SAD three years later, and endorsement of social interaction fears and a higher number of avoided social situations, treatment-seeking during past year, and comorbidity with mood disorders independently predicted persistence of SAD. These results suggest that persistence of SAD in the community is common and associated with symptom severity and comorbid mood disorders.

Copyright © 2011. Published by Elsevier Ltd.
PMID 21875720
Dan J Stein, David S Baldwin, Borwin Bandelow, Carlos Blanco, Leonardo F Fontenelle, Sing Lee, Hisato Matsunaga, David Osser, Murray B Stein, Michael van Ameringen
A 2010 evidence-based algorithm for the pharmacotherapy of social anxiety disorder.
Curr Psychiatry Rep. 2010 Oct;12(5):471-7. doi: 10.1007/s11920-010-0140-8.
Abstract/Text A growing evidence base on the management of social anxiety disorder has yielded many meta-analyses and guidelines on the pharmacotherapy of this clinically important condition. We aimed to update a pharmacotherapy algorithm for the treatment of social anxiety disorder that was developed to be concise and user friendly and that was addressed to the primary care practitioner in particular. The updated algorithm attempts to summarize succinctly the recent literature in this area, as well as to include the views of an international panel of experts with diverse experience. The algorithm comprises eight sequential steps, beginning with those focused on diagnosis and initiating treatment and ending with the management of the treatment-refractory patient.

PMID 20686872
Noortje Vriends, Eni S Becker, Andrea Meyer, S Lloyd Williams, Rainer Lutz, Jürgen Margraf
Recovery from social phobia in the community and its predictors: data from a longitudinal epidemiological study.
J Anxiety Disord. 2007;21(3):320-37. doi: 10.1016/j.janxdis.2006.06.005. Epub 2006 Aug 17.
Abstract/Text The present longitudinal study aimed to determine rate of natural recovery from DSM-IV social phobia in the community and to examine predictors of recovery. Data were derived from the Dresden Predictor Study of a representative sample of 1396 young German women. The participants completed a diagnostic interview and self-report questionnaires at two survey points approximately 1.5 years apart. Of the 91 women with social phobia at baseline 64% were at least partially recovered and 36% showed full recovery from social phobia at follow-up, defined as absence of any of the DSM-IV criteria of social phobia. Predictors of recovery from social phobia were: being employed, no lifetime depression, fewer than three lifetime psychiatric disorders, less psychopathology, less anxiety sensitivity, fewer daily hassles, and better mental health. These results show that rates of recovery from social phobia are relatively high in community and that less stress and internal psychological problems play an important role in recovery from social phobia.

PMID 16919416
Carlos Blanco, Richard G Heimberg, Franklin R Schneier, David M Fresco, Henian Chen, Cynthia L Turk, Donna Vermes, Brigette A Erwin, Andrew B Schmidt, Harlan R Juster, Raphael Campeas, Michael R Liebowitz
A placebo-controlled trial of phenelzine, cognitive behavioral group therapy, and their combination for social anxiety disorder.
Arch Gen Psychiatry. 2010 Mar;67(3):286-95. doi: 10.1001/archgenpsychiatry.2010.11.
Abstract/Text CONTEXT: Medication and cognitive behavioral treatment are the best-established treatments for social anxiety disorder, yet many individuals remain symptomatic after treatment.
OBJECTIVE: To determine whether combined medication and cognitive behavioral treatment is superior to either monotherapy or pill placebo.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: Research clinics at Columbia University and Temple University.
PARTICIPANTS: One hundred twenty-eight individuals with a primary DSM-IV diagnosis of social anxiety disorder.
INTERVENTIONS: Cognitive behavioral group therapy (CBGT), phenelzine sulfate, pill placebo, and combined CBGT plus phenelzine.
MAIN OUTCOME MEASURES: Liebowitz Social Anxiety Scale and Clinical Global Impression (CGI) scale scores at weeks 12 and 24.
RESULTS: Linear mixed-effects models showed a specific order of effects, with steepest reductions in Liebowitz Social Anxiety Scale scores for the combined group, followed by the monotherapies, and the least reduction in the placebo group (Williams test = 4.97, P < .01). The CGI response rates in the intention-to-treat sample at week 12 were 9 of 27 (33.3%) (placebo), 16 of 34 (47.1%) (CBGT), 19 of 35 (54.3%) (phenelzine), and 23 of 32 (71.9%) (combined treatment) (chi(2)(1) = 8.76, P < .01). Corresponding remission rates (CGI = 1) were 2 of 27 (7.4%), 3 of 34 (8.8%), 8 of 35 (22.9%), and 15 of 32 (46.9%) (chi(2)(1) = 15.92, P < .01). At week 24, response rates were 9 of 27 (33.3%), 18 of 34 (52.9%), 17 of 35 (48.6%), and 25 of 32 (78.1%) (chi(2)(1) = 12.02, P = .001). Remission rates were 4 of 27 (14.8%), 8 of 34 (23.5%), 9 of 35 (25.7%), and 17 of 32 (53.1%) (chi(2)(1) = 10.72, P = .001).
CONCLUSION: Combined phenelzine and CBGT treatment is superior to either treatment alone and to placebo on dimensional measures and on rates of response and remission.

PMID 20194829
Richard A Hansen, Bradley N Gaynes, Gerald Gartlehner, Charity G Moore, Ruchi Tiwari, Kathleen N Lohr
Efficacy and tolerability of second-generation antidepressants in social anxiety disorder.
Int Clin Psychopharmacol. 2008 May;23(3):170-9. doi: 10.1097/YIC.0b013e3282f4224a.
Abstract/Text A systematic review and meta-analysis were conducted to evaluate the comparative efficacy and tolerability of second-generation antidepressants in social anxiety disorder. Studies were identified by searching MEDLINE, Embase, The Cochrane Library, PsychLit, and the International Pharmaceutical Abstracts from January 1980 through October 2006. Comparative evidence was summarized and indirect comparisons were made using network meta-analysis. Only three head-to-head trials were identified; comparative trials found only minimal differences in efficacy between escitalopram and paroxetine, and no statistically significant differences in efficacy between extended-release venlafaxine and paroxetine. Pooled evidence from 15 placebo-controlled trials suggests that escitalopram [relative benefit (RB) 1.3; 95% confidence interval (CI) 1.2-1.5], paroxetine (RB 1.9; 95% CI 1.5-2.3), sertraline (RB 1.8; 95% CI 1.5-2.2), and venlafaxine (RB 1.7; 95% CI 1.5-1.9) all produce significantly more responders than placebo; evidence favored fluvoxamine over placebo but was not significant (RB 1.5; 95% CI 0.9-2.4). Network meta-analysis did not reveal differences in efficacy among drugs. Overall, a fair amount of evidence supports the efficacy of escitalopram, fluvoxamine, paroxetine, sertraline, and venlafaxine in social anxiety disorder. The drugs do not differ in efficacy, although their adverse event profiles do.

PMID 18408531
Stefano Pallanti, Leonardo Quercioli
Resistant social anxiety disorder response to Escitalopram.
Clin Pract Epidemiol Ment Health. 2006 Dec 13;2:35. doi: 10.1186/1745-0179-2-35. Epub 2006 Dec 13.
Abstract/Text BACKGROUND: Social Anxiety Disorder (SAD) is a common disorder and its high prevalence and lifelong chronicity are such that it represents a substantial public health problem. The observation that serotonergic agents appear to be effective for its treatment suggests that patients may have abnormal serotonergic neurotransmission within the central nervous system. We investigated the efficacy of Escitalopram in treatment resistant patients with SAD.
METHOD: Twenty-nine adult outpatients participated in a 12-week open-label trial of escitalopram. All the subjects had a primary diagnosis of SAD and had failed at least one previous adequate trial of paroxetine. Escitalopram was orally administered starting with a dose of 10 mg/day following a 1-week titration.
RESULTS: The escitalopram treatment was characterized by good tolerability (drop-out rate due to intolerance: 10.3%), and 24 subjects completed the study trial. At the end of the 12-week treatment period, 14 subjects (48.3%) were considered as responders on the basis of the Clinical Global Impression-Improvement (CGI-I) (much or very much improved) scale and the Liebowitz Scale for Social Anxiety (LSAS) (reduction >35% compared to baseline). We observed a significant mean reduction in the Sheehan Disability Scale Work (p < .05) and Social (p < .05) subscores, but not in the Family subscore.
CONCLUSION: These data suggest escitalopram has a role in the treatment of resistant SAD, especially in view of the favourable tolerability profile observed in the patients. Controlled studies are required to further investigate these findings and to compare escitalopram with other treatments for this disorder.

PMID 17166264
Michael Van Ameringen, Catherine Mancini, Beth Patterson, Mark Bennett
An evaluation of paroxetine in generalised social anxiety disorder.
Expert Opin Pharmacother. 2005 May;6(5):819-30. doi: 10.1517/14656566.6.5.819.
Abstract/Text It is estimated that social anxiety disorder affects approximately 13.3% individuals within the community at some point in their lifetime and is associated with significant functional impairment. A variety of drug groups have demonstrated efficacy in treating social anxiety disorder, including selective serotonin reuptake inhibitors (SSRIs). Paroxetine is an SSRI approved by the FDA and Health Canada for the treatment of a variety of psychiatric conditions. Paroxetine has been the most studied agent in social anxiety disorder and has been shown to be effective in short-term, fixed- and flexible-dose placebo-controlled trials, as well as in long-term treatment. The pharmacotherapy of social phobia will be reviewed, with a special focus on investigations with paroxetine.

PMID 15934907
M B Stein, A J Fyer, J R Davidson, M H Pollack, B Wiita
Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study.
Am J Psychiatry. 1999 May;156(5):756-60.
Abstract/Text OBJECTIVE: The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder).
METHOD: In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of "much improved" or "very much improved" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale.
RESULTS: The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe.
CONCLUSIONS: These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia.

PMID 10327910
Satoshi Asakura, Osamu Tajima, Tsukasa Koyama
Fluvoxamine treatment of generalized social anxiety disorder in Japan: a randomized double-blind, placebo-controlled study.
Int J Neuropsychopharmacol. 2007 Apr;10(2):263-74. doi: 10.1017/S1461145706006602. Epub 2006 Mar 30.
Abstract/Text The efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of social anxiety disorder (SAD) has been reported in the USA and Europe. However, no clinical investigation has been done with SSRIs in Japanese patients with SAD. This study was performed to determine the effectiveness and safety of fluvoxamine for generalized SAD (GSAD) in Japanese patients. In this double-blind study, patients meeting DSM-IV criteria for GSAD were randomized to receive treatment with fluvoxamine or placebo for 10 wk. Fluvoxamine treatment was initiated at 50 mg/d, and increased by 50 mg weekly to a maximum of 150 or 300 mg/d. The primary efficacy outcome was mean change from baseline on the Liebowitz Social Anxiety Scale - Japanese Version (LSAS-J) total score. The secondary outcomes were response according to the Clinical Global Impressions - Global Improvement (CGI-I) score and three domains of the Sheehan Disability Scale (SDS; used to assess psychosocial impairment). A total of 176 fluvoxamine-treated patients and 89 placebo-treated patients were eligible for the efficacy analysis. At week 10, the fluvoxamine-treated patients had a significantly greater reduction in the LSAS-J total score compared with placebo-treated patients (p=0.0197), with significantly more fluvoxamine recipients being at least much improved on the CGI-I scale compared with placebo-treated patients (p=0.024). Fluvoxamine-treated patients also had better responses on the SDS compared with placebo-treated patients (p=0.0208). Fluvoxamine was safe and well tolerated. These results suggest that fluvoxamine is effective for the treatment of Japanese patients with GSAD.

PMID 16573847
Dan J Stein, Murray B Stein, Cornelius D Pitts, Rajinder Kumar, Brian Hunter
Predictors of response to pharmacotherapy in social anxiety disorder: an analysis of 3 placebo-controlled paroxetine trials.
J Clin Psychiatry. 2002 Feb;63(2):152-5.
Abstract/Text BACKGROUND: There is increasing evidence that patients with social anxiety disorder (social phobia) respond to treatment with selective serotonin reuptake inhibitors (SSRIs). Response rates to SSRIs in social anxiety disorder have ranged from at least 50% in controlled trials to up to 80% in open trials. To date, however, there has been little information available about predictors of response to treatment in this disorder.
METHOD: Data from 3 placebo-controlled multicenter trials of paroxetine in DSM-IV social anxiety disorder (N = 829) were analyzed using logistic regression to determine predictors of response. Demographic (age, sex), physiologic (baseline heart rate, baseline mean arterial pressure), clinical (baseline social anxiety symptom severity, baseline disability, duration of illness), and trial variables (paroxetine dose, treatment duration) were included.
RESULTS: Only duration of treatment was a statistically significant predictor of treatment response. Further analysis demonstrated that, in paroxetine-treated patients in particular, many nonresponders at week 8 (46/166; 27.7%) were responders at week 12.
CONCLUSION: These data demonstrate that paroxetine is a reasonable choice of treatment in a broad spectrum of patients with social anxiety disorder. An optimal trial of medication should continue beyond 8 weeks.

PMID 11874217
M Van Ameringen, C Mancini
Pharmacotherapy of social anxiety disorder at the turn of the millennium.
Psychiatr Clin North Am. 2001 Dec;24(4):783-803.
Abstract/Text Over the past 21 years since the birth of SP into the diagnostic nomenclature, there have been significant gains in knowledge about effective pharmacologic and psychotherapeutic treatments. The SSRIs have emerged as the first-line pharmacologic treatment, although good evidence shows efficacy of benzodiazepines; MAOIs; and anticonvulsant agents, such as gabapentin and pregabalin. There is also emerging evidence about the efficacy of the novel antidepressant venlafaxine and also optimism for the potential utility of nefazodone and possibly bupropion. However, there are many areas requiring further investigation. There has been a great deal of excitement about the publication of the RUPP Anxiety Study, demonstrating efficacy for fluvoxamine in socially phobic youth. Given that SP starts in childhood and adolescence, more data are needed to support the use of pharmacotherapy in this age group because early intervention may prevent the sequelae of chronic SP. There needs to be more investigation into what is required for social phobic individuals who obtain a good response to pharmacotherapy to move into full-remission status. Additional research is needed regarding the evaluation of the comparative efficacy of different drug classes and to develop an improved capability of predicting treatment response to a particular type of treatment. In addition, more research is needed regarding treatment resistance. In most of the anxiety disorders that have been studied, combining CBT with psychopharmacologic treatment has shown little advantage over either treatment alone. These findings may be due to methodologic problems. Research is needed on how to sequence treatments to maximize the benefits of combining the two types of effective treatments together. Finally, many clinicians are seeing an emerging trend of individuals who have had untreated SP all of their lives and are now presenting for treatment in their "golden years." The current established treatments need to be evaluated further in this geriatric population.

PMID 11723633
J R Davidson, N Potts, E Richichi, R Krishnan, S M Ford, R Smith, W H Wilson
Treatment of social phobia with clonazepam and placebo.
J Clin Psychopharmacol. 1993 Dec;13(6):423-8.
Abstract/Text Clonazepam and placebo were administered in a double-blind pilot study to 75 outpatients with social phobia. The mean maximum dose of clonazepam was 2.4 mg/day at endpoint (range, 0.5 to 3 mg). Treatment was continued for up to 10 weeks. The results of an intent-to-treat analysis indicated superior effects of clonazepam on most measures. Response rates for clonazepam and placebo were 78.3 and 20.0%. Drug effects were apparent on performance and generalized social anxiety, on fear and phobic avoidance, on interpersonal sensitivity, on fears of negative evaluation, and on disability measures. Significant differences were evident by week 1, 2, or 6, depending upon the rating scale used. Clonazepam was well tolerated in general, although unsteadiness and dizziness were more severe and persistent than was the case for placebo subjects.

PMID 8120156
I C Fedoroff, S Taylor
Psychological and pharmacological treatments of social phobia: a meta-analysis.
J Clin Psychopharmacol. 2001 Jun;21(3):311-24.
Abstract/Text A meta-analysis of psychological and pharmacological treatments for social phobia was conducted to evaluate whether the various treatments differ in their efficacy for treating social phobia, whether they are more effective than wait-list and placebo controls, whether rates of attrition differ, and whether treatment gains are maintained at follow-up. A total of 108 treatment-outcome trials for social phobia met inclusion/exclusion criteria for the meta-analysis. Eleven treatment conditions were compared: wait-list control, pill placebo, benzodiazepines (BDZs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors, attention placebo, exposure (EXP), cognitive restructuring (CR), EXP plus CR, social skills training, and applied relaxation. The most consistently effective treatments for social phobia were pharmacotherapies. BDZs and SSRIs were equally effective and more effective than control conditions. Dropout rates were similar among all the active treatment conditions. Assessment of the durability of treatment gains for pharmacotherapies was not possible because an insufficient number of drug studies included follow-up data. The treatment gains of psychological therapies, although moderate, continued during the follow-up period. BDZs and SSRIs seem to be effective treatments for social phobia, at least in the short term. Recommendations for future research include assessing the long-term outcome for pharmacotherapies and evaluating the inclusion of a cognitive-behavioral treatment during the drug tapering period.

PMID 11386495
Carlos Blanco, Franklin R Schneier, Andrew Schmidt, Carmen-Rosa Blanco-Jerez, Randall D Marshall, Arturo Sánchez-Lacay, Michael R Liebowitz
Pharmacological treatment of social anxiety disorder: a meta-analysis.
Depress Anxiety. 2003;18(1):29-40. doi: 10.1002/da.10096.
Abstract/Text Placebo-controlled trials have evaluated the efficacy of several medications in the treatment of social anxiety disorder but information regarding their relative efficacy is lacking. We compared the efficacy of medications systematically studied for the treatment of social anxiety disorder using meta-analytic techniques. The methodology included a database search of articles published between January 1980 and June 2001 and manual searches of bibliographies in published manuscripts. Trials were included if they reported outcome data on the Liebowitz Social Anxiety Scale (LSAS) or a categorical measure of responder status. Data were extracted independently by two authors. The Q statistic was used to assess homogeneity across trials. All analyses were conducted using intent-to-treat data. There was substantial heterogeneity across trials. The medications with largest effect sizes were phenelzine [effect size, 1.02; 95% Confidence Interval (CI), 0.52-1.52], clonazepam (effect size, 0.97; 95% CI, 0.49-1.45), gabapentin (effect size, 0.78; 95% CI, 0.29-1.27), brofaromine (effect size, 0.66; 95% CI, 0.38-0.94), and the selective serotonin reuptake inhibitors (SSRIs; effect size, 0.65; 95% CI, 0.50-0.81). There were no statistically significant differences between medications or medication groups. However, formal methods of interim monitoring adapted for meta-analyses suggested strongest evidence of efficacy for SSRIs and brofaromine. Several medications are efficacious for the treatment of social anxiety disorder. The stability of the SSRI effect size estimate in conjunction with other evidence for safety and tolerability and their ability to treat comorbid conditions supports the use of SSRIs as the first-line treatment. Direct comparisons of SSRIs vs. other promising medications deserve consideration.

Copyright 2003 Wiley-Liss, Inc.
PMID 12900950
Steven E Bruce, Kimberly A Yonkers, Michael W Otto, Jane L Eisen, Risa B Weisberg, Maria Pagano, M Tracie Shea, Martin B Keller
Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study.
Am J Psychiatry. 2005 Jun;162(6):1179-87. doi: 10.1176/appi.ajp.162.6.1179.
Abstract/Text OBJECTIVE: The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder, generalized anxiety disorder, and social phobia.
METHOD: Data were drawn from the Harvard/Brown Anxiety Disorders Research Program, a prospective, naturalistic, longitudinal, multicenter study of adults with a current or past history of anxiety disorders. Probabilities of recovery and recurrence were calculated by using standard survival analysis methods. Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence.
RESULTS: Survival analyses revealed an overall chronic course for the majority of the anxiety disorders. Social phobia had the smallest probability of recovery after 12 years of follow-up. Moreover, patients who had prospectively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period. The overall clinical course was worsened by several comorbid psychiatric conditions, including major depression and alcohol and other substance use disorders, and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia.
CONCLUSIONS: These data depict the anxiety disorders as insidious, with a chronic clinical course, low rates of recovery, and relatively high probabilities of recurrence. The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence. The findings add to the understanding of the nosology and treatment of these disorders.

PMID 15930067
Wenbin Liang, Tanya Chikritzhs
Affective disorders, anxiety disorders and the risk of alcohol dependence and misuse.
Br J Psychiatry. 2011 Sep;199(3):219-24. doi: 10.1192/bjp.bp.110.086116. Epub 2011 Jun 27.
Abstract/Text BACKGROUND: It is unclear whether common affective disorders and anxiety disorders increase the risk of alcohol dependence and alcohol misuse. Aims To investigate whether affective disorders and anxiety disorders increase the risk of alcohol dependence and alcohol misuse.
METHOD: This study is a retrospective cohort study based on data collected from the 2007 Australia Mental Health and Well-Being survey. Both Poisson and logistic regression models were used for multivariate analysis.
RESULTS: Participants with affective disorders (relative risk (RR) = 5.46, 95% CI 4.08-7.31 for alcohol dependence within 5 years of onset; RR = 2.77, 95% CI 1.93-3.99 after first 5 years) and anxiety disorders (RR = 3.33, 95% CI 2.37-4.68 for alcohol dependence within first 5 years of onset; RR = 3.56, 95% CI 2.72-4.64 after first 5 years) were at higher risk of alcohol misuse and alcohol dependence.
CONCLUSIONS: Common affective disorders and anxiety disorders may increase the risk of alcohol dependence and alcohol misuse among the Australian population.

PMID 21708880
M B Stein, M J Chartier, A L Hazen, C D Kroft, R A Chale, D Coté, J R Walker
Paroxetine in the treatment of generalized social phobia: open-label treatment and double-blind placebo-controlled discontinuation.
J Clin Psychopharmacol. 1996 Jun;16(3):218-22.
Abstract/Text We conducted an 11-week forced-escalation open-label study of paroxetine in the treatment of 36 patients with generalized social phobia. At the mean dosage of 47.9 +/- 6.2 mg/day, 23 of 30 completers (77%) were deemed responders on the basis of a clinician rating of either "very much improved" or "much improved" on the Clinical Global Impressions scale. Duke Social Phobia Scale ratings declined from 35.5 +/- 13.1 at baseline to 19.7 +/- 17.4 at week 11 (p < 0.0005), and Liebowitz Social Anxiety Scale ratings declined from 75.1 +/- 25.4 at baseline to 37.2 +/- 32.5 at week 11 (p < 0.0005). Sixteen responders were randomized to an additional 12 weeks of either paroxetine (with no dosage change) or placebo (after a taper period) on a double-blind basis. To the best of our knowledge, this is the first controlled medication-discontinuation study in social phobia. One of eight patients randomized to continue paroxetine relapsed versus five of eight patients randomized to placebo. These findings call for a double-blind, placebo-controlled treatment study of paroxetine in generalized social phobia. They also suggest that relapse rates are high if medication is discontinued early and that further study is needed to determine (1) the optimal duration of maintenance pharmacotherapy for social phobia and (2) if specific psychotherapeutic interventions before medication discontinuation may prevent relapse.

PMID 8784653
Dan J Stein, Marcio Versiani, Tanya Hair, Rajinder Kumar
Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study.
Arch Gen Psychiatry. 2002 Dec;59(12):1111-8.
Abstract/Text BACKGROUND: The efficacy of selective serotonin reuptake inhibitors in the acute treatment of social anxiety disorder (social phobia) is well established.
OBJECTIVE: To evaluate whether the efficacy of paroxetine hydrochloride in this disorder is maintained in the long term.
METHODS: This was a placebo-controlled multicenter study comprising a single-blind acute treatment phase (12 weeks) and a randomized, double-blind maintenance treatment phase (24 weeks) for patients who had responded to paroxetine during the acute phase. Four hundred thirty-seven adult patients with social anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, code 300.23) entered the acute phase, and 323 continued into the maintenance phase (162 paroxetine and 161 placebo). The principal outcome measure was the proportion of patients relapsing during the maintenance phase.
RESULTS: Two hundred fifty-seven patients completed the study (136 paroxetine-treated and 121 placebo-treated patients). Significantly fewer patients relapsed in the paroxetine group than in the placebo group (14% vs 39%; odds ratio, 0.24; 95% confidence interval, 0.14-0.43; P<.001). At the end of the study, a significantly greater proportion of patients in the paroxetine group showed improvement as shown on the Clinical Global Impression global improvement rating compared with the placebo group (78% vs 51%; odds ratio, 3.66; 95% confidence interval, 2.22-6.04; P<.001). Compared with placebo, paroxetine treatment significantly (P<.001) improved the symptoms of social anxiety as shown on the Liebowitz Social Anxiety Scale, Social Phobia Inventory, Sheehan Disability Scale, Symptom Checklist-90 score, and EuroQol visual analogue scale, indicating decreased disability and increased well-being. Paroxetine was well tolerated.
CONCLUSION: Paroxetine is an effective long-term treatment for social anxiety disorder.

PMID 12470127

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