{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:15:19Z","timestamp":1778310919794,"version":"3.51.4"},"reference-count":91,"publisher":"Cambridge University Press (CUP)","issue":"10","license":[{"start":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T00:00:00Z","timestamp":1415318400000},"content-version":"unspecified","delay-in-days":3689,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS spectr."],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Over the last 25 years, there has been a rapid expansion of our knowledge base of social phobia (SP). Although there are a number of well-validated treatment modalities, including pharmacotherapy and cognitive-behavioral therapy, significant gaps remain in our ability to achieve full remission in most patients. Despite advances in the neurobiology of SP, the etiology has yet to be determined. Investigations examining potential predictors of response have provided little guidance in selecting an appropriate treatment modality. These gaps in our knowledge have pushed us to examine issues related to treatment resistance. This paper presents a review of the current literature and issues related to treatment-resistant SP, including a discussion of the functional impairment associated with SP, definitions of treatment response and remission, as well as outcome measures that have been used in clinical investigations of SP. In addition, criteria for a standard treatment trial, predictors of treatment response, a review of treatment resistance studies, and potential directions for future research are examined. The most promising strategies to attain remission, will likely involve augmenting selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors with agents such as anticonvulsants, benzodiazepines, and antipsychotics as well as combining pharmacotherapy with cognitive-behavioral therapy. Our current treatment target of simply attaining a response needs to be refocused, so that an asymptomatic state and high end state functioning become the final goal of treatment.<\/jats:p>","DOI":"10.1017\/s1092852900022392","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T04:39:50Z","timestamp":1470112790000},"page":"753-762","source":"Crossref","is-referenced-by-count":33,"title":["Optimizing Treatment in Social Phobia: A Review of Treatment Resistance"],"prefix":"10.1017","volume":"9","author":[{"given":"Michael","family":"Van Ameringen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Pipe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2014,11,7]]},"reference":[{"key":"S1092852900022392_ref090","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6394(2000)11:1<45::AID-DA8>3.0.CO;2-8"},{"key":"S1092852900022392_ref088","first-page":"181","volume-title":"Social Anxiety Disorder","author":"Van Ameringen","year":"2004"},{"key":"S1092852900022392_ref087","unstructured":"Hoge EA , Reese HE , Doyle AC , et al. Risperidone for the treatment of refractory panic, social anxiety, and generalized anxiety disorders. Poster presented at: annual meeting of the Anxiety Disorders Association of America. March 11-14, 2004; Miami, FL."},{"key":"S1092852900022392_ref086","doi-asserted-by":"publisher","DOI":"10.1177\/026988110201600412"},{"key":"S1092852900022392_ref085","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-200302000-00015"},{"key":"S1092852900022392_ref084","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.10.1777"},{"key":"S1092852900022392_ref082","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-200107000-00003"},{"key":"S1092852900022392_ref078","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(97)87395-7"},{"key":"S1092852900022392_ref077","article-title":"An opentrial of topiramate in generalized social phobia","author":"Van Ameringen","journal-title":"J Clin Psychiatryjt"},{"key":"S1092852900022392_ref076","article-title":"Levetiracetam for the treatment of social anxiety disorder","author":"Simon","journal-title":"J Clin Psychiatry"},{"key":"S1092852900022392_ref074","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(02)00018-4"},{"key":"S1092852900022392_ref072","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810250064008"},{"key":"S1092852900022392_ref071","unstructured":"Heimberg RG . Cognitive behavioral and psychotherapeutic strategies for social anxiety disorder. Paper presented at: annual meeting of the Anxiety Disorders Association of America. March 27-30, 2003; Toronto, Canada."},{"key":"S1092852900022392_ref070","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-200206000-00005"},{"key":"S1092852900022392_ref069","unstructured":"Foa EM , Davidson JRT , Huppert JD , et al. Comprehensive CBT, fluoxetine, and their combination: a randomized placebo-controlled trial. Paper presented at: annual meeting of the Association for the Advancement of Behavior Therapy. November 20-23, 2003; Boston, Mass."},{"key":"S1092852900022392_ref067","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.182.4.312"},{"key":"S1092852900022392_ref063","first-page":"27","article-title":"Treatment of social phobia by endoscopic thoracic sympathicotomy","volume":"580","author":"Telaranta","year":"1998","journal-title":"Eur J Surg"},{"key":"S1092852900022392_ref062","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.3.513"},{"key":"S1092852900022392_ref057","unstructured":"Kinrys G , Soldani F , Hsu D , et al. Adjunctive tiagabine for treatment refractory social anxiety disorder. Poster presented at: annual meeting of the American Psychiatric Association. May 1-6, 2004; New York, NY."},{"key":"S1092852900022392_ref056","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(96)00030-4"},{"key":"S1092852900022392_ref052","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(86)90105-8"},{"key":"S1092852900022392_ref051","doi-asserted-by":"publisher","DOI":"10.1016\/0005-7967(90)90001-Y"},{"key":"S1092852900022392_ref060","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-2406.2003.00061.x"},{"key":"S1092852900022392_ref047","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.5.434"},{"key":"S1092852900022392_ref046","doi-asserted-by":"publisher","DOI":"10.1097\/01.jcp.0000104909.75206.6f"},{"key":"S1092852900022392_ref044","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(98)00093-7"},{"key":"S1092852900022392_ref041","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199612000-00003"},{"key":"S1092852900022392_ref035","unstructured":"Stein DJ , Hunter B , Rolfe T , et al. Paroxetine in social anxiety disorder: a remission analysis. Poster presented at: annual meeting of the European College of Neuropsychopharmacology Congress. October 5-9, 2002; Barcelona, Spain."},{"key":"S1092852900022392_ref034","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1017\/S0033291701004020","article-title":"Long-term outcome of social phobia treated by exposure","volume":"31","author":"Fava","year":"2001","journal-title":"Psychol Med"},{"key":"S1092852900022392_ref037","doi-asserted-by":"publisher","DOI":"10.1185\/135525701317094368"},{"key":"S1092852900022392_ref013","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1176\/ajp.156.5.756","article-title":"Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study","volume":"156","author":"Stein","year":"1995","journal-title":"Am J Psychiatry"},{"key":"S1092852900022392_ref014","unstructured":"Davidson JRT , Hemby LW , Barbato L , et al. Fluvoxamine controlled release for the treatment of generalized social anxiety disorder. Poster presented at: annual meeting of the American College of Neuropsychopharmacology. December 10-14, 2000; San Juan, Puerto Rico."},{"key":"S1092852900022392_ref028","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.12.1999"},{"key":"S1092852900022392_ref064","doi-asserted-by":"publisher","DOI":"10.1080\/08039480310000266"},{"key":"S1092852900022392_ref065","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01183-0"},{"key":"S1092852900022392_ref049","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-200201000-00010"},{"key":"S1092852900022392_ref075","unstructured":"Papp LA , Ninan PT . Tiagabine for the treatment of social anxiety disorder. Paper presented at: annual meeting of the American Psychiatric Association. May 1-6, 2004. New York, NY."},{"key":"S1092852900022392_ref073","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1176\/ajp.156.11.1833","article-title":"Adjunctive lamotrigine treatment for major depression","volume":"156","author":"Maltese","year":"1999","journal-title":"Am J Psychiatry"},{"key":"S1092852900022392_ref007","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1995.tb09596.x"},{"key":"S1092852900022392_ref055","doi-asserted-by":"publisher","DOI":"10.1080\/08039480310002110"},{"key":"S1092852900022392_ref004","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810340070009"},{"key":"S1092852900022392_ref059","first-page":"20","article-title":"Refractory obsessive-compulsive disorder: state-of-the-art treatment","volume":"63","author":"Hollander","year":"2002","journal-title":"J Clin Psychiatry"},{"key":"S1092852900022392_ref023","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199908000-00010"},{"key":"S1092852900022392_ref048","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-6185(97)00008-X"},{"key":"S1092852900022392_ref032","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(03)00231-2"},{"key":"S1092852900022392_ref022","unstructured":"Stein MB , Pollack MH , Mangano R . Long-term treatment of generalized SAD with venlafaxine extended release. Abstract presented at: the annual meeting of the American Psychiatric Association. May 17-22, 2003; San Francisco, Calif."},{"key":"S1092852900022392_ref038","doi-asserted-by":"publisher","DOI":"10.3109\/15622970209150621"},{"key":"S1092852900022392_ref020","first-page":"47","article-title":"Pharmacotherapy of social anxiety disorder","volume":"59","author":"Davidson","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"S1092852900022392_ref016","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.2.275"},{"key":"S1092852900022392_ref021","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1999.tb10845.x"},{"key":"S1092852900022392_ref068","doi-asserted-by":"publisher","DOI":"10.1037\/0022-006X.71.6.1058"},{"key":"S1092852900022392_ref040","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199709000-00001"},{"key":"S1092852900022392_ref011","first-page":"167","article-title":"Double-blind placebo-controlled study of bromazepam in social phobia. Serie psicofarmacologia-59","volume":"46","author":"Verisani","year":"1997","journal-title":"J Bass Psiquitr"},{"key":"S1092852900022392_ref053","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-7967(98)00175-2"},{"key":"S1092852900022392_ref036","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-6185(02)00134-2"},{"key":"S1092852900022392_ref030","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950120047008"},{"key":"S1092852900022392_ref066","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.179.1.23"},{"key":"S1092852900022392_ref010","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199312000-00008"},{"key":"S1092852900022392_ref006","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.12.1133"},{"key":"S1092852900022392_ref054","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199907000-00006"},{"key":"S1092852900022392_ref091","doi-asserted-by":"crossref","first-page":"38S","DOI":"10.1177\/070674372001460101004","article-title":"Clinical guidelines for the treatment of depressive disorders IV. Medication and other biological treatments","volume":"46","author":"Kennedy","year":"2001","journal-title":"Can J Psychiatry"},{"key":"S1092852900022392_ref012","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244762"},{"key":"S1092852900022392_ref039","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-198808000-00008"},{"key":"S1092852900022392_ref001","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"1994"},{"key":"S1092852900022392_ref061","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-2406.2003.00058.x"},{"key":"S1092852900022392_ref089","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6394(1998)7:3<126::AID-DA5>3.0.CO;2-9"},{"key":"S1092852900022392_ref008","doi-asserted-by":"publisher","DOI":"10.1016\/0924-977X(92)90032-4"},{"key":"S1092852900022392_ref043","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(96)00013-4"},{"key":"S1092852900022392_ref026","first-page":"322","article-title":"Functional impairment in social phobia","volume":"55","author":"Schneier","year":"1994","journal-title":"J Clin Psychiatry"},{"key":"S1092852900022392_ref045","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v63n0211"},{"key":"S1092852900022392_ref083","unstructured":"Denys D , Van Megen H , Westenberg H . A double-blind, placebo-controlled study of quetiapine addition in treatment refractory patients with OCD. Poster presented at: annual meeting of the American Psychiatric Association. May 17-22, 2003; San Francisco, Calif."},{"key":"S1092852900022392_ref050","doi-asserted-by":"publisher","DOI":"10.1016\/0005-7967(96)00028-9"},{"key":"S1092852900022392_ref017","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.179.1.23"},{"key":"S1092852900022392_ref079","first-page":"169","article-title":"Valproic acid for the treatment of social anxiety disorder","volume":"18","author":"Kinrys","year":"2003","journal-title":"Int Clin Psychopharmacol"},{"key":"S1092852900022392_ref080","first-page":"244","article-title":"Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder","volume":"65","author":"Seedat","year":"2004","journal-title":"J Clin Psychiatry"},{"key":"S1092852900022392_ref029","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(00)00323-2"},{"key":"S1092852900022392_ref002","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950010008002"},{"key":"S1092852900022392_ref003","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.10.1558"},{"key":"S1092852900022392_ref005","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.49.4.290"},{"key":"S1092852900022392_ref081","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1176\/ajp.152.12.1812","article-title":"Lack of efficacy of clozapine monotherapy in refractory obsessive-compulsive disorder","volume":"152","author":"McDougle","year":"1995","journal-title":"Am J Psychiatry"},{"key":"S1092852900022392_ref042","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-6185(00)00027-X"},{"key":"S1092852900022392_ref031","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-9338(00)00211-X"},{"key":"S1092852900022392_ref009","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199606003-00014"},{"key":"S1092852900022392_ref015","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1176\/ajp.152.9.1368","article-title":"Sertraline for social phobia: a double-blind, placebo controlled crossover study","volume":"152","author":"Katzelnick","year":"1995","journal-title":"Am J Psychiatry"},{"key":"S1092852900022392_ref018","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.8.708"},{"key":"S1092852900022392_ref019","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.175.2.120"},{"key":"S1092852900022392_ref024","unstructured":"Feltner DE , Pollack MH , Davidson JR , et al. A placebo-controlled study of pregabalin in the treatment of social phobia. Poster presented at: annual meeting of the Anxiety Disorders Association of America. March 23-26, 2000; Washington, DC."},{"key":"S1092852900022392_ref025","doi-asserted-by":"publisher","DOI":"10.1002\/da.10096"},{"key":"S1092852900022392_ref027","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-6185(02)00228-1"},{"key":"S1092852900022392_ref058","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.10.1725"},{"key":"S1092852900022392_ref033","first-page":"54","article-title":"Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety","volume":"59","author":"Ballenger","year":"1998","journal-title":"J Clin Psychiatry"}],"container-title":["CNS Spectrums"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1092852900022392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T10:57:36Z","timestamp":1749034656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1092852900022392\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10]]},"references-count":91,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2004,10]]}},"alternative-id":["S1092852900022392"],"URL":"https:\/\/doi.org\/10.1017\/s1092852900022392","relation":{},"ISSN":["1092-8529","2165-6509"],"issn-type":[{"value":"1092-8529","type":"print"},{"value":"2165-6509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10]]}}}