{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:57:27Z","timestamp":1777417047031,"version":"3.51.4"},"reference-count":20,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2000,2,1]],"date-time":"2000-02-01T00:00:00Z","timestamp":949363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE:<\/jats:title>\n                    <jats:p>To compare the relative efficacy and safety of lesopitron 40\u201380 mg\/d versus lorazepam 2\u20134 mg\/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DESIGN:<\/jats:title>\n                    <jats:p>Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SETTING:<\/jats:title>\n                    <jats:p>Outpatient clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS:<\/jats:title>\n                    <jats:p>One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.19041","type":"journal-article","created":{"date-parts":[[2003,6,3]],"date-time":"2003-06-03T16:37:26Z","timestamp":1054658246000},"page":"147-153","source":"Crossref","is-referenced-by-count":18,"title":["Efficacy and Safety of Lesopitron in Outpatients with Generalized Anxiety Disorder"],"prefix":"10.1177","volume":"34","author":[{"given":"Anna","family":"Fresquet","sequence":"first","affiliation":[{"name":"Anna Fresquet MD MS(Pharm), Clinical Research, Laboratorios Dr. Esteve, S.A., Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariano","family":"Sust","sequence":"additional","affiliation":[{"name":"Mariano Sust MD MS, Biostatistics, Clinical Research, Laboratorios Dr. Esteve, S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Lloret","sequence":"additional","affiliation":[{"name":"Antonio Lloret BSN, Clinical Research Associate, Laboratorios Dr. Esteve, S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F","family":"Murphy","sequence":"additional","affiliation":[{"name":"Michael F Murphy MD PhD, Vice President, Scientific Affairs, Worldwide Clinical Trials, Chadds Ford, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick J","family":"Carter","sequence":"additional","affiliation":[{"name":"Frederick J Carter MS, Manager of Statistical Computing, Solvay Pharmaceuticals, Marietta, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giedra M","family":"Campbell","sequence":"additional","affiliation":[{"name":"Giedra M Campbell MA, Manager, Medical Writing, Worldwide Clinical Trials, Kennesaw, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaston","family":"Marion-Landais","sequence":"additional","affiliation":[{"name":"Gaston Marion-Landais MD, Medical Monitor, Worldwide Clinical Trials, Kennesaw"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2000,2,1]]},"reference":[{"key":"bibr1-aph.19041","doi-asserted-by":"publisher","DOI":"10.1358\/dof.1994.019.07.254340"},{"key":"bibr2-aph.19041","unstructured":"Fisas MA, Colombo A, Gutierrez B, Colombo M, Farre AF. Activity of a series of non-benzodiazepine anxiolytic agents in a battery of conventional anxiety\/conflict tests. In: Proceedings of the IV Reuniao conjunta das Sociedades Portuguesa e Espanhola de Farmacologia, Lisboa, Portugal, February 28\u2013March 2, 1991."},{"key":"bibr3-aph.19041","unstructured":"Farre JA, Colombo A, Fisas MA, Gutierrez B, Fort M, Martinez L,  Pharmacological study of a series of non-benzodiazepine anxiolytic agents. In: Proceedings of the IV Reuniao conjunta das Sociedades Portuguesa e Espanhola de Farmacologia, Lisboa, Portugal, February 28\u2013 March 2, 1991."},{"key":"bibr4-aph.19041","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-199204001-00067"},{"key":"bibr5-aph.19041","first-page":"90","volume":"262","author":"Costall B","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"bibr6-aph.19041","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-199204001-00056"},{"key":"bibr7-aph.19041","unstructured":"Serafini MT, Puig S, Garcia G, Farran R, Garcia A, Martinez L. In vitro metabolism of lesopitron by liver microsomes from different animal species (abstract). In: Proceedings of the European Conference on Specificity and Variability in Drug Metabolism, Besan\u00e7on, France, May 1995."},{"key":"bibr8-aph.19041","volume-title":"Data on file"},{"key":"bibr9-aph.19041","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199612000-00009"},{"key":"bibr10-aph.19041","volume-title":"Data on file."},{"key":"bibr11-aph.19041","volume-title":"Data on file"},{"key":"bibr12-aph.19041","unstructured":"American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994: 432\u20136."},{"key":"bibr13-aph.19041","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(94)90040-X"},{"key":"bibr14-aph.19041","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03470010097038"},{"key":"bibr15-aph.19041","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(94)90134-1"},{"key":"bibr16-aph.19041","doi-asserted-by":"publisher","DOI":"10.1016\/0010-440X(87)90013-7"},{"key":"bibr17-aph.19041","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-198710000-00004"},{"key":"bibr18-aph.19041","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(96)00077-8"},{"key":"bibr19-aph.19041","first-page":"117","volume":"47","author":"Mavissakalian M","year":"1986","journal-title":"J Clin Psychiatry"},{"key":"bibr20-aph.19041","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199606000-00009"}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.19041","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.19041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:02:59Z","timestamp":1777374179000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1345\/aph.19041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,2]]}},"alternative-id":["10.1345\/aph.19041"],"URL":"https:\/\/doi.org\/10.1345\/aph.19041","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,2]]}}}