{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:26:50Z","timestamp":1773325610158,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,3,24]],"date-time":"2006-03-24T00:00:00Z","timestamp":1143158400000},"content-version":"vor","delay-in-days":600,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Methods Psych Res"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Unipolar major depression is often a chronic disease that may require lifelong prophylaxis. Recovery from an acute episode is followed by 4\u20106 months of relapse prevention. After that, long\u2010term maintenance treatment is administered to avoid recurrence.<\/jats:p><jats:p>We present the rationale and design of an ongoing double\u2010blind, randomized, placebo\u2010controlled trial investigating the efficacy of Hypericum extract WS<jats:sup>\u00ae<\/jats:sup> 5570 in relapse prevention in recurrent unipolar depression. An estimated sample of 425 adults with recurrent, mild to moderate major depression (ICD\u201010 and DSM\u2010IV criteria), \u22653 previous episodes (last 5 years) and a total score \u226520 points on the 17\u2010item Hamilton Rating Scale for Depression (HAMD) will be included. After a one\u2010week wash out patients receive 3 \u00d7 300 mg\/day WS<jats:sup>\u00ae<\/jats:sup> 5570 single\u2010blind for 6 weeks. Responders are randomized to 26 weeks of double\u2010blind continuation treatment with 3 \u00d7 300 mg\/day WS<jats:sup>\u00ae<\/jats:sup> 5570 or placebo. Patients completing continuation treatment without relapse enter 52 weeks of double\u2010blind maintenance treatment, where those treated with WS<jats:sup>\u00ae<\/jats:sup> 5570 are re\u2010randomized to 3 \u00d7 300 mg\/day WS<jats:sup>\u00ae<\/jats:sup> 5570 or placebo. The primary outcome measure is the time to relapse during continuation treatment (HAMD \u226516, clinical diagnosis of depression, or premature treatment termination for inefficacy).<\/jats:p><jats:p>Hypericum extract, with its favourable tolerability profile, could be an interesting option for long\u2010term prophylaxis. The trial was designed according to current consensus and guidance. Notably, it includes long\u2010term prophylactic treatment with the same drug and the same therapeutic dose applied during acute treatment, uses well\u2010defined outcome measures and provides a clear distinction between relapse and recurrence. Copyright \u00a9 2004 Whurr Publishers Ltd.<\/jats:p>","DOI":"10.1002\/mpr.173","type":"journal-article","created":{"date-parts":[[2006,3,24]],"date-time":"2006-03-24T14:50:15Z","timestamp":1143211815000},"page":"176-183","source":"Crossref","is-referenced-by-count":8,"title":["Continuation and long\u2010term maintenance treatment with Hypericum extract WS<sup>\u00ae<\/sup> 5570 after successful acute treatment of mild to moderate depression \u2013 rationale and study design"],"prefix":"10.1002","volume":"13","author":[{"given":"S.","family":"Kasper","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Dienel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kieser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3,24]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1014287"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4679(198411)40:6<1365::AID-JCLP2270400615>3.0.CO;2-D"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/10673229609030517"},{"key":"e_1_2_1_5_1","first-page":"33","article-title":"The booming US botanical market","volume":"44","author":"Brevoort P","year":"1998","journal-title":"Herbalgram"},{"key":"e_1_2_1_6_1","volume-title":"Guidelines for the clinical evaluation of antidepressant drugs. Report No. HEW (FDA) 77\u20103042","author":"Center for Drug Evaluation and Research","year":"1978"},{"key":"e_1_2_1_7_1","volume-title":"Note for Guidance on the Clinical Investigation of Medical Products in the Treatment of Depression. Report No.: CPMP\/EWP\/518\/97","author":"Committee for Proprietary Medical Products","year":"2002"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.150.5.720"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.313.7052.241"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.11.1519"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050519"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780010204"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12599-8"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780110107"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8260.1967.tb00530.x"},{"key":"e_1_2_1_16_1","first-page":"637","article-title":"Herbal medicine takes root in Germany","volume":"158","author":"Harrison P","year":"1998","journal-title":"Canadian Medical Association Journal"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1001\/jama.1997.03540280071036","article-title":"The National Depressive and Manic\u2010Depressive Association consensus statement on the undertreatment of depression","volume":"277","author":"Hirschfeld RM","year":"1997","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780110810"},{"key":"e_1_2_1_19_1","volume-title":"ICH topic E6 \u2013 Good clinical practice \u2013 consolidated guidance","author":"International Conference on Harmonization","year":"1996"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-14280"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1203-2"},{"key":"e_1_2_1_22_1","first-page":"577","article-title":"Langzeitbehandlung affektiver St\u00f6rungen","volume":"65","author":"Kasper S","year":"1994","journal-title":"Nervenarzt"},{"key":"e_1_2_1_23_1","first-page":"59","article-title":"Diagnostik und Therapie der Depression \u2013 Konsensus\u2010Statement","volume":"11","author":"Kasper S","year":"1997","journal-title":"Neuropsychiatrie"},{"issue":"17","key":"e_1_2_1_24_1","first-page":"41","article-title":"The long\u2010term treatment of depression","volume":"60","author":"Keller MB","year":"1999","journal-title":"Journal of Clinical Psychiatry"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(98)00110-3"},{"issue":"6","key":"e_1_2_1_26_1","first-page":"22","article-title":"Anxiety symptom relief in depression treatment outcomes","volume":"56","author":"Keller MB","year":"1995","journal-title":"Journal of Clinical Psychiatry"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950010008002"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199909000-00002"},{"issue":"12","key":"e_1_2_1_29_1","first-page":"17","article-title":"Lessons to be learned from long\u2010term treatment of affective disorders: potential utility in panic disorder","volume":"52","author":"Kupfer DJ","year":"1991","journal-title":"Journal of Clinical Psychiatry"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820100013002"},{"issue":"1","key":"e_1_2_1_31_1","first-page":"545","article-title":"St John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy","volume":"31","author":"Laakmann G","year":"1998","journal-title":"Pharmacopsychiatry"},{"key":"e_1_2_1_32_1","first-page":"211","article-title":"Recurrence after recovery in unipolar MDD: an observational follow\u2010up study of clinical predictors and somatic treatment as a mediating factor","volume":"4","author":"Lavori PW","year":"1994","journal-title":"International Journal of Methods in Psychiatric Research"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.8.1361"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199701000-00003"},{"key":"e_1_2_1_35_1","article-title":"St John's wort for depression","author":"Linde K","year":"2000","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.12.1128"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820100005001"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1017176"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/026988118900300201"},{"issue":"26","key":"e_1_2_1_40_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1192\/S0007125000293264","article-title":"Long\u2010term treatment of depression","author":"Montgomery SA","year":"1994","journal-title":"British Journal of Psychiatry"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(98)00049-2"},{"issue":"6","key":"e_1_2_1_42_1","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1097\/00004850-199807006-00005","article-title":"Depression: a long\u2010term illness and its treatment","volume":"13","author":"Montgomery SA","year":"1998","journal-title":"International Clinical Psychopharmacology"},{"key":"e_1_2_1_43_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/00004850-199803000-00002","article-title":"Mirtazapine versus amitriptyline in the long\u2010term treatment of depression: a double\u2010blind placebo\u2010controlled study","volume":"13","author":"Montgomery SA","year":"1998","journal-title":"Int Clin Psychopharmacol"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979521"},{"key":"e_1_2_1_45_1","first-page":"12\u20101","volume-title":"Translator and Editor Manual for the EDCEU Assessment Battery","author":"National Institute of Mental Health","year":"1976"},{"issue":"16","key":"e_1_2_1_46_1","first-page":"5","article-title":"Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment\u2010resistant depression","volume":"62","author":"Nierenberg AA","year":"2001","journal-title":"Journal of Clinical Psychiatry"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.143.1.18"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.155.9.1247"},{"key":"e_1_2_1_49_1","first-page":"119","article-title":"Johanniskrautextrakt WS 5572 bei leichten bis mittelschweren Depressionen. Wirksamkeit und Vertr\u00e4glichkeit von 600 und 1200 mg Wirkstoff t\u00e4glich","volume":"119","author":"Rychlik R","year":"2001","journal-title":"Fortschritte der Medizin"},{"key":"e_1_2_1_50_1","first-page":"152","article-title":"Incidence and clinical relevance of the interactions and side effects of Hypericum preparations","volume":"8","author":"Schulz V","year":"2001","journal-title":"Phytomedicine"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-199809060-00002"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001504-200201000-00011"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/089198879400700110"}],"container-title":["International Journal of Methods in Psychiatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmpr.173","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mpr.173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T17:18:29Z","timestamp":1700241509000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mpr.173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1002\/mpr.173"],"URL":"https:\/\/doi.org\/10.1002\/mpr.173","archive":["Portico"],"relation":{},"ISSN":["1049-8931","1557-0657"],"issn-type":[{"value":"1049-8931","type":"print"},{"value":"1557-0657","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]}}}