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Pharmacopsychiatry 2006; 39(6): 213-219
DOI: 10.1055/s-2006-951388
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Comparison of Hypericum Extract WS® 5570 and Paroxetine in Ongoing Treatment after Recovery from an Episode of Moderate to Severe Depression: Results from a Randomized Multicenter Study

I. G. Anghelescu 1 , R. Kohnen 2 , A. Szegedi 1 , S. Klement 3 , M. Kieser 3
  • 1Department of Psychiatry and Psychotherapy, Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
  • 2IMEREM, Institute for Medical Research Management and Biometrics, Nürnberg, Germany
  • 3Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany
Further Information

Publication History

Received 22. 3. 2006 Revised 20. 7. 2006

Accepted 24. 7. 2006

Publication Date:
23 November 2006 (online)

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Objective: To test and compare the efficacy and safety of Hypericum extract WS® 5570 to paroxetine, a potent SSRI, in patients suffering from moderate or severe depression according to DSM-IV criteria. Methods: In a multicenter, randomized, double-blind phase III study, the changes in moderate to severe major depression DSM-IV; 17-item Hamilton Depression Rating Scale (HAM-D total ≥22) after an acute treatment with Hypericum extract WS® 5570 or paroxetine were analyzed in a 16-week continuation phase for relapse prevention. Patients with a HAM-D total score decrease of ≥50% during the 6 weeks of acute treatment were asked to continue the treatment for another 4 months. One-hundred and thirty-three adult out-patients who received maintenance doses of 900 (n=33) or 1800 mg/d (n=38) of WS® 5570 and 20 (n=28) or 40 mg/d (n=34) of paroxetine, respectively, were included. The relevant dosage was already fixed during the acute treatment. Results: Between baseline of the acute phase and end of continuation treatment the HAM-D total score decreased from 25.3±2.5 (mean±SD) to 4.3±6.2 points for WS® 5570 and from 25.3±2.6 to 5.2±5.5 points for paroxetine (p=0.49, two-sided t-test; median relative decrease: 92.0 and 85.5%, respectively). During maintenance treatment alone (day 154 - day 42), 61.6% of the patients randomized to WS® 5570 and 54.6% treated with paroxetine showed an additional reduction (p=0.59) with respect to the HAM-D total score. Remission (HAM-D endpoint total score below 8) occurred in 81.6% (31 patients) of the patients for WS® 5570 and in 71.4% (30 patients) for paroxetine (p=0.29). Three patients in the WS® 5570 group and 2 patients in the paroxetine group showed a HAM-D increase >5 points during continuation treatment. In the continuation phase there were 0.006 adverse events per day of exposure for WS® 5570 and 0.007 events for paroxetine. Conclusion: This study showed that WS® 5570 and paroxetine were similarly effective in preventing relapse in a continuation treatment after recovery from an episode of moderate to severe depression and point therefore to an important alternative treatment option for long-term relapse-prevention.

References

  • 1 American Psychiatric Association . DSM - Diagnostic and Statistical Manual of Mental Disorders.  , [electronic mail system] 2000; 
    Google Scholar
  • 2 Baldwin DS, Hawley CJ, Mellors K. CN104-070 Study Group . A randomized, double-blind controlled comparison of nefazodone and paroxetine in the treatment of depression: safety, tolerability and efficacy in continuation phase treatment.  J Psychopharmacol. 2001;  15 161-165
    PubMedGoogle Scholar
  • 3 Beck AT, Steer RA. Internal consistencies of the original and revised Beck Depression Inventory.  J Clin Psychol. 1984;  40 1365-1367
    PubMedGoogle Scholar
  • 4 Bourin M, Chue P, Guillon Y. Paroxetine: a review.  CNS Drug Rev. 2001;  7 25-47
    PubMedGoogle Scholar
  • 5 Bump GM, Mulsant BH, Pollock BG, Mazumdar S, Begley AE, Dew MA, Reynolds CF3. Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly.  Depress Anxiety. 2001;  13 38-44
    CrossrefPubMedGoogle Scholar
  • 6 Chatterjee SS, Nöldner M, Koch E, Erdelmeier CAJ. Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility.  Pharmacopsychiatry. 1998;  31 ((Suppl 1)) 7-15
    PubMedGoogle Scholar
  • 7 Dunner DL, Kumar R. Paroxetine: a review of clinical experience.  Pharmacopsychiatry. 1998;  31 89-101
    PubMedGoogle Scholar
  • 8 Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.).  Eur J Clin Pharmacol. 1998;  54 589-594
    CrossrefPubMedGoogle Scholar
  • 9 Gastpar M, Singer A, Zeller K. Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline.  Pharmacopsychiatry. 2005;  38 78-86
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.  Pharmacopsychiatry. 2006;  39 66-75
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Hamilton M. Development of a rating scale for primary depressive illness.  Br J Soc Clin Psychol. 1967;  6 278-296
    PubMedGoogle Scholar
  • 12 Harrer G, Hübner WD, Podzuweit H. Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study.  J Geriatr Psychiatry Neurol. 1994;  7 S24-S28
    PubMedGoogle Scholar
  • 13 Harrer G, Schmidt U, Kuhn U, Biller A. quivalenzvergleich Johanniskraut LoHyp-57 versus Fluoxetin.  Arzneimittelforschung. 1998;  49 3-10
    PubMedGoogle Scholar
  • 14 Hindmarch I. The behavioural toxicity of antidepressants: effects on cognition and sexual function.  Int Clin Psychopharmacol. 1998;  13 S5-S8
    PubMedGoogle Scholar
  • 15 Hirschfeld RM, Keller MB, Panico S, Arons BS, Barlow D, Davidoff J, Endicott J, Froom J, Goldstein M, Gorman JM. et al . The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression.  JAMA. 1997;  277 330-340
    PubMedGoogle Scholar
  • 16 Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St. John's Wort extract WS®5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial.  BMC Medicine. 2006;  4 14 DOI: doi:10.1186/1741-7015-4-14
    CrossrefPubMedGoogle Scholar
  • 17 Kasper S, Dienel A. Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials.  Psychopharmacology. 2002;  164 301-308
    CrossrefPubMedGoogle Scholar
  • 18 Kasper S, Dienel A, Kieser M. Hypericum extract WS 5570 has a beneficial effect in continuation treatment of recurrent depression.  Pharmacopsychiatry. 2005;  38 236 , Ref Type: Abstract
    PubMedGoogle Scholar
  • 19 Kasper S, Zapotoczky HG, Stuppäck C, König P, Wuschitz A. Diagnostik und Therapie der Depression - Konsensus statement.  Neuropsychiatrie. 1997;  11 59-67
    PubMedGoogle Scholar
  • 20 Keller MB, Boland RJ. Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression.  Biol Psychiatry. 1998;  44 348-360
    CrossrefPubMedGoogle Scholar
  • 21 Keller MB, Hanks DL. Anxiety symptom relief in depression treatment outcomes.  J Clin Psychiatry. 1995;  56 ((Suppl 6)) 22-29
    PubMedGoogle Scholar
  • 22 Kim HL, Streltzer J, Goebert D. St. John's wort for depression: a meta-analysis of well-defined clinical trials.  J Nerv Ment Dis. 1999;  187 532-539
    CrossrefPubMedGoogle Scholar
  • 23 Kupfer DJ. Lessons to be learned from long-term treatment of affective disorders: potential utility in panic disorder.  J Clin Psychiatry. 1991;  52 ((Suppl)) 12-16
    PubMedGoogle Scholar
  • 24 Kupfer DJ, Frank E, Perel JM, Cornes C, Mallinger AG, Thase ME, McEachran AB, Grochochinski VJ. Five-year outcome for maintenance therapies in recurrent depression.  Arch Gen Psychiatry. 1992;  49 769-773
    PubMedGoogle Scholar
  • 25 Laakmann G, Schüle C, Baghai T, Kieser M. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy.  Pharmacopsychiatry. 1998;  31 ((Suppl 1)) 54-59
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Lauritzen L, Odgaard K, Clemmesen L, Lunde M, Ohrstrom J, Black C, Bech P. Relapse prevention by means of paroxetine in ECT-treated patients with major depression: a comparison with imipramine and placebo in medium-term continuation therapy.  Acta Psychiatr Scand. 1996;  94 241-251
    CrossrefPubMedGoogle Scholar
  • 27 Lecrubier Y. Is depression under-recognised and undertreated?.  Int Clin Psychopharmacol. 1998;  13 ((Suppl 5)) S3-S6
    PubMedGoogle Scholar
  • 28 Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial.  Am J Psychiatry. 2002;  159 1361-1369
    CrossrefPubMedGoogle Scholar
  • 29 Linde K, Berner M, Egger M, Mulrow CD. St John's wort for depression: meta-analysis of randomised controlled trials.  Br J Psychiatry. 2005;  186 99-107
    PubMedGoogle Scholar
  • 30 Melfi CA, Chawla AJ, Croghan TW, Hanna MP, Kennedy S, Sredl K. The effects of adherence to antidepressant treatment guidelines on relapse and recurrence of depression.  Arch Gen Psychiatry. 1998;  55 1128-1132
    CrossrefPubMedGoogle Scholar
  • 31 Montgomery SA. Long-term treatment of depression.  Br J Psychiatry Suppl. 1994;  31-36
    PubMedGoogle Scholar
  • 32 Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change.  Br J Psychiatry. 1979;  134 382-389
    CrossrefPubMedGoogle Scholar
  • 33 Montgomery SA, Kasper S. Depression: a long-term illness and its treatment.  Int Clin Psychopharmacol. 1998;  13 ((Suppl 6)) S23-S26
    PubMedGoogle Scholar
  • 34 Müller WE, Singer A, Wonnemann M. Hyperforin - antidepressant activity by a novel mechanism of action.  Pharmacopsychiatry. 2001;  34 ((Suppl 1)) S98-S102
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 National Institute of Mental Health . CGI: Clinical Global Impressions. Guy, W. and Bonato, R. R. Manual for the ECDEU Assessment Battery 2nd rev.  , 12.1-12.6. 1976. Chevy Chase, MD. Ref Type: Serial (Book, Monograph)
    Google Scholar
  • 36 Philipp M, Kohnen R, Hiller K-O. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.  BMJ. 1999;  319 1534-1539
    PubMedGoogle Scholar
  • 37 Preskorn SH. Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine.  J Clin Psychiatry. 1995;  56 ((Suppl 6)) 12-21
    PubMedGoogle Scholar
  • 38 Prien RF, Kupfer DJ. Continuation drug therapy for major depressive episodes: how long should it be maintained?.  Am J Psychiatry. 1986;  143 18-23
    PubMedGoogle Scholar
  • 39 Settle Jr EC. Antidepressant drugs: disturbing and potentially dangerous adverse effects.  J Clin Psychiatry. 1998;  59 ((Suppl 16)) 25-30
    PubMedGoogle Scholar
  • 40 Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.  BMJ. 2005;  330 503-506
    CrossrefPubMedGoogle Scholar
  • 41 Traynor K. Severe depression does not respond to St. John's wort, study says.  Am J Health Syst Pharm. 2001;  58 954-956
    PubMedGoogle Scholar
  • 42 Volz H-P. Controlled clinical trials of hypericum extracts in depressed patients - on overview.  Pharmacopsychiatry. 1997;  30 ((Suppl 2)) 72-76
    PubMedGoogle Scholar
  • 43 Vorbach EU, Arnoldt KH, Hübner WD. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10.  Pharmacopsychiatry 30 81-85 Pharmacopsychiatry. 1997;  30 ((Suppl 2)) 81-85
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Vorbach EU, Hübner WD, Arnoldt KH. Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double-blind study with 135 outpatients.  J Geriatr Psychiatry Neurol. 1994;  7 ((Suppl 1)) S19-S23
    PubMedGoogle Scholar
  • 45 Welzel D, Kohnen R, Krüger HP, Vollrath M, Drechsler S. Farbskalen zur Messung von Befindlichkeit und Lebensqualität. In: Möller HJ, Engel RR, Hoff P, editors. Befunderhebung in der Psychiatrie: Lebensqualität, Negativsymptomatik und andere aktuelle Entwicklungen. Berlin: Springer 1996: 133-152
    Google Scholar
  • 46 Wheatley D. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients-a controlled 6-week clinical trial.  Pharmacopsychiatry. 1997;  30 ((Suppl 2)) 77-80
    PubMedGoogle Scholar
  • 47 Wheatley D. Hypericum extract - potential in the treatment of depression.  CNS Drugs. 1998;  9 431-440
    PubMedGoogle Scholar
  • 48 Williams Jr JW, Mulrow CD, Chiquette E, Hitchcock P, Aguilar C, Cornell J. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.  Ann Int Med. 2000;  132 743-756
    PubMedGoogle Scholar
  • 49 Winkler D, Tauscher J, Kasper S. Maintenance treatment in depression: the role of pharmacological and psychological treatment.  Curr Opin Psych. 2002;  15 63-68
    PubMedGoogle Scholar

Correspondence

Dr. Stephan Klement

Dr. Willmar Schwabe Pharmaceuticals

P. O. Box 410925

76209 Karlsruhe

Germany

Phone: +49/721/40 05 51 4

Fax: +49/721/40 05 85 14

Email: stephan.klement@schwabe.de