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Pharmacopsychiatry 2006; 39(2): 66-75
DOI: 10.1055/s-2006-931544
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

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

M. Gastpar1 , A. Singer2 , K. Zeller3
  • 1General Psychiatric Hospital, Department of Psychiatry and Psychotherapy, University of Essen, Essen, Germany
  • 2EPA Euro Pharma Auftragsforschung GmbH, Kronberg, Germany
  • 3Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
Further Information

Publication History

Received: 5.5.2005 Revised: 14.12.2005

Accepted: 21.12.2005

Publication Date:
23 March 2006 (online)

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Objective: The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen’s Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo. Methods: Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs. Results: From almost identical baseline values of 21.9 ± 1.2 points (hypericum extract), 21.8 ± 1.2 points (citalopram) and 22.0 ± 1.2 points (placebo), the HAMD score was reduced to 10.3 ± 6.4 (hypericum extract), 10.3 ± 6.4 (citalopram) and 13.0 ± 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with ”certain”, ”probable” or ”possible” relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as ”good” or ”very good”. Conclusion: The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.

References

  • 1 Bezchlibnyk-Butler K, Aleksic I, Kennedy S H. Citalopram - a review of pharmacological and clinical effects.  J Psychiatry Neurosc. 2000;  25 241-254
    PubMedSearch in Google Scholar
  • 2 Bracher A. Johanniskraut 1 × täglich: Wirkung klinisch belegt/HYP611-Studie bestätigt Wirksamkeit.  Supplement to Ärztliche Praxis. 2001;  51 1-4
    PubMedSearch in Google Scholar
  • 3 Brenner R, Azbel V. Comparison of an extract of hypericum (LI 160) and Sertraline in the treatment of depression: a double-blind, randomised pilot study.  Clin Ther. 2000;  22 411-419
    CrossrefPubMedSearch in Google Scholar
  • 4 Brockmöller J, Reum T, Bauer S, Kerb R, Hübner W -D, Roots I. Hypericin and Pseudohypericin: Pharmacokinetics and Effects on Photosensitivity in Humans.  Pharmacopsychiatry. 1997;  30 8Suppl.) 94-101
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 DSM -I V. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. The American Psychiatric Association Washington; 1994: 339-345
    Search in Google Scholar
  • 6 ESCOP . Hyperici herba St. John’s wort. ESCOP Monography 1996
    Search in Google Scholar
  • 7 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
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Guy W, ed. ECDEU Assessment Manual for Psychopharmacology. Rockville, Md; National Institutes of Mental Health 1976 Publication ADM 76-338
    Search in Google Scholar
  • 9 Hamilton M. A rating scale for depression.  J Neurol Neurosurg Psychiatry. 1960;  23 56-62
    CrossrefPubMedSearch in Google Scholar
  • 10 Hovorka J, Herman E, Nemcova I I. Treatment of Interictal Depression with Citalopram in Patients with Epilepsy.  Epilepsy Behav. 2001;  6 444-447
    PubMedSearch in Google Scholar
  • 11 Hypericum Depression Trial Study G roup. Effect of Hypericum perforatum (St. John’s Wort) in major depressive disorders.  JAMA. 2002;  14 1807-1814
    PubMedSearch in Google Scholar
  • 12 IC D -10. Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme 10 Revision (in German). Deutsche Institut für medizinische Dokumentation und Information (DIMDI). Published on behalf of Federal Ministry of Health. Version 1.0 Updated August 1994
    Search in Google Scholar
  • 13 Kasper S. Hypericum perforatum - a review of clinical studies.  Pharmacopsychiatry. 2001;  34 (Suppl. 1) 51-55
    PubMedSearch in Google Scholar
  • 14 Keller M B. Citalopram therapy for depression: a review of 10 years of European experience and data from U.S. clinical trials.  J Clin Psychiatry. 2000;  61 896-908
    PubMedSearch in Google Scholar
  • 15 Kerb R, Brockmoller J, Staffeldt B, Ploch M, Roots I. Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.  Antimicrob Agents Chemother. 1996ep;  40 2087-2093
    PubMedSearch in Google Scholar
  • 16 Kessler R C, McGonagle K A, Zhao S, Nelson C B, Hughes M, Eshleman S. et al . Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey.  Arch Gen Psychiatry. 1994;  51 8-19
    PubMedSearch in Google Scholar
  • 17 Khan A, Detke M, Khan S R, Mallinckrodt C. Placebo response and antidepressant clinical trial outcome.  J Nerv Ment Dis. 2003;  191 211-218
    CrossrefPubMedSearch in Google Scholar
  • 18 Kommission E. Monographie Hyperici herba (Johanniskraut) (in German). Bundesanzeiger 228 05.12.1984
    Search in Google Scholar
  • 19 Lepine J P, Gastpar M, Mendlewicz J, Tylee A. Depression in the community: the first pan-European study DEPRES (Depression Research in European Society).  Int Clin Psychopharmacol. 1997;  12 19-29
    PubMedSearch in Google Scholar
  • 20 Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D. St John’s wort for depression (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software - an overview and meta-analysis of randomised clinical trials.  BMJ. 1996;  313 253-258
    PubMedSearch in Google Scholar
  • 21 Markowitz J S, Donovan J L, DeVane C L, Taylor R M, Ruan Y, Wang J -S. et al . Effect of St. John’s Wort on drug metabolism by induction of cytochrome P450 3A4 Enzyme.  JAMA. 2003;  290 1500-1504
    CrossrefPubMedSearch in Google Scholar
  • 22 Möller H J. et al . Psychiatrie. Hippokrates Verlag Stuttgart; 1996
    Search in Google Scholar
  • 23 Montejo Iglesias M L, Oca Bravo L, Soler Roibal A. Factors associated with antidepressive placebo response: a review.  Actas Esp Psiquiatr . 2002;  30 246-252
    PubMedSearch in Google Scholar
  • 24 Müller W E, Rolli M, Schäfer C, Hafner U. Effects of Hypericum Extract (LI160) in Biochemical Models of Antidepressant Activity.  Pharmacopsychiatry. 1997;  30 102-107
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Nemeroff C B. Overview of the safety of citalopram.  Psychopharmacol Bull. 2003;  37 96-121
    PubMedSearch in Google Scholar
  • 26 Parker N G, Brown C S. Citalopram in the treatment of depression.  Ann Pharmacother. 2000;  34 761-771
    PubMedSearch in Google Scholar
  • 27 Philipp M, Kohen 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
    PubMedSearch in Google Scholar
  • 28 Pollock B G. Citalopram: a comprehensive review.  Expert Opin Pharmacother. 2001;  2 681-698
    PubMedSearch in Google Scholar
  • 29 Rychlik R, Siedentop H, von den Driesch V, Kasper S. St. John’s wort extract WS 5572 in minor to moderately severe depression. Effectiveness and tolerance of 600 and 1200 mg active ingredient daily.  Fortschr Med Orig. 2001;  119 119-128
    PubMedSearch in Google Scholar
  • 30 Schrader E. Equivalence of St John’s wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.  Int Clin Psychopharmacol. 2000;  15 61-68
    PubMedSearch in Google Scholar
  • 31 Schulz H -U, Schürer M, Bässler D, Weiser D. Investigation of the Bioavailability of Hypericin, Pseudohypericin, Hyperforin and the Flavonoids Quercetin and Isorhamnetin Following Single and Multiple Oral Dosing of a Hypericum Extract containing Tablet.  Drug Res. 2005;  55 15-22
    PubMedSearch in Google Scholar
  • 32 Schulz H -U, Schürer M, Bässler D, Weiser D. Investigation of pharmacokinetic data of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin revealed from single and multiple oral dose studies with a hypericum extract containing tablet in healthy male volunteers.  Drug Res. 2005;  55 561-568
    PubMedSearch in Google Scholar
  • 33 Schulz V, Hänsel R, Tyler V E. Rational Phytotherapy. 4th ed Springer Berlin; 2001: 64-70
    Search in Google Scholar
  • 34 Schulz V. Clinical trials with hypericum extracts in patients with depression-results, comparisons, conclusions for therapy with antidepressant drugs.  Phytomedicine. 2002a;  9 468-474
    CrossrefPubMedSearch in Google Scholar
  • 35 Schulz V. Incidence and Clinical relevance of the interactions and side effects of hypericum preparations.  Phytomedicine. 2001b;  8 153-160
    PubMedSearch in Google Scholar
  • 36 Schulz V. Klinische Studien mit Hypericum-Extrakten bei Patienten mit Depressionen.  Z Phytother. 2002b;  23 11-15
    PubMedSearch in Google Scholar
  • 37 Schulz V. The psychodynamic and pharmacodynamic effects of drugs: A differenciated evaluation of the efficacy of phytotherapy.  Phytomed. 2000;  7 73-81
    PubMedSearch in Google Scholar
  • 38 St. John’s Wort (Hypericum perforatum). St. John’s Wort. Quality Control, Analytic and Therapeutic Monograph. American Herbal Pharmacopoeia and Therapeutic Compendium 1997: 1-32
    Search in Google Scholar
  • 39 Stolk P, Ten Berg M J, Hemels M E, Einarson T R. Meta-Analysis of Placebo Rates in Major Depressive Disorder Trials.  Ann Pharmacother. 2003;  37 1891-1899
    CrossrefPubMedSearch in Google 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 (7490) 503
    CrossrefPubMedSearch in Google Scholar
  • 41 Tylee A, Gastpar M, Lepine J P, Mendlewicz J. DEPRES II (Depression Research in European Society II): a patient survey of the symptoms, disability and current management of depression in the community. DEPRES Steering Committee.  Int Clin Psychopharmacol. 1999;  14 139-151
    PubMedSearch in Google Scholar
  • 42 Volz H P. Controlled Clinical Trials of Hypericum Extracts in Depressed Patients - an Overview.  Pharmacopsychiatry. 1997;  30 72-76
    PubMedSearch in Google Scholar
  • 43 Vorbach E U, Hübner W D, Arnoldt K H. Wirksamkeit und Verträglichkeit des Hypericum-Extraktes LI 160 im Vergleich mit Imipramin.  Nervenheilkunde. 1993;  12 290-296
    PubMedSearch in Google Scholar
  • 44 Yyldyz A, Sachs G S. Administration of antidepressants. Single versus split dosing: a meta-analysis.  J Affect Disord. 2001;  66 99-206
    CrossrefPubMedSearch in Google Scholar

Markus GastparM.D. 

Professor and Medical Director

Department of Psychiatry and Psychotherapy

University of Duisburg-Essen

Virchowstr. 174

45147 Essen

Phone: +49 201 7227 190

Fax: +49 201 7227 303

Email: m.gastpar@uni-essen.de