Efficacy and Tolerability of Hypericum Extract STW3 in Long-term Treatment with a Once-daily Dosage in Comparison with Sertraline (original) (raw)

Pharmacopsychiatry 2005; 38(2): 78-86
DOI: 10.1055/s-2005-837807

Original Paper

1General Psychiatric Hospital, Dept. of Psychiatry and Psychotherapy, University of Essen, Germany
2EPA Euro Pharma Auftragsforschung GmbH, Kronberg, Germany
3Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany

Further Information

Publication History

Received: 1.10.2003 Revised: 3.12.2003

Accepted: 8.8.2004

Publication Date:
02 March 2005 (online)

Objective: The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression. Methods: A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks (n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period. Results: After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 ± 1.1 for hypericum and 22.1 ± 1.1 points for sertraline) to 8.3 ± 5.5 points (hypericum) and 8.1 ± 5.6 points (sertraline) (mean ± SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary δ = 3) revealed that hypericum extract is not inferior to sertraline (P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-∞, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 ± 4.8 points (hypericum group) and 7.1 ± 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen’s Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases_,_ the investigators assessed the tolerability of hypericum extract and sertraline as ”good” or ”very good.” Conclusions: The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.

References

1 Barnes J, Anderson L A, Phillipson J D. St John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. J Pharm Pharmacol. 2001; 53 (5) 83-600
2 Biber A, Fischer H, Romer A, Chatterjee S S. Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers. Pharmacopsychiatry. 1998; 31 Suppl 1 6-43
3 Bracher A. Johanniskraut 1x täglich: Wirkung klinisch belegt/HYP611-Studie bestätigt Wirksamkeit. Verlagsbeilage Ärztliche Praxis. 2001; 51 1-4
4 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. Clinical therapeutics. 2000; 22 411-419
5 Brockmöller J, Reum T, Bauer S, Kerb R, Hübner W -D, Roots I. Hypericin and Pseudohypericin: Pharmacokinetics and Effects on Photosensitivity in Humans. Pharmacopsychiat.. 1997; 30 Supplement 94-101
6 Butterweck V, Jürgenliemk G, Nahrstedt A, Winterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Medica. 2000; 66 3-6
7 Butterweck V, Petereit F, Winterhoff H, Nahrstedt A. Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test. Planta Med. 1998; 64 (4) 291-4
8 Dienel A. Wirksamkeit von Hypericum-Extrakt WS 5570 bei Patienten mit depressiven Störungen. In : Schulz V, Rietbrock N, Roots I, Loew D (eds) Phytopharmaka VII - Forschung und klinische Anwendung. Darmstadt; Steinkopf 2002-10-22
9 DSM-IV . Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The American Psychiatric Association. Washington; 1994: 339-345
10 EME A. Note for Guidance on clinical investigation of medicinal products in the treatment of depression. CPMP/EWP/518/97. The European Agency for the Evaluation of Medicinal Products 2002
11 ESCO P. Hyperici herba St. John’s wort. ESCOP Monographie 1996
12 Fava M, Rankin M. Sexual functioning and SSRIs. J Clin Psychiatry. 2002; 63 Suppl 5 13-6
13 Guy W, ed. ECDEU Assessment Manual for Psychopharmacology. Rockville, Md; National Institutes of Mental Health 1976 Publication ADM 76 - 338
14 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23 6 - 62
15 Hübner W D, Arnoldt K H. Johanniskraut-Einjahresstudie. Zeitschrift für Phytotherapie. 2000; 21 06 - 310
16 Hypericum Depression Trial Study G roup. Effect of Hypericum perforatum (St John's Wort) in major depressive disorders - A randomized controlled trial. JAMA. 2002; 287 1807-1814
17 IC D -10. International Statistical Classification of Diseases and Related Health Problems, 1989 Revision. Geneva; World Health Organization 1992
18 Kalb R, Trautmann-Sponsel R D, Kieser M. Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial. Pharmacopsychiatry.. 2001; 34 (3) 96-103
19 Kasper S. Hypericum perforatum - a review of clinical studies. Pharmacopsychiat. 2001; 34 Suppl 1 51-55
20 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 (9) 2087-93.
21 Kommission E. Monographie Hyperici herba (Johanniskraut). Bundesanzeiger 228 05.12.1984
22 König W, Laux G. Trizyklische Antidepressiva. In: Riederer P, Laux G, Poldinger W (eds) Neuropsychopharmaka. Band 3 Springer-Verlag Berlin-Heidelberg-New York; 1993
23 Kötter H U, Möller H J, Hampel H. Sertralin: Ein moderner selektiver Serotonin-Wiederaufnahmehemmer in der antidepressiven Therapie. Arzneimitteltherapie; 17. Jahrgang Heft. 1999; 12 395-401
24 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 (1) 19-29
25 Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D. St John’s wort for depression - an overview and meta-analysis of randomised clinical trials. BMJ. 1996; 313 253-258
26 Markowitz J S, Donovan J L, DeVane C L, Taylor R M, Ruan Y, Wang J S, Chavin K D. Effect of St John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003 Sep. 17; 290 (11) 1500-4
27 Moscovitch A, Blashko C A, Eagles J M, Darcourt G, Thompson C, Kasper S, Lane R M. A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder. Psychopharmacology (Berl) 2003: [Epub ahead of print]
28 Osterheider M, Schmidtke A, Beckmann H. Behandlung depressiver Syndrome mit Hypericum (Johanniskraut) - eine placebo-kontrollierte Doppelblindstudie. Fortschritte der Neurologie/Psychiatrie. 1992; 60 210-211
29 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
30 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 (3 - 4) 119-28
31 Schmidt U, Sommer H. St. John’s wort extract in the ambulatory therapy of depression. Attention and reaction ability are preserved. Fortschr Med. 1993; 111 (19) 339-42
32 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 (2) 61-8
33 Schulz V. Clinical trials with hypericum extracts in patients with depression-results, comparisons, conclusions for therapy with antidepressant drugs. Phytomedicine. 2002; 9 (5) 468-74
34 St. John’s Wort. (Hypericum perforatum). Quality Control, Analytic and Therapeutic Monograph. American Herbal Pharmacopoeia and Therapeutic Compendium 1997: 1-32
35 Staffeldt B, Kerb R, Brockmoller J, Ploch M, Roots I. Pharmacokinetics of hypericin and pseudohypericin after oral intake of the Hypericum perforatum extract LI 160 in healthy volunteers. J Geriatr Psychiatry Neurol. 1994; 7 Suppl 1 S47-53
36 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 (3) 139-51.
37 van Gurp G, Meterissian G B, Haiek L N, McCusker J, Bellavance F. St John’s wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician. 2002; 48 905-12
38 Volz H P. Controlled clinical trials of hypericum extracts in depressed patients - an overview. Pharmacopsychiat.. 1997; 30 72-76
39 Vorbach E U, Hübner W D, Arnoldt K H. Wirksamkeit und Verträglichkeit des Hypericum-Extraktes LI 160 im Vergleich mit Imipramin. Nervenheilkunde. 1993; 12 90-296
40 WH O. Herba hyperici; WHO monographs on selected medicinal plants. Volume 2
41 Woelk H. Comparison of St John’s wort and imipramine for treating depression: randomised controlled trial. BMJ. 2000; 321 (7260) 536-9
42 Yyldyz A, Sachs G S. Administration of antidepressants. Single versus split dosing: a meta-analysis. J Affect Disord. 2001; 66 (2 - 3) 199-206
43 Zerssen D v on, Koeller D -M, Rey E -R. Die Befindlichkeits-Skala (B-S) - ein einfaches Instrument zur Objektivierung von Befindlichkeits-Störungen, insbesondere im Rahmen von Längsschnitt-Untersuchungen. Arzneimittel-Forsch.. 1970; 20 915-918

Markus Gastpar, MD

Professor and Medical Director

Dept. of Psychiatry and Psychotherapy

University of Duisburg-Essen

Virchowstr. 174

D-45147 Essen

Email: m.gastpar@uni-essen.de