St John's wort for depression-an overview and meta-analysis of randomised clinical trials
Linde K; Ramirez G; Mulrow CD; Pauls A; Weidenhammer W; Melchart D
Projekt Munchener Modell, Ludwig-Maximilians-Universitat, Munich, Germany
BMJ (ENGLAND) Aug 3 1996, 313 (7052) p253-8
OBJECTIVE-To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. DESIGN-Systematic review and meta-analysis of trials revealed by searches. TRIALS-23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. MAIN OUTCOME MEASURES-A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. RESULTS-Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. CONCLUSION-There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.
Treatment of depressive symptoms with a high concentration hypericum preparation-a multicenter placebo-controlled double-blind study
Witte B; Harrer G; Kaptan T; Podzuweit H; Schmidt U
Arbeits- und Forschungsgemeinschaft fur Arzneimittel-Sicherheite. V., Koln
Fortschr Med (GERMANY) Oct 10 1995, 113 (28) p404-8,
In a multicenter, placebo-controlled double-blind trial, the effect on depression (ICD 10 F 32.1) of treatment with an innovative highly concentrated hypericum preparation was investigated. The study contained 97 outpatients who received 100 to 120 mg of the hypericum extract bid. The course of the illness was assessed with the Hamilton Depression Scale (HAMD), the von Zerssen Depressivity Scale (D-S) and the Clinical Global Impression Scale (CGIS). Treatment resulted in an appreciable improvement in the symptoms of depression, and the 70% response rate (n = 43), corresponded to that of chemical antidepressants. The preparation also showed an anxiolytic effect. The substance was extremely well tolerated, and no side-effects were reported by any of the patients.
Hypericum in the treatment of seasonal affective disorders
Martinez B; Kasper S; Ruhrmann S; Moller HJ
Psychiatrische Universitatsklinik Bonn, Germany
J Geriatr Psychiatry Neurol (U.S.) Oct 1994, 7 Suppl 1 pS29-33,
Seasonal affective disorder (SAD) represents a subgroup of major depression with a regular occurrence of symptoms in autumn/winter and full remission in spring/summer. Light therapy (LT) has become the standard treatment of this type of depression. Apart from this, pharmacotherapy with antidepressants also seems to provide an improvement of SAD symptoms. The aim of this controlled, single-blind study was to evaluate if hypericum, a plant extract, could be beneficial in treating SAD patients and whether the combination with LT would be additionally advantageous. Patients who fulfilled DSM-III-R criteria for major depression with seasonal pattern were randomized in a 4-week treatment study with 900 mg of hypericum per day combined with either bright (3000 lux, n = 10) or dim (< 300 lux, n = 10) light condition. Light therapy was applied for 2 hours daily. We found a significant (MANOVA, P < .001) reduction of the Hamilton Depression Scale score in both groups but no significant difference between the two groups. Our data suggest that pharmacologic treatment with hypericum may be an efficient therapy in patients with seasonal affective disorder.
Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160
Hansgen KD; Vesper J; Ploch M
Institut fur Psychologie, Universitat Fribourg/Schweiz, Germany
J Geriatr Psychiatry Neurol (U.S.) Oct 1994, 7 Suppl 1 pS15-8,
Seventy-two depressive patients of 11 physicians' practices were treated in a double-blind study for a period of 6 weeks either with hypericum extract LI 160 or with placebo. Inclusion criterion was a major depression in accordance with DSM-III-R. The changes were assessed using four psychometric scales (HAMD, D-S, BEB, CGI). After 4 weeks of therapy, the statistical evaluation revealed a significant improvement in all four psychometric tests in the active group as compared to the placebo group. After switching the placebo group to active treatment (5th to 6th week of therapy), significant improvements were found in the original placebo group. No serious side effects were observed.
Natural product formulations available in europe for psychotropic indications
Psychopharmacology Bulletin (USA), 1995, 31/4 (745-751)
Until the middle of this century, development of medical treatment for human disease was intimately connected with the plant kingdom. Despite advances of the last three decades in utilizing chemical synthetic approaches to drug design and sophisticated structure-activity studies, there is still a great need for novel compounds with unique mechanisms of action in the field of medicine. While many thousands of structural analogs have been synthesized and tested, numerous gaps remain in the therapeutic armamentarium for psychiatric illnesses. Most new drugs marketed for psychotherapeutic indications in recent years have been only incremental improvements on existing medications. Major breakthroughs have resulted primarily from the study of natural products. Some of our most valuable drugs have been isolated from plant and animal sources, including aspirin, morphine, reserpine (the first antipsychotic), almost all of our antibiotics, digitalis, and such anti-cancer agents as vincristine, vinblastine, and taxol. Recent political and social events suggest that new emphasis will be placed on natural products research in the years to come. This article highlights therapeutic applications of Ginkgo biloba, Hypericum perforatum, Valerian officinalis, and Panex ginseng.
Antidepressive effectiveness of a highly dosed hypericum extract
Munchener Medizinische Wochenschrift (Germany), 1996, 138/3 (35-39)
Study objective: Clinical effectiveness of the hypericum extract LI 160 in cases of mild and moderate depression. Design: Randomized, double-blind placebo-controlled study with subsequent active medication in both patient groups. Patients: 102 outpatients with major depression in mild or moderate form according to DSM-IIIR. Intervention: Daily dosage 3 x 1 coated tablet LI 160 (equivalent to 900 mg hypericum extract) or placebo for four weeks with subsequent two weeks active medication in both medication groups. Endpoint: Changes of depressive symptoms according to psychometric tests. Main results: The total Hamilton score in the active treatment group fell significantly (p < 0.001) further (from 21.0 to 8.9) after four weeks than in the placebo group (from 20.4 to 14.4). Significant differences were also shown for v. Zerssen's depressivity scale (D-S) and when evaluating the level of symptoms (p < 0.01). The four-week placebo phase was followed by a two week active medication phase in both groups. This also led to a reduction in symptoms in the placebo group that correlated with the changes observed in the verum group during the first two weeks of treatment. Side ffects, in the form of slight sleep disturbances, were only reported by one patient in the verum group. Conclusion: On account of its antidepressive effectiveness and very good tolerability, the hypericum extract LI 160 can be recommended for treating patients with mild to moderate depression.
St. John's Wort in the treatment of depression
Fortschritte der Medizin (Germany), 1995, 113/25 (32-33)
St. John's Wort (Hypericum perforatum) has been used to treat a variety of complaints since ancient times. Recent studies have shown that it is clinically effective for the treatment of the symptoms of depression. It has proved superior to placebo, equally as effective as standard medication and has a clear advantage over the latter in terms of side-effects. It follows that, on the basis of our present knowledge, St. John's Wort can be recommended for use as an anti-depressant.
Fitoterapia (Italy), 1995, 66/1 (43-68)
H. perforatum is a medicinal plant which has been known in traditional medicine as antiinflammatory and healing agent. Nowadays purified extracts of its aerial parts are used for their antidepressant activity. Furthermore the antiviral activity of hypericin is currently under investigation. This review deals with the botany, chemistry, pharmacology and the clinical efficacy of H. perforatum extracts and of their active constituents, namely hypericin and pseudohypericin.
Psychomotoric performance improvement: Antidepressant therapy with St John's wort
THERAPIEWOCHE (Germany), 1995, 45/2 (106+108+110+112)
The following study investigated the influence of a herbal antidepressant containing Hypericum extract, on the cognitive performance in patients with anxiety depression. In the course of the 4-week treatment, the patients showed a reduction in both the state of anxiety and depression. The responder rate determined with the Hamilton Depression Scale was nearly 70%. Tolerance was very good. There weren't observed any adverse drug effects. The psychometric tests well established in traffic medicine could show, in comparison with the untreated control group, that the antidepressant therapy did not impair concentration nor reactivity. The data from the responder group indicates that the antidepressant therapy even caused an increase in complex cognitive performances which exceed the known training effect of these tests.
Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: A multicenter double-blind study
J. GERIATR. PSYCHIATRY NEUROL. (Canada), 1994, 7/SUPPL. 1 (S24-S28)
A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints.
Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: Randomized double-blind study with 135 outpatients
J. GERIATR. PSYCHIATRY NEUROL. (Canada), 1994, 7/SUPPL. 1 (S19-S23)
In a double-blind comparative study, 135 depressed patients were treated in 20 centers. Inclusion diagnoses were typical depressions with single episode (296.2), several episodes (296.3), depressive neurosis (300.4), and adjustment disorder with depressed mood (309.0) in accordance with DSM-III-R. The dosage was 3 x 300 mg hypericum extract LI 160 or 3 x 25 mg imipramine daily. The treatment lasted for 6 weeks. Main assessment criteria were the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S) and the Clinical Global Impressions (CGI). In both treatment groups, a parallel reduction of the Hamilton score from 20.2 to 8.8 (LI 160, n = 67) or from 19.4 to 10.7 (imipramine, n = 68), and the transformed D-S point values from 39.6 to 27.2 (LI 160) and 39.0 to 29.2 (imipramine) were found. The analysis of CGI revealed comparable results in both treatment groups. Clinically relevant changes of the safety parameters were not found. In the LI 160 group fewer and milder side effects were found as compared to imipramine.
Hypericum treatment of mild depressions with somatic symptoms
J. GERIATR. PSYCHIATRY NEUROL. (Canada), 1994, 7/SUPPL. 1 (S12-S14)
In a randomized, placebo-controlled, double-blind study, 39 patients with depression with somatic symptoms were treated with hypericum extract LI 160. The therapy lasted for 4 weeks; the dosage was 300 mg three times daily. At the onset of the study as well as after 2 and 4 weeks, the following criteria were analyzed: HAMD, B-L, CGI, and vegetative symptoms. The results show a significant improvement in the active treatment group at the 5% level as compared to placebo. Seventy percent of the patients treated with LI 160 were free of symptoms after 4 weeks. Typical symptoms of the depression such as lack of activity, tiredness, fatigue, and disturbed sleep, were especially responsive. In no case were any undesirable side effects observed.
St. Johns' wort: A prescription from nature against depressions
THERAPIEWOCHE (Germany), 1994, 44/14 (808+811-815)
The various use of St. Johns' wort, especially for depressive disorders, is based on the specific pattern of ingredients. Characteristic constituents for this plant are hypericins, hyperforine and flavonoids. These flavonoids are inhibitors of type A monoamino-oxidase in vitro. An improved utilisation of light is due to hypericin. In agreement of common experiences clinical studies prove the effectiveness of Hypericum perforatum on minor and moderate depressive disorders comparable to tricyclic antidepressants used in therapy. Therefore Hypericum perforatum represents a high potent drug for phytotherapy including good compatibility and low risk of side effects.
Extract of St. John's wort in the treatment of depression - Attention and reaction remain unimpaired
Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps165-75
Method: In a placebo-controlled, randomized, double-blind trial involving outpatients with mild to moderately severe depression, an extract of St. John's wort (Hypericum), LI 160, a herbal antidepressant was tested for efficacy and tolerability, as well as for possible negative effects on cognitive performance. Results: The responder rate to treatment with the extract was 66,6% as compared with only 26,7% with placebo. The treatment was very well tolerated; only in two patients did transient minor side effects occur under LI 160. No impairment of cognitive performance was observed: during the trial, Hypericum did not lead to any impairment of attention, concentration or reaction.
Investigations of the antidepressive effects of St. Johns Wort
PZ WISS. (Germany), 1993, 138/2 (50-54)
Extracts from Hypericum perforatum are used in the treatment of symptoms related to depressive disorders, although the active principle is not yet elucidated. Recent investigations showed a significant inhibition of MAO type-A in vitro by extracts from Hypericum. Therefore a number of Hypericum components have been tested for their MAO-inhibitory potency in vitro. The results revealed flavonoidaglyca as the active substances. The glycosides are less active, only quercitrin shows inhibition of MAO. Furthermore 1,3,6,7-tetrahydroxyxanthone was found to be a strong inhibitor of MAO A in vitro.
Experimental animal studies of the psychotropic activity of a Hypericum extract
ARZNEIM.-FORSCH./DRUG RES. (GERMANY, WEST), 1987, 37/1 (10-13)
Extracts of Hypericum perforatum (Psychotonin(Reg.trademark) M) (St. John's wort) with known concentrations of hypericin were tested in several models generally accepted as screening methods in experimental animal studies for the recognition of psychotropic, and in particular of antidepressant activity. Hypericum extract enhanced the exploratory activity of mice in a foreign environment, significantly prolonged the narcotic sleeping time dose-dependently, and within a narrow dose range exhibited reserpine antagonism. Similar to most other antidepressants, hypericum extract enhanced significantly the activity of mice in the water wheel test and after a prolonged daily administration decreased aggressiveness in socially isolated male mice. The presented data in addition to the already proven clinical efficacy justify the use of standardised Hypericum extract in the treatment of mild to moderate depression.