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
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.
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.
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".
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.
"Its efficacy and tolerability are well established with clinical studies demonstrating activity comparable with conventional antidepressants, while lacking major side effects. As described earlier, suspected HP-related adverse events are primarily limited to mild gastrointestinal or cutaneous reactions although the overall incidence of such events is lower than side effects typically reported for tricyclic antidepressants (Kim et al., 1999) or selective serotonin reuptake inhibitors (SSRIs) (Lecrubier et al., 2002; Schrader, 2000; Woelk, 2000; Szegedi et al., 2005; Gastpar et al., 2006). In clinical studies, HP has shown effectiveness as an antidepressant that is higher than placebo in mild or moderate depression, and at least one study has suggested that HP is superior to paroxetine in the treatment of moderate to severe depression (Szegedi et al., 2005). "
"Capacity and willingness to give informed consent and to comply with study procedures were also required. Exclusion criteria were: psychosis, mania, hypomania or any other Axis I disorder except panic disorder, personality disorders, history of seizures, history of alcohol or drug abuse 1 year prior to the screening, antidepressant use up to 30 days before screening, pregnancy or lactation, age < 18 years, MADRS score < 15, recent suicide planning or attempts, although these are symptoms of depression, they are also standard exclusion criteria in depression clinical studies, including CAM trials in depression . "
[Show abstract][Hide abstract] ABSTRACT: Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day(-1) (up to 40 mg day(-1)) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were -3.04 (95% CI -6.95, 0.86) and -2.4 (95% CI -6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression.
Evidence-based Complementary and Alternative Medicine 08/2009; 2011(1741-427X):520182. DOI:10.1093/ecam/nep114 · 1.88 Impact Factor
"Table 3 Outcomes of efficacy Study Clinical response SSRI Remission Definition Hypericum Placebo Definition Hypericum SSRI Placebo Papakostas et al. (2007) A 50% reduction in total HAMD score – – – An HAMD score of 7 or less 13/45 16/47 10/39 Gastpar et al. (2006) "
[Show abstract][Hide abstract] ABSTRACT: Hypericum perforatum is a medicinal plant with established antidepressant properties. The aim of this meta-analysis was to compare the efficacy and tolerability of this antidepressant with selective serotonin reuptake inhibitors (SSRIs) as a group of standard antidepressants. For this purpose, Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies comparing efficacy and/or tolerability of Hypericum with SSRIs in the management of major depressive disorder (MDD). The search terms were: "Hypericum" or "St. John's wort" and "fluoxetine", "paroxetine", "citalopram", "serteraline", "escitalopram", or "fluvoxamine". Data were collected from 1966 to 2008 (up to June). "Clinical response", "remission", "mean reduction in Hamilton Rating Scale for Depression (HAMD) score from baseline", "total adverse events", and "withdrawals due to adverse events" were the key outcomes of interest. Thirteen randomized placebo controlled clinical trials met our criteria and were included. Comparison of SSRIs with placebo yielded a significant relative risk (RR) of 1.22 (95% confidence interval: 1.03-1.45, P=0.02) for clinical response (n=4), a non significant RR of 0.96 (95% CI: 0.71-1.29, P=0.76) for remission (n=4), and a significant effect size [weighted mean difference (wmd+)] of 1.33 (95% CI: 1.15-1.51, P<0.0001) for mean reduction in HAMD score from baseline (n=3). Comparison of Hypericum with SSRIs yielded a non significant relative risk (RR) of 0.99 (95% confidence interval: 0.91-1.08, P=0.83) for clinical response, a non significant RR of 1.1 (95% CI: 0.90-1.35, P=0.35) for remission, and a non-significant wmd+ of 0.32 (95% CI: -1.28-0.64, P=0.52) for mean reduction in HAMD score from baseline, a non significant RR of 0.85 (95% CI: 0.7-1.04, P=0.11) for any adverse events, and a significant RR of 0.53 (95% CI: 0.35-0.82, P=0.004) for withdrawals due to adverse events. Hypericum does not differ from SSRIs according to efficacy and adverse events in MDD. Lower withdrawal from study due to adverse events by Hypericum is an advantage in management of MDD.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2008; 33(1):118-27. DOI:10.1016/j.pnpbp.2008.10.018 · 3.69 Impact Factor
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