No abstract

In a prospective, multicentre trial the efficacy of an Vitex agnus castus L extract Ze 440 was investigated in 50 patients with pre-menstrual syndrome (PMS). The patients were treated daily with one tablet (20 mg native extract) during three menstrual cycles. 43 patients completed the study protocol which encompassed 8 menstrual cycles (2 baseline, 3 treatment and 3 post-treatment). 13/43 patients were receiving concomitant oral contraceptives. 6 patients did not complete the study for reasons not related to study medication, and one patient complained of fatigue possibly related to study medication. All evaluated patients took at least 85% of the prescribed medication. The main effect parameter was the validated Moos' menstrual distress questionnaire (MMDQ), and secondary parameters were a visual analogue scale (VAS; self-assessment) and a global impression scale (GI, self-assessment). The study population was homogenous in age (31.3+/-7.7 years) weight (58.9+/-6.9 kg) and cycle length (28.4+/-0.3 d). The diagnosis was according to DMS-III. At the end of the study, PMS-related symptoms were reduced by treatment. There was a significant score reduction (42.5%) of the MMDQ as the main effect parameter (p<0.001). Symptoms gradually returned after treatment cessation. However, a difference from baseline remained (20%; p<0.001) up to 3 cycles thereafter. 20/43 patients were considered "responders", with a reduction in MMDQ score by at least 50% relative to baseline. At baseline, the VAS score was elevated in the late luteal phase and low at the follicular phase, as expected. During treatment, VAS score decreased in the late luteal phase (47.2%; p<0.01) and remained 21.7% (p<0.001) below baseline after 3 cycles post-cessation of treatment. The low VAS score within the follicular phase remained unchanged over the whole observation period. 38 patients judged the global efficacy moderate to excellent, 5 patients indicated no global efficacy. The number of days patients sustained PMS symptoms was reduced slightly from 7.5 to 6. Resting levels of blood prolactin remained within the physiological range throughout. No differences were seen between patients on or off oral contraceptives. 20 patients reported 37 adverse events (AE). No serious AE were reported. One patint withdrew after four days of treatment due to fatigue and headache. Laboratory safety control parameters were not affected. In conclusion, patients with PMS can be treated successfully with Vitex agnus-castus extract Ze 440, as indicated by clear improvement in the main effect parameter during treatment and the gradual return after cessation of treatment. The main response to treatment seems related to symptomatic relief rather than to the duration of the syndrome.

Valerian and hops are traditionally used as sleep aids. Since the fixed extract combination (Ze 91019) as a whole is considered the active compound, the clinical efficacy must be demonstrated for this extract combination. The present clinical study aimed to demonstrate superiority of the fixed extract combination in comparison with placebo in patients suffering from non-organic insomnia (ICD 10, F 51.0-51.2). Objective sleep parameters were registered by means of a transportable home recorder system (QUISI). The primary outcome was the reduction in sleep latency (SL2) which had to be prolonged at baseline (>/=30 min) as an inclusion criteria. The treatment period lasted for 4 weeks with either placebo, single valerian extract (Ze 911) or the fixed valerian hops extract combination (Ze 91019). The amount of the single valerian extract was identical to that amount contained in the fixed extract combination, i.e. 500 mg valerian extract siccum. In the extract combination 120 mg hops extract siccum was added. Both the extracts were prepared with 45% methanol m/m with a drug-extract ratio of 5.3:1 (valerian) and 6.6:1 (hops), respectively. The fixed extract combination was significantly superior to the placebo in reducing the sleep latency whilst the single valerian extract failed to be superior to the placebo. The result underlined the plausibility for adding hops extract to the valerian extract.

A prospective, randomized, multicentre, double-blind placebo controlled study is described which compares the ecacy and tolerability of hypericum administered as a concentrated ethanolic extract of St John's wort (ZE117) to patients with mild±moderate depression (ICD-10; F 32 . 0 mild; F 32 . 1 moderate). Patients on active medication received 250 mg extract tablets twice daily, corresponding to 1 mg hypericin daily, for 6 weeks. The primary ecacy variable was the 21 item Hamilton Depression Scale (HAMD); secondary variables were the risk-bene®t Clinical Global Impression (CGI) scales I±III and a validated patient self-assessment on a Visual Analogue Scale (VAS). 162 patients entered the trial. 159 patients (80 on active medication) were evaluated in an intention-to-treat analysis; 136 patients (66 on active medication) in a protocol-compliant analysis. Patients in the two treatment groups did not dier with respect to the distribution of age, gender, weight and height. Based on dierences in HAMD scores ( p 5 0 . 001), both the intention-to-treat and protocol-compliant analyses demonstrate that ZE117 is clinically eective in the treatment of patients with mild to moderate depression following 6 weeks' treatment. Using the criteria of 550% reduction in HAMD score from baseline and/or an actual HAMD score 410 as evidence of a clinically relevant response, 56% patients treated with ZE117 were classi®ed as responders, compared with 15% patients on placebo. The secondary ecacy variables data con®rmed these ®ndings. Compliance was high; using electronic devices within the medication containers, a therapeutic coverage of 81 . 7% was found. This was probably due, in part, to the low number of adverse events reported (11 total, 5 placebo, 6 active), the majority of which were transient, self-limiting and, in the case of active treatment, mostly non-speci®c gastrointestinal complaints. These results demonstrate that hypericum (ZE117) provides a safe and eective treatment for patients with mild to moderate depression. The good tolerability pro®le contributes to the high observed compliance, possibly conferring a clinical advantage in achieving ecacy over other antidepressants with less favourable side eect pro®les.

Herbal drugs are often used in patients with somatoform disorders yet, the available evidence is limited. The aim of the present short-term study was to evaluate in a pharmaco-clinical trial the additional benefit of butterbur in a fixed herbal drug combination (Ze 185 = 4-combination versus 3-combination without butterbur and placebo) in patients with somatoform disorders.For a 2-week treatment in patients with somatization disorder (F45.0) and undifferentiated somatoform disorder (F45.1), 182 patients were randomized for a 3-arm trial (butterbur root, valerian root, passionflower herb, lemon balm leaf versus valerian root, passionflower herb, lemon balm leaf versus placebo). Anxiety (visual analogue scale - VAS) and depression (Beck's Depression Inventory - BDI) served as primary parameters, Clinical Global Impression (CGI) was a secondary parameter.The 4-combination was significantly superior to the 3-combination and placebo (4-combination > 3-combination > placebo) in all the primary and secondary parameters (PP-population). Analysis of the ITT population confirmed these results. As to safety, no serious adverse events occurred. In total 9 non-serious adverse events were documented but the distribution did not differ significantly between the treatment groups.This herbal preparation (Ze185) showed to be an efficacious and safe short-term treatment in patients with somatoform disorders.