Melzer J, Schrader E, Brattström A, Schellenberg R, Saller R. Fixed herbal drug combination with and without butterbur (Ze 185) for the treatment of patients with somatoform disorders: randomized, placebo-controlled pharmaco-clinical trial. Phytother Res. March 9, 2009; [Epub ahead of print].

Somatoform disorders, also known as psychosomatic disorders, are a group of disorders where the physical symptoms cannot be explained by a physical disorder but are rather caused by psychological factors. Examples of somatoform disorders are body dysmorphic disorder, conversion disorder, hypochondriasis, somatization disorder, and pain disorder. Herbal preparations such as valerian (Valeriana officinalis) root, passionflower (Passiflora incarnata), and lemon balm (Melissa officinalis) leaf are used for their calming and anxiety-reducing effects. An herbal preparation Ze 185 (Relaxane^®; Max Zeller Söhne AG; Switzerland) contains extracts of these herbs along with butterbur (Petasites hybridus) root extract and is used to treat somatoform disorders. The purpose of this study was to evaluate Ze 185 in a randomized, placebo-controlled study and to evaluate the benefit of butterbur in the product.

Patients (n = 167) with symptoms for at least 6 months typical of somatization disorder and undifferentiated somatoform disorder according to ICD-10 criteria were enrolled from 2 German study centers. For 2 weeks, patients received placebo, Ze 185 (1 tablet, 3 times/day), or Ze 185 without butterbur extract (1 tablet, 3 times/day). One coated tablet of Ze 185 contains the dry extracts of 90 mg butterbur root (content of pyrrolizidine alkaloids below detection limit of 35 ppb [parts per billion]), 90 mg valerian root, 90 mg passionflower herb, and 60 mg lemon balm leaf. Depression and anxiety, the most common symptoms associated with somatoform disorders and typically used to monitor treatment efficacy in clinical trials, were rated by Beck's Depression Inventory and a visual analogue scale, respectively. They served as the primary outcome parameters in this study. Clinical global impression was a secondary parameter.

At baseline, the groups were similar. At study's end, compared with placebo, Ze 185 with (P ≤ 0.0001) and without butterbur extract (P ≤ 0.019), was significantly more effective at improving depression. Similarly, improvements in anxiety occurred with the herbal extract formulas with (P = 0.001) and without (P = 0.007) butterbur extract, compared with placebo. Ze 185 with butterbur was significantly more effective than Ze 185 without butterbur at improving anxiety (P = 0.024) and depression (P = 0.012). More patients using Ze 185 with butterbur reported complete and marked improvement (49%) and reported that they would use the treatment again (73%) compared with patients using Ze 185 without butterbur (14% and 67%, respectively) and placebo (2% and 24%, respectively). No serious side effects occurred. One subject treated with Ze 185 without butterbur had nausea leading to discontinuation of the intervention that was possibly related to treatment. Cardiovascular and hepatic systems were not affected.

The study shows that the inclusion of butterbur significantly improves efficacy of Ze 185 compared to its exclusion. It is debatable whether the primary outcome measures evaluated in this study are appropriate clinical outcome measures. Another limitation is that this study had a very short duration (2 weeks) and long-term efficacy cannot be determined. Typically treatment of somatoform disorders varies with the type of somatoform disorder. This study did not differentiate the type of somatoform disorder. These limitations should be considered when examining the data. However, since there is no standard therapy for these types of disorders, this formula offers an herbal pharmacotherapy option that could be incorporated into the clinical approach until a more specific treatment is established.