In 2021, the phytopharmaceutical Calmalaif® received marketing authorisation in Germany with a composition that was not previously represented on the German market. The preparation contains a combination of the dry extracts of various medicinal drugs: valerian root, passion flower herb, hawthorn leaves with flowers, and black nettle herb1. This combination is recommended to improve well-being during nervous stress and to promote sleep. The current marketing authorisation is a good reason to summarise the state of knowledge here.
Real-life data: Mild sleep disturbances and mild anxiety are common
Significant benefit under real-life conditions
At the end of the 15-day treatment, a significant decrease in the frequency of both psychological and somatic symptoms that had led to medical consultation was observed (Figs. 1 and 2).
Fig. 1. Changes in psychological symptoms
Fig. 2. Changes in somatic symptoms
The PSM-9 (Psychological Stress Measure) was used to assess the stress level, in which the investigators each rated nine symptoms of their patients on an eight-point scale . The mean stress level at the time of inclusion was 50 ± 9 on the PSM-9 scale and 84.8% of patients had an elevated stress level defined according to the scale, with a score of ≥40. The mean PSM-9 score was 39 ± 11 after the 15-day treatment, resulting in a significant mean reduction of about 20% (p < 0.0001). The percentage of patients with an increased stress level (PSM-9 score >40) decreased to 44.4% compared to 84.8% before treatment (p < 0.0001) (Fig. 3).
After 15 days of treatment, the mean AIS score was 7.7 ± 5.0, resulting in an improvement in sleep of 34.7% (p < 0.001). The proportion of patients with confirmed sleep disturbances (AIS score >6) decreased from 88.2% before treatment to 55.6% (p < 0.05) (Fig. 3).
Fig. 3. Change in the percentage of patients with increased stress levels (PSM-9 >40) or confirmed sleep disorders (AIS >6)
The assessment of the changes after 15 days of taking the study medication in the nine individual symptoms of the PSM-9 showed a comparable improvement in all nine axes (Fig. 4).
Fig. 4. Change in the different axes of the PSM-9 under treatment with the quadruple herbal combination
These clinical improvements were also reflected in the patients' quality of life. The effects on daily life were determined with a visual analogue scale (VAS) (0 = no effect; 100 = intensive effect) (Fig. 5).
Fig. 5. Negative impact on professional and family life and change in general well-being before and after 15 days of therapy. Data points show the mean ± SEM in mm of a visual analogue scale (0 = no effect; 100 = intensive effect).
Placebo-controlled volunteer study: Proven benefit also under defined psychological and physiological stress situations
Complementing the non-interventional observational study, a randomised, placebo-controlled, double-blind trial was presented in a cross-over design in 2020 . Healthy adults (n = 27), without anxiety and mood disorders received either the quadruple herbal combination or placebo for 14 days, switching treatments after a 28-day wash-out period. Two tablets were taken three times a day. The aim of the trial was to investigate the effects of taking the phytopharmaceutical for two weeks on relevant psychological and physiological stress parameters.
Longer-term effects were assessed with various psychological questionnaires, and acute psychological and physiological effects were determined in response to an artificial psychosocial stress situation in the laboratory (observed multitasking stressor, OMS).
In addition, mood, sleepiness and cognitive functions were assessed via a mobile app (Cognimapp) on days 7 and 14 of the intervention period.
Phytopharmaceutical product as first-line treatment for stress symptoms
The results of the studies demonstrate the benefit of the quadrupal herbal combination as a first-line treatment for stress-related symptoms such as mild insomnia, anxiety, tension and nervous restlessness. Positive effects on psychological as well as somatic stress symptoms and an improvement in quality of life were shown in real-life data and were supported by a placebo-controlled volunteer study.
1Medically active ingredients: Dry extracts of valerian root (29 mg, 3–6:1, extraction agent 60% ethanol), passion flower herb (13 mg, 4–7:1, extraction agent 60% ethanol), hawthorn leaves with flowers (5.4 mg, 4-7:1, extraction agent water), black nettle herb (4.5 mg, 4–6:1, extraction agent water).
The study product was the product Euphytose®, which is licensed in France: dry extracts of valerian root (50 mg, extractant 60% ethanol), passion flower herb (40 mg, extractant 60% ethanol), hawthorn leaves with flowers (10 mg, extractant water), black nettle herb (10 mg, extractant water) .
Differences in the quantities stated between the two products are due to declaration requirements: In the previous authorisation of Euphytose® in France, the extract preparation including primary excipients was stated, whereas the quantities in Calmalaif® include the proportion of native extract alone .
- Allaert FA. Évaluation d’une phytothérapie dans le traitement des troubles mineurs du sommeil et de l’anxiété légère. La Lettre du Psychiatrie, Vol. V, No. 3, May-June 2009.
- Package information leaflet, Euphytose®, 2008.
- Bayer Vital GmbH, Leverkusen
- Lemyre L, Tessier R. Measuring psychological stress. Concept, model, and measurement instrument in primacy care research. Can Fam Physician 2003;49:1159–60:1166–8
- Paparrigopoulos T, et al. Insomnia and its correlates in a representative sample of the Greek population. BMC Public Health 2010;10:531. https://doi.org/10.1186/1471-2458-10-531
- Jackson P, Dodd F, Wightman E, Kennedy D. The chronic effects of a multi-herbal extract preparation on psychological and physiological measures of stress: a randomised, placebo-controlled, double blind study in healthy humans. Berlin: DGPPN, 2020
Conflict of interest: H. Aziz-Kalbhenn and C. Kolb are employees of Steigerwald Arzneimittelwerk GmbH, Darmstadt.
Disclosure: Medical writing and publication funded by Steigerwald Arzneimittelwerk GmbH, Darmstadt.