Get Involved
About Us
Our Members

Psychiatric Patients Treated with Herbal Combination Product Required Fewer Prescriptions for Benzodiazepines than Untreated Patients


Reviewed: Keck ME, Nicolussi S, Spura K, Blohm C, Zahner C, Drewe J. Effect of the fixed combination of valerian, lemon balm, passionflower, and butterbur extracts (Ze 185) on the prescription pattern of benzodiazepines in hospitalized psychiatric patients — A retrospective case-control investigation. Phytother Res. June 2020;34(6):1436–1445. doi: 10.1002/ptr.6618.

Stress can cause various psychiatric and somatoform (unexplained) symptoms, including sleep disturbances. Benzodiazepines are used to improve sleep; however, their long-term use can cause adverse effects. Herbal products may help improve stress-related disorders. Ze 185 (Relaxane®; Max Zeller Söhne AG; Romanshorn, Switzerland) is a combination of valerian (Valeriana officinalis, Caprifoliaceae) root, lemon balm (Melissa officinalis, Lamiaceae) leaf, passionflower (Passiflora incarnata, Passifloraceae) herb, and butterbur (Petasites hybridus, Asteraceae) root extracts and has been studied for its effects on somatoform disorders and anxiety. These authors conducted a single-center, retrospective, case-control study to investigate the effects of Ze 185 on the prescription pattern of benzodiazepines and other concomitantly prescribed drugs in hospitalized patients with psychiatric and somatoform disorders.

The authors analyzed the electronic medical records of patients older than 18 years who were hospitalized between January 2010 and May 2013 at the Clienia Private Clinic Schlössli in Zurich, Switzerland, which provides treatments for psychiatric, psychotherapeutic, and psychosomatic disorders. All patients who were treated with any dose of Ze 185 on at least one day during their clinic stay were considered cases for the study. The control population consisted of patients not treated with Ze 185 who were matched with the case patients by age, gender, length of hospitalization, and main International Classification of Diseases, Version 10 (ICD-10) F-diagnosis, indicating a mental, behavioral, or neurodevelopmental disorder. For the data analysis, the authors identified 3,252 patients, of which there were 1,548 cases who received Ze 185 treatment and 1,704 matched controls.

Each Ze 185 tablet contains 90 mg of a 90% per weight ethanolic extract of butterbur root, 90 mg of a 45% per weight methanolic extract of valerian root, 90 mg of a 50% per weight ethanolic extract of passionflower herb, and 60 mg of a 20% per weight ethanolic extract of lemon balm leaves.

The most frequent primary ICD-10 diagnosis was F3 (mood [affective] disorders), and the second-most frequent primary diagnosis was F1 (mental and behavioral disorders due to psychoactive substance use). Those diagnoses were similar between the groups. Significant between-group differences were observed for the primary diagnoses F2 (schizophrenia, schizotypal, and delusion disorders), with 101 cases and 181 controls (P < 0.001), and F4 (neurotic, stress-related, and somatoform disorders), with 185 cases and 163 controls (P = 0.028).

The effectiveness of the hospital stay was assessed using three measures of disease and symptom severity: the Clinical Global Impression (CGI) score, the Global Assessment of Functioning (GAF) score, and selected items on the Association for Methodology and Documentation in Psychiatry (AMDP) system. A significant treatment effect was seen in both groups for CGI and GAF scores at the end of the hospital stay (P < 0.001 for both). Significantly lower scores (meaning more severe symptoms) were seen for the GAF in the control group compared with the patients who took Ze 185 (P = 0.034). In both groups, each item on the AMDP system improved significantly from baseline to the end of treatment (P < 0.001).

The number of Ze 185 patients who received prescriptions for benzodiazepines as a treatment for anxiety was significantly lower than the number of patients in the control group (P = 0.006). However, more Ze 185 cases than controls were prescribed hypnotics, sedatives, and antidepressants (P < 0.001). Among those who also received hypnotics and sedatives, the valerian/hops (Humulus lupulus, Cannabaceae) extract Ze 91019 (Alluna®; Max Zeller Söhne AG) was prescribed more often for Ze 185 patients than for controls (P < 0.001).

Limitations of this study include: the different treatment durations and multiple concomitant drugs used by some of the patients; the inclusion of patient data from only one clinic; slightly different characteristics of the cases and controls at baseline; the lack of detailed adverse effect monitoring; and the possible confounding bias due to the patients’ and/or physicians’ preferences for the use of benzodiazepines or herbal drugs that could have influenced the prescription patterns.

The authors conclude that “both treatment modalities had a comparable clinical effectiveness but with significantly [fewer] prescriptions of benzodiazepines in the Ze 185 group.” However, because of the increased use of sedatives and hypnotics in the Ze 185 group, these effects should be further investigated in randomized, controlled clinical trials.