In this double-blind, placebo-controlled, randomized phase III clinical trial, the authors examine the effect of the proprietary standardized rhodiola rhizome extract SHR-5 on mild to moderate depression.
Each 400 mg tablet of SHR-5 contains 170 mg of rhodiola extract. SHR-5 is a standardized extract of rhodiola root that provides 4.5 mg of salidroside in 185 mg of extract.
Both SHR-5 and the placebo were manufactured by the Swedish Herbal Institute (Gothenburg, Sweden) following Good Manufacturing Practices. (SHR-5 is used in the special extract Arctic Root(r) and is available in the United States from ProActive BioProducts, Inc., Phoenix, AZ.)
The placebo contained 170 mg lactose. The study medication and the placebo were virtually identical in appearance.
Male and female patients aged 18-70 years (n=89) and diagnosed with mild to moderate depression according to the DSM-IV3 were recruited from the clinics of Erebouni Medical Center (Armenian State Medical University, Yerevan, Armenia). There is no indication if these patients were inpatients or outpatients.
During a 2-week run-in period, the patients received no medication. Then, patients were randomized to receive 2 tablets once daily of SHR-5 (340 mg/day) (n=31), 2 tablets twice daily of SHR-5 (680 mg/day) (n=29), or 2 placebo tablets once daily (n=29). The randomization method used followed the "principles of total randomization, whereby each patient was randomly assigned an integer 1-90."
The Beck Depression Inventory (BDI) and the 21-item Hamilton Rating Scale for Depression (HAMD) were used to determine depression severity only twice during the study: on Day 0 and on Day 42 of the 6-week treatment. Two patients dropped out of the trial "for non-medical reasons." No adverse effects were reported.
After 6 weeks, the HAMD scores showed that symptoms were significantly improved for the 2 groups receiving SHR-5 (P<0.0001) compared to placebo. For the low-dose SHR-5 group (340 mg/day), the average total HAMD score decreased from 24.5 to 16.0 (P<0.0001). The average total HAMD score decreased from 23.8 to 16.7 (P<0.0001) for the high-dose SHR-5 group (680 mg/day).
The placebo group showed no improvement in HAMD scores, from 24.2 at the beginning to 23.4 at the end. The reason for the total lack of mood change in the placebo group was not discussed, but is very unusual. The average total HAMD scores of the 2 SHR-5 groups were significantly different from the placebo group at the end of the study (P<0.001).
The study also measured certain secondary efficacy variables. At both dosage levels of SHR-5, people in the HAMD subgroups experienced statistically significant improvements in insomnia, emotional instability, and levels of somatization (the conversion of anxiety into physical symptoms), while such measures did not significantly change in the placebo group. In addition, the HAMD items for self-esteem were significantly improved in the high-dose SHR-5 group (P=0.0002).
Both treatment groups also experienced statistically significant declines in mean BDI scores (from 12.2 to 7.1 in the lower-dose group and from 10.4 to 4.8 in the higher-dose group). The subjects in the placebo group did not show statistically significant decreases in BDI scores by the end of the trial.
This clinical trial shows that the special rhodiola rhizome extract SHR-5 "possesses a clear and significant anti-depressive activity in patients suffering from mild to moderate depression." In addition, the extract appears to be safe for short-term use, with no adverse effects reported.
The authors expect that future clinical trials including a 12-week follow-up period and a larger multi-center study design will show how the efficacy of SHR-5 compares with conventional pharmaceutical antidepressants. In addition, more research is needed to confirm the mechanism of action for this observed antidepressant activity.
Richard P. Brown, MD, associate professor of clinical psychiatry at the Columbia University College of Physicians and Surgeons and a co-author of a review article in HerbalGram1 and a book on rhodiola,4 states, "In addition to mood elevation, evidence indicates that R. rosea has numerous other benefits, including enhancement of cognitive function, sexual function, and both mental and physical performance under stress.
Additional studies are needed to explore and establish the potential applications of this herbal extract. In the meantime, phytomedicinal researchers and consumers can be encouraged by these findings" (R. Brown e-mail to M. Blumenthal, November 19, 2007).
A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Standardised Extract SHR-5 of the Roots of Rhodiola rosea in the Treatment of Subjects with Stress-Related Fatigue.
Department of Psychology, Uppsala University, Uppsala, Sweden.
The aim of the study was to assess the efficacy of the standardised extract SHR-5 of roots of RHODIOLA ROSEA L. in the treatment of individuals suffering from stress-related fatigue. The phase III clinical trial took the form of a randomised, double-blind, placebo-controlled study with parallel groups. Participants, males and females aged between 20 and 55 years, were selected according to the Swedish National Board of Health and Welfare diagnostic criteria for fatigue syndrome.
A total of 60 individuals were randomised into two groups, one ( N = 30) of which received four tablets daily of SHR-5 extract (576 mg extract/day), while a second ( N = 30) received four placebo tablets daily. The effects of the extract with respect to quality of life (SF-36 questionnaire), symptoms of fatigue (Pines' burnout scale), depression (Montgomery -Asberg depression rating scale - MADRS), attention (Conners' computerised continuous performance test II - CCPT II), and saliva cortisol response to awakening were assessed on day 1 and after 28 days of medication. Data were analysed by between-within analyses of variance. No serious side effects that could be attributed to the extract were reported.
Significant post-treatment improvements were observed for both groups (placebo effect) in Pines' burnout scale, mental health (SF-36), and MADRS and in several CCPT II indices of attention, namely, omissions, commissions, and Hit RT SE. When the two groups were compared, however, significant effects of the SHR-5 extract in comparison with the placebo were observed in Pines' burnout scale and the CCPT II indices omissions, Hit RT SE, and variability. Pre- VERSUS post-treatment cortisol responses to awakening stress were significantly different in the treatment group compared with the control group.
It is concluded that repeated administration of R. ROSEA extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome. CCCPT II:Conners' computerised continuous performance test II HPA:hypothalamic-pituitary-adrenal ICD:International Classification of Diseases MADRS:Montgomery-Asberg depression rating scale Qol:quality of life.
Rhodiola Extract May Combat Depression
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