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Rhodiola rosea for General Anxiety Disorder
1st of 2 Reviews
By David Kiefer, MD. Dr. Kiefer is a Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; and Adjunct Faculty at Bastyr University, Seattle; Dr. Kiefer reports no financial relationships relevant to this field of study.
The successful treatment of General Anxiety Disorder (GAD) often requires a combination of a variety of modalities ranging from psychotherapy, behavior modification, pharmaceuticals, acupuncture, and/or mind-body techniques such as meditation or self-hypnosis. Practitioners and patients are also turning to dietary supplements as first-line or adjunctive therapies for GAD and, with accumulating concerns about kava kava (Piper methysticum, Family Piperaceae), other herbal medicines are rising to the occasion to treat this disorder. Rhodiola rosea is one such plant with both a rich tradition of use and clinical research suggestive of efficacy in GAD.
History and Traditional Use
There is a history of Rhodiola rosea being used in several traditional Asian and European medical systems for work enhancement, weight loss, longevity, depression, and fatigue, as well as stimulating the nervous system (promoting alertness, elevated mood) and preventing high-altitude sickness.1-3 Rhodiola rosea is used as a tonic, or adaptogen, in Russia, and is used for lung disease in Tibetan folk medicine.1,4 In 18th and 19th century France and Sweden, as well as German folk medicine, Rhodiola rosea was used as a "brain tonic" to treat headaches.5 In more modern times, there is mention in the medical literature of Russian and Scandinavian research on the impact of Rhodiola rosea on neurotransmitters and the central nervous and cardiovascular systems.2
Although Rhodiola rosea was traditionally consumed as a root/rhizome decoction,1 there are now numerous standardized and patented extracts available.
Botany and Pharmacology
There are at least 200 species in the genus Rhodiola, in the Family Crassulaceae.4 Rhodiola rosea is a small perennial native to Europe and Asia, and is primarily found at high altitudes.2,4 Like most herbal medicines, Rhodiola rosea is known by many common names, including roseroot, golden root, and Arctic root.2
Rhodiola rosea contains a phytochemical profile that is distinct, with some overlap from other species in the Rhodiola genus.6 The underground parts (referred to alternately as rhizomes or roots) of Rhodiola rosea contain organic acids, flavonoids, tannins, and phenolic compounds such as phenylpropane derivatives (rosavins, including rosavin, rosine, and rosarin) and the phenylethane derivative salidroside.3,4 One research group found 17 phenylalkanoids and monoterpene compounds in Rhodiola rosea, including one new compound which they named rhodioloside;4 some researchers consider salidroside to be the same as rhodioloside.5 Of note, salidroside is found in many Rhodiola species and other unrelated plants, whereas the rosavins appear to be specific to Rhodiola rosea.3 Alcohol extracts of Rhodiola rosea stems yield other compounds: gossypetin-7-O-L-rhamnopyranoside, rhodioflavonoside, gallic acid, trans-p-hydroxycinnamic acid, and p-tyrosol.7
Mechanism of Action
There is some evidence that Rhodiola rosea leads to changes in the levels of biogenic amines in the cerebral cortex, hypothalamus, and brain stem, possibly by inhibiting the enzymes responsible for the degradation of serotonin, norepinephrine, and/or dopamine.2,3
Studies of Rhodiola rosea root extract and its isolated phytochemicals have yielded antioxidant, anti-cancer, immune stimulating, and memory enhancement effects; some researchers have attributed the central effects of this plant to the phenolic compounds (rosavine, salidroside, p-thyrosol) and the antioxidant and anti-cancer effects to the flavonoids and organic acids.3 One study in mice demonstrated that one dose of a dry hydroalcoholic Rhodiola rosea root extract (3% rosavins, 1% salidroside) caused anti-depressant-like effects and anxiolytic-like effects, as well as increased ability to swim to exhaustion.
Rhodiola rosea is considered a promising treatment for both depression and anxiety, though many of the articles detailing these clinical effects are in foreign, difficult-to-access journals.2,8
One recent small, open-label trial followed ten people with GAD who were given 170 milligrams twice daily of a specific extract of Rhodiola (Rhodax, standardized to 30 milligrams total of rosavin, rosarin, salidrosides, rosin, rhodalgin, acetylrhodalgin, rosaridin, and rosaridol) for ten weeks.1 The Hamilton Anxiety Rating Scale (HARS) and the Clinical Global Impressions of Improvement (CGI-I) were used as the primary instruments to assess effect at baseline and at weeks 3, 6, and 10. Of note, patients could take benzodiazepines up to twice weekly and stay on their regular doses of SSRIs or SNRIs. HARS scores were significantly improved (P < 0.001) at end point when compared to baseline; half of the subjects had at least 50% improvement in their HARS scores. In addition, four of ten subjects scored a 1 (very much improved) or 2 (much improved) on the CGI-I at the end of the study. This is an interesting initial investigation, though without a placebo arm or a larger sample size, it is difficult to draw firm conclusions.
Other psychological effects
Rhodiola rosea has been evaluated in clinical trials on other psychological effects. For example, in a double-blind, placebo-controlled trial of 161 fatigued and stressed military personnel, an improvement in fatigue was noted in the group taking 2-3 tablets in a single dose of a standardized SHR-5 extract of Rhodiola rosea.5 No differences between treatment and placebo groups were noted in either psychometric testing (ie, evaluating capacity for mental work) or physiological parameters. SHR-5, approved in Denmark in 2001 for use in fatigue and convalescence, is standardized for rosavin, salidroside, and p-tyrosol content;2 for example, a 185 milligram tablet contains 4.5 milligrams salidroside.
This same extract was studied in healthy physicians being tested for mental performance9 and in students stressed by exams.10 An unstated number of students were randomized to either 50 milligrams twice daily of SHR-5 for 20 days or placebo; the treatment group showed improvements in mental fatigue, physical fitness and neurological tests (P < 0.01), and general well-being (P < 0.05). Adverse effects were not detailed, nor was an intention-to-treat analysis performed. The study in 56 healthy physicians compared overall fatigue (using the Fatigue Index, incorporating measurements of overall mental fatigue and cognitive function) after 170 milligrams of SHR-5 (approximately 4.5 milligrams salidroside) once daily for two weeks, or placebo, in a double-blind, crossover design. Though the results were reported as "significant," statistically the P-values were non-significant between treatment and placebo groups; it should be noted that numerous, complicated sub-group analyses were undertaken to elicit some positive effects between certain individuals and specific tests; these results need to be corroborated. No adverse effects were noted in either the placebo or Rhodiola rosea group.
Dosages and Forms
Some guidance about the adequate dose of Rhodiola rosea for GAD can be extrapolated from clinical trials using specific extracts. A range of doses is seen in such trials, from 100-170 milligrams daily. One author recommends basing dosage recommendations on the content of rosavin, aiming for 3.6-6 milligrams daily.2
One trial made efforts to establish the most effective dose for Rhodiola rosea by exploring the effect of different doses of SHR-5 (185 milligrams per capsule).5 Their conclusion was that 2-3 capsules daily approximates the ideal dose to yield beneficial effects.
Adverse Effects, Contraindications, and Drug Interactions
Due to the fact that Rhodiola rosea is considered an adaptogen in some cultures, it is often dosed as such. Continuous daily use for days or months is followed by a period of abstinence (such as alternating three weeks "on" and one week "off"); the theory is that this allows for long-term use and avoids adverse effects, such as on the hypothalamus-pituitary-adrenal axis. It is difficult to determine whether that clinical recommendation helps avoid adverse effects, increases efficacy, or both.2
Insomnia, irritability, fatigue, and allergy (unspecified) have been reported, especially at higher dosages;1,2 these symptoms may appear within days of beginning Rhodiola rosea.2
Additional potential side effects are surfacing from the clinical trials. Though there was no placebo arm to which to compare the side effect profile, two people experienced dizziness and four complained of dry mouth in one study.1
Rhodiola rosea has a long history of traditional use, primarily in Europe and Asia. Extracts of the roots/rhizomes yield many phytochemicals such as organic acids, flavonoids, tannins, and phenolic compounds. Most research and standardization has focused on the phenylpropane rosavin and the phenylethane salidroside. A variety of effects on neurotransmitters have been documented in basic science research, as well as behavioral effects in animal models; both of these could account for the psychological effects alluded to in traditional medicine and beginning to be studied in clinical trials. Only one open-label trial investigating the use of Rhodiola rosea exists for GAD. Although the effect was favorable, these results need to be corroborated.
Rhodiola rosea is a fascinating plant with a respectable number of phytochemical investigations and demonstrated psychotropic effects, but very little human clinical research has yet been performed with the agent. Rhodiola rosea appears to work primarily as an adaptogen, mood enhancer, and anti-fatigue treatment. It remains to be definitively proven whether Rhodiola rosea works for GAD; thus, it should not be recommended to patients for the treatment of GAD at this time. Further clinical trials will hopefully clarify use in this setting.
1. Bystritsky A, et al. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD). J Altern Complement Med 2008;14:175-180.
2. Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev 2001;6:293-302.
3. Perfumi M, Mattioli L. Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Phytother Res 2007;21:37-43.
4. Ali Z, et al. Phenylalkanoids and monoterpene analogues from the roots of Rhodiola rosea. Planta Med. 2008;74:178-181.
5. Shevtsov VA, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine 2003;10:95-105.
6. Yousef GG, et al. Comparative phytochemical characterization of three Rhodiola species. Phytochemistry 2006;67:2380-2391.
7. Ming DS, et al. Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res 2005;19:740-743.
8. Sarris J. Herbal medicines in the treatment of psychiatric disorders: a systematic review. Phytother Res 2007;21:703-716.
9. Darbinyan V, et al. Rhodiola rosea in stress induced fatigue a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 2000;7:365-371.
10. Spasov AA, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine 2000;7:85-89.