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- Rhodiola (Rhodiola rosea, Crassulaceae)
- Chronic Fatigue
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Date:
01-31-2018 | HC# 071752-585
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Re: Exploratory Trial Suggests Rhodiola May Benefit Prolonged or Chronic Fatigue
Lekomtseva
Y, Zhukova I, Wacker A. Rhodiola rosea
in subjects with prolonged or chronic fatigue symptoms: results of an open-label
clinical trial. Complement Med Res. February
2017;24(1):46-52.
Fatigue
is defined as feeling tired or lacking energy, emotional stability, or
motivation, and/or having difficulty in concentration and memory. Prolonged
fatigue is defined as fatigue lasting 1 to 6 months, while chronic fatigue
lasts for > 6 months. There is no standard treatment for fatigue of unknown
etiology. Treatment often involves exercise or cognitive behavioral therapy. Stress
may precipitate the onset of prolonged/chronic fatigue. Adaptogens, which
increase resistance to stress, may treat prolonged or chronic fatigue. The
objective of this open-label,
single-arm, multicenter study was to evaluate the effect, safety, and
tolerability of the adaptogen rhodiola (Rhodiola
rosea, Crassulaceae) root extract on patients with prolonged or chronic fatigue.
Patients
with prolonged or chronic fatigue symptoms were recruited from neurology
departments of 5 hospitals in the Ukraine. Study dates were December 2011 to May
2012. Included patients had (1) fatigue symptoms lasting for at least 2 months
that were not the result of a diagnosed illness or exertion, not adequately relieved
by rest, and interfering with major life activities; (2) a score of ≥ 5 on the Numeric
Analog Scales (NASs) for "postexertional malaise lasting more than 24
hours," "substantial impairment in short-time memory and concentration,"
and "unrefreshing sleep"; (3) Multidimensional Fatigue Inventory 20
(MFI-20) score ≥ 7 for the subscales "general fatigue," "physical
fatigue," and "mental fatigue"; and (4) the ability to respond
to interview questions and complete self-assessment scales without assistance
of an interpreter.
Excluded
patients (1) participated in another drug trial; (2) were currently
hospitalized; (3) had Beck Depression Inventory II (BDI-II) item 9 ≥ 1; (4) had
substance abuse or dependence within the last 5 years; (5) had Axis I disorders
according to the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition, within 1 year; (6) had non-medical psychiatric treatment within 4
weeks; (7) could not discontinue or might need any psychotropic drugs; (8) had clinically
significant abnormal electrocardiography (ECG) or laboratory values; (9) had cardiovascular
disease, respiratory disease, metabolic disorders, progressive disease, cerebrovascular/neurologic
disease, any infection, or gastrointestinal condition that may affect absorption
of orally administered drugs; (10) were pregnant or lactating, or, if female
and premenopausal, would not agree to use "sufficient" contraception;
or (11) had known hypersensitivity to rhodiola.
Patients
received 400 mg/day dry ethanolic rhodiola extract (WS® 1375; Rosalin®;
Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) for 8 weeks; one 200-mg
tablet was taken before breakfast and 1 before lunch. The following assessments
were conducted at baseline and at 1, 4, and 8 weeks: MFI-20 to measure fatigue;
NASs to measure chronic fatigue symptoms; Numbers Connecting Test (NCT) to
assess the speed of executive function; Sheehan Disability Scale (SDS) to assess
how panic, anxiety, depression, or phobia disrupt the patient's work, social
life, and family life; and the Clinical Global Impressions (CGI) scale with the
items "change from baseline," "therapeutic efficacy," and
"tolerability" assessed in an interview. At 4 and 8 weeks, the
following 3 additional assessments were conducted: the Pittsburgh Sleep Quality
Index (PSQI) to assess sleep quality and disturbances; Recent Perceived Stress
Questionnaire (PSQ-R) to assess subjective stress; and the BDI-II to assess depression.
Safety and tolerability were assessed via physical examinations, laboratory
data, and vital signs measurements between baseline and week 8, and assessment
of adverse events (AEs).
Of
101 patients enrolled, 1 was removed early for violation of exclusion criteria,
while 100 (mean age, 37.8 years [67% female]) completed the study. Treatment
compliance was good. The MFI-20 assessment had significant improvement on all
subscales (P < 0.0001), with the greatest change occurring at the end of
week 1, but improvement continuing to week 8. The greatest change occurred on the
subscale of "general fatigue." NASs had significant improvement
between baseline and subsequent visits (P < 0.0001). The total SDS score and
measures for "impairment at work," "impairment in social life,"
and "impairment in family life" improved significantly at week 8
compared with baseline (P < 0.0001). The NCT, PSQI, BDI-II, and PSQ-R
significantly improved between baseline and week 8 (P < 0.0001 for all). The
baseline PSQ-R score indicated that the patients had significant preexisting
stress; they experienced a clinically relevant 41.8% mean reduction in total
stress. Among the PSQ-R subscores, "fatigue" decreased by 38.8% at
week 8. On the CGI, 83.0% of patients were reported to be "very much"
or "much" improved at week 8. Approximately 41% of patients had a
total of 44 AEs, of which 81.8% were mild, with 72.7% of AEs assessed as "not
related" to the treatment and causality for the remainder unknown but
generally considered "unlikely." None of the patients discontinued
the study due to an AE. The 3 most common categories were gastrointestinal
symptoms, nervous symptoms, and "infections and infestations." There
were no clinically relevant changes in laboratory parameters, 12-lead ECG, or vital
signs.
Nearly
all outcome measures significantly improved over time and continued to decline to
week 8, and the treatment was safe and well tolerated. Taken together, the
authors conclude that the significant improvement in measures not only of core
fatigue symptoms but a broad variety of symptoms and consequences of fatigue
suggests a good potential for rhodiola to improve quality of life in chronic
fatigue. An important limitation of this study is that it was open-label; thus,
a placebo effect cannot be ruled out, nor can simple reversion to the mean in
patients whose symptoms were not of long standing. The authors acknowledge that
the study is exploratory.
The
study was funded by Dr. Willmar Schwabe GmbH & Co. KG. One of the authors (Wacker)
is an employee of Dr. Willmar Schwabe GmbH & Co. KG; another author (Lekomtseva)
received remuneration for serving as the lead investigator in this trial; and
the other author (Zhukova) received honoraria from Dr. Willmar Schwabe GmbH
& Co. KG.
—Heather S. Oliff,
PhD
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