Herb-Drug Interactions The Good, The Bad and The Ugly

Report
Rhodiola rosea
ancient medicinal herb for stress,
mild to moderate depression
and neuro-protection
Patricia L. Gerbarg, MD
Assistant Clinical Professor in Psychiatry
New York Medical College
and
Richard P. Brown, MD
Associate Clinical Professor in Psychiatry
Columbia University College of physicians and Surgeons
Presenter Disclosures
Patricia L. Gerbarg, MD
Richard P. Brown, MD
• The following personal financial
relationships with commercial interests
relevant to this presentation existed during
the past 12 months:
• No relationships to disclose.
Defining Adaptogens
Adaptogens are herbal preparations used to:
• Protect against physical, toxic, chemical, hypoxic, heat,
cold, radiation
• Increase attention and endurance under stress
• Reduce stress-induced impairments/disorders through
actions on the neuro-endocrine- immune system.
(A Panossian & G Wikman. Curr Clin Pharmacol. 2009. 4(3):198219; AG Panossian. Psychiatric Clinics of North America. March
2013 36(1):39-64).
Molecular Mechanisms of Adaptogens
• Metabolic Regulators
• Rich in antioxidants
• Cellular repair: mitochondria, heat shock
proteins, neuropeptide Y, glucocorticoid
receptors
• Epigenetic effects
Rhodiola Rosea
Clinical Uses for Rhodiola rosea
•
•
•
•
Antidepressant solo treatment
Enhance effects of prescription antidepressants
Relieve fatigue in medically ill patients
Improve age-related decline in memory and
cognitive function
• Relieve fatigue and cognitive dysfunction caused
by antidepressants and other medications
• Increase energy, motivation
• Improve mental and physical and endurance
Additional Benefits of Rhodiola rosea
• Improve stress tolerance and resiliency for
physical and emotional stress
• Prevent/Treat Post-traumatic Stress Disorder
• ADHD – helps improve mental focus
• Improve cognitive recovery from neuro-lyme
disease
• Prevent/relieve: high altitude sickness, jet lag
• Used for sexual enhancement
• Antibacterial
SHR-5 Rhodiola rosea for Depression
• DBRPC 6-wk trial mild-mod depression
• A - 340mg/d B – 680mg/d C – placebo
Mean drop in Scores
A
B
C
HAMD 2516
2417
24  23
self-esteem
DBRPC = double-blind randomized placebo-controlled
HAMD = Hamilton Depression Scale
(Darbinyan et al. Nordic J of Psychiatry. 2007; 61(5):343-8)
Rhodiola and Intellect
• Increases production of energy (ATP and
Creatine) in mitochondria in cells of the brain,
muscles, and other organs.
• Enables brain cells to function well for longer
periods of time
• Fuels cellular repair mechanisms
(Saratikov AS, Krasnov EA (1987) Rhodiola rosea is a
valuable medicinal plant. Tomsk. Russia Pp 91-105.)
R. Rosea Improves Mental Work Capacity Under
Stress: randomized controlled studies
Improved: mental fatigue, memory, attention,
errors over time, coordination, eye fatigue, wellbeing, physical work capacity, final exam marks
Russian cosmonauts given exhausting mental
tasks reading monitors for long hours
Cadets at Russian Military Academy
Foreign high school students
Exam period fatigue/stress in college students
(Baranov VM et al. 1994; Shevtsov et al. Phytomedicine
10:95-105, 2003; Spasov AA et al. 2000, Panossian 2013;
Brown, Gerbarg. The Rhodiola Revolution. Rodale. 2004)
What is the # 1 Misconception about
Rhodiola rosea?
“Rhodiola acts as an MAOI and should
not be combined with antidepressants.”
True
False
X
Monoamine Oxidase Inhibitors (MAOIs)
• One in vitro study: a solution from a R. rosea
extract, in far greater concentration that would
occur with oral doses, had MAOI activity
• R. rosea extracts in therapeutic doses contain
such small amounts of MAOIs that they have no
clinical significance when taken by mouth
• R. rosea has been combined with all classes of
antidepressants (except MAOIs) with no adverse
effects.
(van Diermen D, et al. J Ethnopharmacology. 2009 Mar
18;122(2):397-401; A)
Rhodiola in Menopause
•
•
•
•
 energy and mood
 memory
 mental focus, “sharpness”
3 women who had been without menses
for < 12 months resumed regular
menstruation
Rhodiola & Estrogenicity
Selective Estrogen Receptor Modulator (SERM)
• Tested ovariectomized rats
• Strong estrogen receptor binding but not
activation of estrogen receptors
• No  in circulating estradiol or LH
• No change in uterine size
• R. rosea d excess estradiol levels from
estrogen implants
(Eagon PK, et al 2003. Evaluation of the medicinal
botanical Rhodiola rosea for estrogenicity [Abstract].
In American Association of Cancer Research.)
What is the # 2 Misconception about
Rhodiola rosea?
“Rhodiola rosea induces P450 enzymes
and can interfere with the metabolism
of certain prescription drugs.”
True
False
X
In Vitro, In Vivo, or In Human?
• R. rosea root extract showed in vitro inhibition of
CYP3A4 isozyme and P-glycoprotein.
• R. rosea (SHR-5) extract fed to rats (in vivo)
showed no significant effect on 2 CYP450
substrates or on warfarin anticoagulant activity.
• Adverse interactions of R. rosea with prescription
medications have not been reported in humans.
(Hellum et al., Planta Med.2010. 76(4):331-8; Panossian, et al. Planta
Med. 2009.; Kennedy, DA, and D Seely. 2010. Expert Opin Drug Saf;
Francis Brinker. 2010. Herbal Contraindications and Drug
interactions.)
R. Rosea helps kill cancer cells and protect
against side effects of chemotherapy
• Rodents with transplants of human cancers:
Lewis lung sarcoma, Pliss lymphosarcoma,
Ehrlich’s sarcoma, NKY/LY tumor, and melanoma
B16
• Given adriamycin or cyclophosphamide
• R. rosea increased chemotherapy effectiveness
• Protected liver and bone marrow stem cells from
toxic effects of the chemotherapy
(Brown, Gerbarg, Muskin. How to Use Herbs, Nutrients,
and Yoga in Mental Health. NY: WW Norton, 2009)
Breast Cancer and Ovarian Cancer
• Human Breast Cancer grafts in mice. Rhodiola
crenulata slowed growth, prevented metastasis,
induced death of breast cancer cells but not
normal human mammary epithelial cells.
• 28 women stage III-IV ovarian cancer after surgery and
1st Rx cisplatin + cyclophosphamide. 9 pts given AdMax
(L.carthemoides, R.rosea, E.senticosus, S.chinesis) had:
 CD3,4,5,8 lymphocytes,  IgG, IgM
 fatigue and depression
• 2 R. rosea compounds killed prostate cancer cells
(Y. Tu et al. J Med food. 2008; Vinalathan et al. Phytotherapy Res
2005; Kormosh et al Phytother Res 2006)
Rhodiola rosea Potential Side Effects
• Stimulative effects can be additive
– Caffeine in coffee, sports drinks
– Mild anti-platelet at higher doses (above 800 mg/day)
in some people can cause increased bruising
• Patients susceptible to stimulative effects
– Anxiety disorder, Bipolar disorder, Elderly
– Patients with underlying cardiac arrhythmia
(Panossian AG. Adaptogens in mental and behavioral disorders. Psych
Clin NA. 2013:49-64; Gerbarg & Brown. Phytomedicines for
prevention and treatment of mental health disorders. Psych Clin
NA. 2013:37-47)
R. Rosea Daily Dosages
• Healthy people to physical and cognitive
function: 50-400 mg/day
• Augment antidepressants: 300-900 mg/day
• Elderly, medically ill, anxious: start 25-50 mg,
titrate slowly as tolerated
• Response may take 1 week to 2 months
• Take most of the dose in the morning on an
empty stomach at least 20 min before a meal for
best absorption. A second dose can be taken
midday as needed
• Do not take in late afternoon or evening, as it
may impair sleep
Quality is Important
• R. rosea extracts contain hundreds of
bioactive compounds that can be destroyed or
volatilized during extraction.
• The quality of cultivated R. rosea varies
depending on climate and soil conditions
• The quality of supplements varies greatly.
• It is particularly important to use highest
quality brands to get the full benefits and
minimize side effects
Alaska
Rhodiola rosea
3-Year-Old
Plant
Summary and Future Directions
• Educate consumers and doctors regarding
benefits, HDIs, side effects, and quality products
•  interest and support for human studies:
– firmer evidence base of safety and efficacy
– Enable clinicians to extend therapeutic benefits to
patients
– new treatments for depression, fatigue, stress,
mental and physical performance, cognitive and
memory decline, cancer, space exploration
– Possible selective estrogen receptor modulator
(SERM)
“We consider ourselves phytopharmaceuticals!”
Key References -1
• Alexander Panossian. Adaptogens in Mental and
Behavioural Disorders. Psych Clin NA. 2013, 36(1): 39-64.
• Brown RP, Gerbarg PL. The Rhodiola Revolution. Rodale
press. 2009.
• Gerbarg PL, Brown RP. Phytomedicines for Prevention
and Treatment of Mental Health Disorders. Psych Clin NA.
2013, 36(1): 37-47.
• A Panossian & G Wikman. Evidence-based efficacy of
adaptogens in fatigue and molecular mechanisms related
to their stress-protective activity. Curr Clin Pharmacol.
2009. 4(3):198-219.
• Francis Brinker 2010. Herbal Contraindications and Drug
Interactions plus Herbal Adjuncts with Medicines. 4th ed.
Sandy, Oregon: Eclectic Medical Publications.
• Kennedy DA, Seely D. 2010. Clinically based evidence of
drug-herb interactions: a systematic review. Expert Opin
Drug Saf . 9 (1):79-124.
• Jerome Sarris, Panossian A, Schweitzer I, et al. Herbal
medicine for depression, anxiety and insomnia: a review
of psychopharmacology and clinical evidence. Eur
Neuropsychopharmacol. 2011,21(12):841-60.
• Gurley BJ. Pharmacokinetic herb-drug interactions (Part
1): origins, mechanisms, and the impact of botanical
dietary supplements. Planta Med. 2012; 78:1478-89

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