There have been hundreds and hundreds of studies and clinical trials in using botanicals for the treatment of Depression, PMS and Migraines, this article is a scientific look at the results from some of those studies. If you choose to explore a natural route to healing these symptoms this information could be invaluable.
Botanicals to be Discussed
• Migraines
– Feverfew
– Ginger
– Butterbur
• Depression
– St. John’s wort
– Ginkgo
– Lemon balm
– Black cohosh
– Red clover
– Rhodiola
Distribution of Migraine Types in Women
• 40% non-menstrual migraines
• 60% menstrual migraines
• Menstrual related migraines = majority of the pure menstrual migraines (46% of 60%)
• Other hormonal migraines: pregnancy, postpartum
Migraine Influences
• Hormones, especially estrogen changes
• Serotonin
• Abnormal platelet function
• Release of substance P
• Triggers
Treatment Considerations
• Lifestyle/Dietary factors
• Nutritional Supplements
– Riboflavin
– Magnesium
– 5-HTP
– Pyridoxine
• Botanicals
– Feverfew
– Ginger
– Butterbur
• Hormones
– Estradiol
– Estradiol patches
• Pharmaceuticals
– OTC, Rx
Feverfew
• Principal lactone
– Parthenolide
• Inhibits
– Prostaglandins, leukotrienes, thromboxanes, platelet aggregation
• Tonifies
– Vascular smooth muscle
• Dose
– 125 mg dried feverfew standardized to 0.2% parthenolide content
Feverfew – 1983 Survey
• N=300 (5 of 6 female)
• Users ate one to four fresh leaves daily
• Questionnaire:
– Less frequent 72%
– Less painful 72%
– Unchanged 24%
– Worse 2%
Feverfew
• N=17 migraine patients who had been using
feverfew prophylactically
• Study: 50 mg feverfew vs placebo x 6 mo.
• Results: relief with feverfew; three fold
increase in migraines with placebo
Feverfew
• N=72
• Tx
– 1 capsule dried leaf vs placebo
– 4 months
– Double blind cross over
• Results
– Mean reduction in number and severity of attacks
– Reduction in vomiting
Ginger
• Gingerols and shogaols
• Inhibits
– Platelet aggregation
– Prostaglandin synthesis
– Leukotriene biosynthesis
• Dose
– 500 mg qid; 100-200 mg tid if standardized to contain 20% gingerol and shogaol; or 200 mg every 2 hours up to 6 times daily for acute migraine
Butterbur Root
• N=60
• Butterbur 50 mg bid vs Pl for 12 wks
• Evaluation: frequency, duration, intensity, analgesic use, adverse events
• Results (frequency):
4 wks 8 wks 12 wks
BB= 46% 60% 50%
P= 24% 17% 10%
Global assess p<0.01
Duration and intensity diminished but not statistically significant
• Adverse event: None
Migraines – Sample Treatment Plan
• Determine and avoid food sensitivities
• Determine and reduce other triggers
• Increase therapeutic foods
• Butterbur 50 mg bid and/or feverfew 1 capsule/d and/or ginger 1 capsule qid
• Magnesium 600 mg daily
• Riboflavin 400 mg/day
• 5-HTP 200-600 mg daily h.s.
• Use of estrogen patch or other delivery as appropriate
• Tylenol, Advil, Imitrex or other as needed for attacks
Migraines – 2 Day Premenstrual Migraine
Sample plan
• Determine and avoid food sensitivities
• Determine and reduce other triggers
• Increase therapeutic foods
• Butterbur 50 mg bid and/or fever few 1 capsule/d and/or
ginger 1 capsule qid
• Magnesium 600 mg daily
• Riboflavin 400 mg/day
• 5-HTP 200-600 mg daily h.s.
• Combo PMS product and/or Estradiol patch 0.025 (consider
.0375 or .05 mg) day 21
Perimenopausal Migraine
• Age 48
• Shorter menstrual cycle or 24-35 day cycle
• HA onset midcycle and before/during/or right after menses
• Other common symptoms= moderate VMI, weepy, insomnia
TX:
• Determine and avoid food sensitivities
• Determine and reduce other triggers
• Increase therapeutic foods
• Butterbur 50 mg bid and/or feverfew 1 capsule/d and/or ginger 1 capsule qid
• Magnesium 600 mg daily
• Riboflavin 400 mg/day
• 5-HTP 200-600 mg daily h.s.
• Menopause combo botanical formula and/or Estradiol patch 0.0375-0.05
mg patch day 14 and day 21
Depression – Organic and Physiologic Causes
• Food allergies
• Heavy metals
• Nutritional
• Medications
• Recreational drugs
• Alcohol; Nicotine
• Sleep problems
• Stress-relationship, economics, job, loss, home
• Trauma
• Medical conditions
– New serious diagnosis
– Life altering/threatening illness
– Infections
– Chronic pain
– PMS, post partum
– Perimenopause/early
menopause
– MS, RA, DM, COPD,CAD, CHD, hypothyroid, insomnia, sleep apnea
Nutritional Supplements
• L-Tryptophan
• 5-HTP
• Phenylalanine
• Tyrosine
• S-Adenosyl-Methionine (SAMe)
• B12, B6, folic acid
• Magnesium
• Fish oils
Botanicals
• St. John’s wort
• Ginkgo
• Lemon balm
• Black cohosh
• Red clover
• Rhodiola
St. Johns wort – Antidepressant Activity
• Indications
– mild-moderate depression; major depression?; SAD; PMDD
• 4 mechanisms of action
– Inhibition of MAO
– Modulation of IL-6
– Inhibition of serotonin reuptake
– Agonist action of sigma receptors
St. John’s wort Clinical Trials
Cochrane Review 2006 (Last update Feb 2005)
• 37 trials: 26 comparisons with placebo and 14 comparisons with standard
Rx antidepressants
• Major depression: RR for hypericum compared with placebo was 1.15 (95% CI, 1.02-1.29) and 2.06 (95% CI, 1.65-2.59)
• Mild to moderate depression: RR 1.71 (95% CI, 1.40-2.09) and 6.13 (95%
CI, 3.63 and 10.38).
• SJW vs. SSRIs and TCA: RR 0.98 (95% CI, 0.85-1.12); and 1.03 (95% CI, 0.93-
1.14).
-Lower drop out rate with SJW
-Similar results and not statistically significant between SJW and SSRIs (OR
0.60, 95% CI, 0.31-1.15)
• Conclusions:
– Scientific evidence is inconsistent, confusing
– Major depression-SJW minimal effects in some trials while others suggest similar effects to SSRIs
St. John’s wort and PMS
• N= 19
• Evaluation
– Hospital Anxiety and Depression scale
– Modified Social Adjustment Scale
– Baseline and after one and two tx cycles
• Dose
– 300 mg .3% hypericin, 1 tablet daily
St. John’s wort and Chaste tree for PMS Symptoms in Peri-menopausal Women
• 16 weeks and information; perimenopausal
• Dose: SJW=3 tablets containing 5400 mg of St. John’s wort standardized to contain 990 mcg hypericins, 9 mg hyperforin and 18 mg flavonoid glycosides. The daily dose of chaste tree berry was one tablet of an extract equivalent to 1000 mg of dry fruit.
• The active treatment group was statistically superior to placebo for total PMS-like symptoms as well as subgroups of PMS depression and PMS food cravings.
SJW in Menopause
• Non placebo controlled, drug monitoring study was conducted in women with menopause symptoms and found that 900 mg of St. Johns wort for 12 weeks significantly improved psychological and psychosomatic symptoms as well as a feeling of sexual well- being.
St. John’s wort Extract – Safety Update
• Advise patients not to take SJW with SSRIs – there have been
several cases of serotonin syndrome reported in the literature
that may have been caused by concomitant use.*
my opinion- only avoid if 2 SSRIs + SJW
• Warnings about use of SJW with anesthesia may be unfounded due to the fact that the herb has no in vivo MAOI activity. **
• Two separate publications report on a total of 5 case reports
of patients showing the onset of mania following the use of
St. John’s wort extract for depression.
• As is the case with other antidepressants, health care professionals should screen patients for a history of hypomania or mania before prescribing St. John’s wort.
St. John’s wort Extract Potential Drug Interactions – Mechanism?
• The unanimous theory surrounding the SJW drug interactions has been its supposed interaction with the cytochrome P450 enzyme system and particularly induction of CYP 3A4. (Clin Pharmacol Ther 2000;67:451-7). One study seems to contradict these findings (Pharmacol Letters
2000;66:133-9).
• CYP3A4 is the most abundant cytochrome P450 isoenzyme and is responsible for the metabolism of more than 73 drugs. Key among these are protease inhibitors, calcium channel blockers, benzodiazepines, cyclosporine, cortisone, nonsedating antihistamines, 3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitors, estrogens, macrolide antibiotics, carbamazepine, and ketaconazole.
St. John’s wort Extract Potential Drug Interactions
•Case reports and/or pharmacological studies have indicated that SJW may reduce serum levels of the following drugs (most likely due to induction of CYP3A4 and P-glycoprotein):
– Indinavir (Crivaxin®) (Lancet 2000;355:547-8)
– Cyclosporine (Lancet 2000;355:548-9; Lancet 2000;355:1912; J
Hepatology 2000;33:853-5; Ann Pharmacother 2000;34:1013-6).
– Tacrolimus (immunosuppresant) (Nephrol Dial Transplant 2003;18:819-
22).
– Theophylline (Ann Pharmacother 1999;33:502)
– Digoxin, warfarin, oral birth control pills (Eur J Clin Pharmacol
1999;55:A22; Clin Pharmacol Ther 1999;66:338-45; Lancet
1999;354:2014-6; J Clin Pharmacol 2003;56:683–90).
– Irinotecan (chemotherapeutic drug) (J Natl Cancer Inst 2002;94:1247–9).
– Gleevec (chemotherapeutic drug – U. of Florida report)
Ginkgo Biloba
• Active constituents:
– ginkgo – flavone glycosides or ginkgo heterosides (flavonoid molecules with sugars attached)
– terpene molecules =
ginkgolides and bilobalide
– organic acids
• GBE is standardized to contain 24% flavone glycosides
Ginkgo: Pharmacological Effects
• Inhibits lipid peroxidation of cellular membranes
• Stabilizes cell membranes
• Activates the cellular membrane sodium pump
• Enhances the use of oxygen and glucose
• Enhances circulation in the hippocampus and striatum
• Increases nerve transmission rate, improves synthesis and turnover of brain neurotransmitters, normalizes acetylcholine receptors in the hippocampus and inhibits beta-amyloid
• Vascular effects: vasodilation (direct stimulation of the release
of endothelium-derived relaxing factor and prostacyclin
• Platelet effects: inhibits platelet aggregation, adhesion and degranulation, inhibits platelet-activating factor.
PMS: Ginkgo Biloba
• N= 165 women ages 18-45 with long-term PMS sxs
• Methods: GBE 80mg bid or placebo from d. 16-d.5
• Results: less breast pain or tenderness as well as improved psychological assessment.
Ginkgo and PMS
• N=85
• 40 mg three times daily of a standardized ginkgo extract or a placebo from day 16 of the cycle to day 5 of the next cycle. Self-administered questionnaires were used and a diagnosis of PMS had been established according to conventionally accepted criteria.
• Significant decrease in the overall severity of symptoms and physical and psychological symptoms in both the Ginkgo group (23.68%) and the placebo group (8.74%). The average decreased in the severity of symptoms was significantly more in the Ginkgo group compared to the placebo group.
Ginkgo Dosage
• Standardized extract containing 24% ginkgo
flavone glycosides
• 40 mg tid; some studies 80 mg tid or 120 mg
bid
• 12 weeks to determine effectiveness
Ginkgo Side Effects
• Well tolerated in most healthy adults when used in
recommended doses
• Dermatologic: allergic hypersensitivity
• Neurologic: HA, dizzy, restlessness; seizure
exacerbations
• Cardiovascular: decreased BP
• Gastrointestinal: infrequent mild GI discomfort, esp
when taken with SSRIs. Occ N/V, diarrhea
• Hematologic: documented case report bleeding
Ginkgo – Cautions/Drug Interactions
• Avoid – in those at risk of bleeding, taking
anticoagulants, clotting disorders
• D/C 2-3 weeks prior to surgical and surgical
dental procedures
• Caution – history of seizure
Lemon Balm
• Lemon balm increased cognitive ability and
mood in 20 healthy young adults.
• Doses: 600 mg, 1,000 mg and 1,600 mg per
day were given seven days apart.
• Results: Highest dose produced the most
dramatic improvements.
Black Cohosh – Clinical Research
Over 120 published scientific papers and presentations on the efficacy and safety of a standardized black cohosh extract.
Potential Mechanisms
1. Possible selective estrogen receptor modifier1
– Estrogen-like effect in brain, bone, and vaginal tissue
– Does NOT act like estrogen in breast or uterine tissue
** Has been recommended for women with a history of breast cancer who cannot take estrogen.
2. Role may be centrally mediated, with possible action at the level of serotonin or dopamine receptors.
Black Cohosh and SJW
• Average Menopause Rating Scale score decreased
50% in the treatment group/19.6% in the placebo
group. The Hamilton Depression Rating Scale score
decreased 41.8% in the treatment group/12.7% in
the placebo group.
• In both the general menopause rating scale and in the depression scale, the St. John’s wort + black cohosh group was significantly superior to the placebo group.
Black Cohosh/St John’s wort
• Prospective, controlled open-label observational study
• N=6141 women at 1287 outpatient gyn clinics in Germany
• Dose:
– Remifemin 20 mg tablet bid
– Remifemin plus: 3.75 mg iCR extract and 70 mg SJW (frin 245 mg to
350 mg)
• Results: Combination product > black cohosh only for mood symptoms.
Black Cohosh Dose and Safety
• Dosages: 20-40 mg St. Extract bid
• Contraindications
– None known
– Avoid during pregnancy and lactation
• Cautions: if you have liver disease
• Adverse Effects
– Occasional gastrointestinal discomfort
– Overdose may cause vertigo, headache, nausea, vomiting, impaired vision, impaired circulation
• Drug Interactions
– Caution if hepatotoxic drugs
– Avoid if Cisplatin
– Ok with tamoxifen or raloxifene
Red Clover
• 109 postmenopausal women; 2 capsules daily of a red clover extract totaling 80 mg of isoflavones, or a placebo, for 3 months.
• Hospital Anxiety and Depression Scale(HADS) and the Zung’s
Self Rating Depression Scale (SDS).
• After taking the red clover extract, women had a significant change in both of the rating scales, with a 75% reduction for anxiety and 78.3% reduction for depression using the HADS tool, and an 80.6% reduction in the total SDS score. After taking the placebo pills, the HADS and SDS scores only reduced by an average of 21.7%.
Adaptogens
• Metabolic Regulators
• Improves carbohydrate metabolism
• Counter catabolic processes associated with
any form of stress on the body
• Stimulating effect more pronounced with a background of fatigue and stress
Botanical Adaptogens
• Astragalus membranaceus
• Bupleurum falcatum
• Eleutherococcus senticosus
• Ganoderma lucidium
• Ocimum sanctum
• Panax quinqefolium
• Rhodiola rosea
• Scutellaria baicalensis
• Schisandra chinensis
• Withania somnifera
Rhodiola
• Fatigue
• Anxiety
• Depression
• Moodiness
• Physical and Mental Performance
• Protects against the effects of stress, hypoxia, extreme temperatures, intense physical activity
• Neuroprotective
Rholdiola rosea
Active Constituents:
• Rosavin, rosin, rosarin, salidroides, rhodioloside, tyrosol, flavonoids (rodiolin, rodionin), phenolic antioxidants, including proanthocyanidins, quercetin, gallic acid, chlorogenic acid and kaempferol
Actions:
• Adaptogen, anti-depressant, antioxident, anti-viral, immunomodulating, nervine, cardioprotective, neuroprotective, tonic
• Cardiovasculer system – prevents stress-induced heart damage, arrhythmia, improves cardiac output
Active Constituent of Rhodiola
• Tyrosol – active principle of Rhodiola extract – increases phosphorylation of nitric oxide and FOXO3a, a fork head transcription factor that controls synthesis of proteins involved in stress resistance, detoxication, and longevity.
• Tyrosol – acts to alleviate both stress-induced depletion of brain catecholamines in the alarm phase of stress syndrome and reduces fatigue.
Rhodiola
• Rhodiola rosea’s mood regulating effects potentially are related to optimizing serotonin and dopamine levels due to monoamine oxidase inhibition and its influence on opioid peptides such as beta- endorphins.
– Stress induced depression
– Anxiety
– Mild to moderate depression
Rhodiola and Depression
• 3 groups, 29 pt @,HAMD scores, RD-BC trial
• Rhodiola group improvement in overall depression, insomnia,emotional instability and somatization, but not self- esteem.
• Placebo group did not show such improvements.
• Concluded that the standardized extract rhodiola showed anti-depressive potency in patients with mild to moderate depression when administered in dosages of either 340 or 680 mg/day over a 6-week period.
Rhodiola Dosage
• 4-8 ml/d liquid extract
• 200-600mg/d dried root
• 100 mg of extract standardized to 3 percent rosavins and 0.8-1 percent salidroside, as the naturally occurring ratio of these compounds is approximately 3:1.
• A high dose-daily intakes of 1,000 mg
• Mild – Moderate Depression: 170 mg or 340 mg twice daily for 6 weeks*
• Anti-fatigue: 200 mg three times a day
• Insomnia: 600mg dose**
You can read more about Rhodiola here
Resources
• Natural Standard: Evidence based clinical review
• Natural Medicines Comprehensive DataBase
• PDR for Herbal Medicines
• PDR for Nutritional Supplements
• Encyclopedia of Nutritional Supplements
Murray and Pizzorno
• Textbook of Natural Medicine
Pizzorno and Murray
• Women’s Encyclopedia of Natural Medicine
Hudson
• Women’s Encyclopedia of Natural Medicine,
2008, second edition
• www.drtorihudson.com
• www.awomanstime.com
• www.instituteofwomenshealth.com
• www.naturopathicresidency.org
• DrHudson@awomanstime.com