Transcript Herbs for Insomnia and Anxiety

Herbs for Insomnia and
Anxiety
Kerry Bone
Co-Founder and Director Research & Development,
MediHerb
Associate Professor, University of New England,
Australia
Insomnia and Anxiety
Evidence for Key Herbs
• Kava
• Valerian
Kava and Anxiety
Cochrane Review
• A Cochrane Collaboration systematic
review in 2002 included 11 clinical
trials with a total of 645 patients1
• A meta-analysis of 6 studies that used the
Hamilton anxiety scale found a significant (p=0.01)
reduction in anxiety for kava compared to placebo
1.
Pittler MH, Ernst E. Cochrane Database Syst Rev 2003; (1): CD003383
Kava and Anxiety
Studies Published Since the Cochrane Review
• Kava was as effective as the anxiolytic drugs buspirone
and opipramol for the treatment of generalised anxiety
disorder in an 8-week randomised, double-blind trial
involving 129 patients1
• The administered dose was 400 mg/day of a kava
extract standardised for 30% kava lactones
(120 mg/day lactones)
• A lower than normal dose of kava extract (150 mg vs
300 mg) was still effective for neurotic anxiety
compared to placebo in a 4-week double-blind,
placebo-controlled trial involving 141 patients2
1. Boerner RJ, Sommer H, Berger W et al. Phytomedicine 2003; 10(Suppl 4): 38-49
2. Gastpar M, Klimm HD. Phytomedicine 2003; 10(8): 631-639
Kava and Anxiety
Studies Published Since the Cochrane Review
• The kava extract was standardised to contain 70%
kava lactones
• The lower than normal dose was tested because of
concerns that any hepatotoxic risk might be
lowered by reducing the dose
• A trial of similar design found that 150 mg of kava
extract (105 mg/day kava lactones) was an
effective treatment for non-psychotic anxiety
syndromes1
1.
Geier FP, Konstantinowicz T. Phytother Res 2004; 18(4): 297-300
Kava and Anxiety
Kava and Mood
• In an interesting study, the acute
effects of kava on emotional reactivity
and cognitive performance were investigated in a
double-blind, placebo-controlled trial involving
healthy volunteers1
• The intake of a single 300 mg dose of kava extract
(containing 90 mg of kava lactones) lead to an
increase in cheerful mood and enhanced cognitive
performance
1.
Thompson R, Ruch W, Hasenohrl RU. Hum Psychopharmacol 2004; 19(4): 243-250
Kava and Anxiety
Kava and Mood
• The authors pointed out that this was in stark
contrast to benzodiazepine drugs which tend to
impair performance and increase the occurrence of
negative feelings
Kava and Anxiety
Kava and Sleep
• A study in sleep disturbed rats found
that kava not only reduced sleep latency, but also
improved sleep quality (as assessed by EEG)1
 Kava was an effective treatment in patients with
sleep disturbances associated with anxiety in a 4week double-blind, placebo-controlled trial
involving 61 patients2
 The administered dose was 200 mg/day of extract
(140 mg/day lactones)
1.
2.
Shinomiya K, Inoue T, Utsu Y et al. Psychopharmacology (Berl) 2005; 180(3): 564-569
Lehrl S. J Affect Disord 2004; 78(2): 101-110
Valerian and Anxiety
• In a double-blind trial of 48 adults placed
in an experimental situation of social
stress, valerian reduced subjective
sensations of anxiety and did not cause
any measurable sedation1
• Valerian and kava were compared to each other
and placebo in a standardised mental stress test
in 54 healthy individuals
1.
Kohnen R, Oswald WD. Pharmacopsychiatry 1988; 21: 447-448
Valerian and Anxiety
• Unlike placebo, both preparations decreased systolic
blood pressure responsiveness and self-reported
feelings of stress, and inhibited a stress-induced rise
in heart rate1,2
• A number of early clinical trials have found that a
combination of valerian and St John’s wort was
successful in the management of anxiety and
depression3
1.
2.
3.
Cropley M, Dave Z, Ellis J, Middleton RW. Phytoher Res 2002; 16: 23-27
Valeriana officinals-Monograph. Alt Med Rev 2004; 9(4): 438-441
Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine.
Churchill Livingstone, Edinburgh, 2000, pp. 586-587
Valerian and Sleep
• Patients aged 18 to 73 years and
diagnosed with non-organic insomnia
were treated in a multicentre, double-blind,
randomised parallel group comparison with either
600 mg/day of valerian extract (5:1) or 10 mg/day
oxazepam taken for 6 weeks1
• A total of 202 outpatients with a mean duration of
insomnia of 3.5 months at baseline were included
• Sleep quality after 6 weeks showed that valerian
extract was at least as efficacious as treatment
with oxazepam
1.
Ziegler G, Ploch M., Miettinen-Baumann A et al. Eur J Med Res 2002; 7(11): 480-486
Valerian and Sleep
• Another smaller trial of similar design compared the
effect of the same dose of valerian with 10 mg
oxazepam over 4 weeks in 75 patients with nonorganic insomnia1
• The study showed no differences between the
efficacy of valerian and oxazepam
• The efficacy and tolerability of a valerian extract
preparation were investigated in an open,
observational study on children aged to 6 to 12
years2
1.
2.
Dorn M. Forsch Komplementõrmed Klass Naturheilkd 2000; 7: 79-84
Hintelmann C. Z Phytother 2002; 23: 60-61
Valerian and Sleep
• An average daily dosage of 2 tablets (range 1 to 4)
tablets containing 300 mg of 5:1 extract was
administered to 130 children suffering from nervous
sleep disturbances and/or nervous tension over a
period of 4 weeks
• Therapeutic efficacy was estimated by parents and
physicians as good to very good in 95% of cases
• Numerous earlier studies of valerian on its own or
in combination with hops, passionflower and/or
lemon balm have demonstrated improvements in
sleep parameters in controlled clinical trials1
1.
Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone,
Edinburgh, 2000, pp. 584-586
Valerian versus Benzodiazepines
• In an Australian study, nine healthy volunteers
received single doses of either valerian root
(1000 mg or 500 mg), the drug triazolam (0.25 mg)
or placebo in a double-blind, placebo-controlled,
crossover trial1
• Results confirmed that while triazolam had a
detrimental effect on cognitive processes, the
valerian was without effect
1.
Hallam KT, Olver JS, McGrath C et al. Hum Psychopharmacol 2003; 18(8): 619-625
Valerian versus Benzodiazepines
• Another study compared even higher
doses of valerian (600, 1200 and 1800 mg
of a 5:1 extract) with 10 mg diazepam
and placebo in a clinical trial of similar design1
• Again an impairment of performance occurred for
the benzodiazepine drug whereas the valerian had
no impact on any parameters tested
• A third study found that valerian (400 mg and
800 mg) was not different from placebo on any
measure used of psychomotor performance or
sedation2
1.
2.
Gutierrez S, Ang-Lee MK, Walker DJ et al. Pharmacol Biochem Behav 2004; 78(1): 57-64
Glass JR, Sproule BA, Herrmann N et al. J Clin Psychopharmacol 2003; 23(3): 260-268
Insomnia
Classification of insomnia includes:
• Difficulty falling asleep (sleep onset
insomnia)
• Awakening during the night and
experiencing difficulty falling asleep (sleep
maintenance insomnia)
• This is often characteristic of the
adrenally-depleted patient and
fibromyalgia
• A sense of not having enough sleep
(non-restorative sleep). This is often
characteristic of CFS
Insomnia
Background Issues
• Major causes of sleep-onset insomnia
include anxiety, pain or discomfort,
caffeine and alcohol
• Sleep maintenance insomnia can be linked to
depression, sleep apnoea, hypoglycaemia,
pain or discomfort and alcohol
• It is important to ensure that
the patient sleeps in a darkened,
noise-free environment
• Bed comfort
Insomnia
Background Issues
• The use of stimulants should be
reduced, especially coffee, tea, guarana and cola
drinks. Alcohol intake should also be reduced
• Unwinding at night can be important and a few
drops of Lavender oil added to an evening bath can
help this process
Insomnia
Therapeutic Strategy: Goals, Actions and Herbs
• Anxiolytic and hypnotic herbs are the
mainstay of support. These can be
taken throughout the day to prevent a
buildup of tension or mental excitability
which might result in insomnia. An
additional dose is then recommended
around one hour before bed
• If the insomnia is not severe, then
the herbs can be taken as a single dose
before bed. Key herbs include Valerian,
Zizyphus, Hops, Passionflower, Kava,
Californian Poppy and Chamomile
Insomnia
Therapeutic Strategy: Goals, Actions and Herbs
• Best results with Valerian come from continuous
use for at least two weeks (unless in a synergistic
formulation with other herbs)
• Antidepressant and nervine tonic herbs
are indicated, especially if the insomnia
is associated with fibromyalgia or is
sleep maintenance insomnia. These
include St John's Wort, Skullcap and
Damiana
Insomnia
Therapeutic Strategy: Goals, Actions and Herbs
• If the patient is adrenally-depleted and suffers
from sleep maintenance insomnia then adrenal
tonics such as Licorice or Rehmannia
are indicated. These herbs will also
help maintain blood sugar levels
during the night
• Tonic and adaptogenic herbs used
throughout the day can help to break the vicious
cycle of non restorative sleep in stressed patients
• Withania can be a key herb for this
Insomnia
Therapeutic Strategy: Goals, Actions and Herbs
• If pain interferes with sleep then analgesic
herbs for pain management are indicated.
For example, Willow Bark is useful for pain
associated with inflammation, whereas
Corydalis, Cramp Bark, Kava and Wild
Yam will help to alleviate pain associated
with smooth muscle cramping
• Recent research with Chaste Tree
represents a new development in the
treatment of maintenance insomnia
Chaste Tree and Melatonin
Melatonin Release
According to Dioscorides
(De Materia Medica AD40 to 80)
when writing about Chaste Tree:
“A weight of 1 drachma in wine makes the menses
come on earlier, detaches the embryo, attracts the
milk, goes to your head and brings sleep.”
Upton R, Petrone C, Graff A (eds). American Herbal Pharmacopoeia, Santa Cruz, CA, 2001
Chaste Tree and Melatonin
Melatonin Release
• The circadian rhythm of melatonin
secretion was measured in 20 healthy
males aged 20 to 32 years after the
intake of placebo or various doses of
an extract of Chaste Tree for 14 days
• In an open, placebo-controlled study, the doses
investigated were 120 to 480 mg per day of this
extract (corresponding to approximately 0.6 to
2.4 g of dried berries, equivalent to 1-5 Chaste
Tree tablets)
• These were taken as divided doses at 8.00, 14.00
and 20.00 hours
Chaste Tree and Melatonin
Melatonin Release
• The concentration of melatonin in
serum showed the typical nocturnal
increase, beginning approximately
1 hour after the light was turned off
• Administration of Chaste Tree caused a
dose-dependent increase of melatonin secretion,
especially during the night (compared to placebo
treatment)
• Total melatonin output was approximately 60%
higher in the group receiving Chaste Tree
Dericks-Tan JS, Schwinn P, Hildt C. Experimental and Clinical Endocrinology & Diabetes 2003; 111: 4446
Chaste Tree and Melatonin
Melatonin Release
• The authors observed that the
feeling of fatigue or the promotion
of sleepiness observed by some
patients taking Chaste Tree during
the trial might be a result of the stimulation of
endogenous melatonin secretion
• Indications for Chaste Tree should now include
jet lag, maintenance insomnia, disturbed daynight rhythm (shift workers)
Insomnia
Example Herbal Liquid Formula
Sleep Onset Insomnia
Valerian
Passionflower
Zizyphus
Withania
1:2
1:2
1:2
1:2
25
20
25
30
100
mL
mL
mL
mL
mL
Dose: 5 mL with water 3 times per day or 8 mL twice
a day. Take the last dose one hour before bed. Also
consider Kava tablets before bed
Insomnia
Example Herbal Liquid Formula
Sleep Maintenance Insomnia
Valerian
St John's Wort
Chaste Tree
Skullcap
1:2
1:2
1:2
1:2
25
30
20
25
100
mL
mL
mL
mL
mL
Dose: 5 mL with water 3 times per day or 8 mL twice
a day. Take the last dose one hour before bed. Also
consider Kava tablets before bed.
Insomnia: Summary Protocols
Sleep Onset Insomnia
• Valerian or Kava, Passionflower, Zizyphus,
Corydalis, Chaste Tree
Sleep Maintenance Insomnia
• St John’s wort, Chaste Tree, Valerian
or Kava, Licorice and/or Rehmannia
Non-restorative Sleep
• Withania, Rhodiola or Korean Ginseng
Restless Leg Syndrome
Background Issues
• Restless legs syndrome (RLS) has been
described as “the most common disorder
you’ve never heard of”
• It is an unusual sensation (paraesthesia)
in the legs which typically occurs at bedtime
and is a common cause of insomnia
• The sensation has been described as uncomfortable,
not painful but more like “creepy crawly, tingling …”,
which is temporarily relieved by moving the legs
Clark MM. JABFP 2001; 14(5) 368-374
Restless Leg Syndrome
• Most people with RLS also move their legs once
they are asleep (including nocturnal myoclonus).
These movements can disrupt their sleep and
further add to the daytime drowsiness
which the syndrome causes
• With some people it can be so extreme
that it becomes like torture. They pace
the floor in the middle of the night, only
to have their symptoms return as soon
as they collapse, exhausted, back to bed
Clark MM. JABFP 2001; 14(5) 368-374
Restless Leg Syndrome
• RLS is surprisingly common. Various estimates
have ranged from 2% to 15% of the adult
population, with the real number likely to be about
6%.1 It is more common in women2
• The older you are, the more likely you are to suffer
from restless legs. It is rare in young children and
for those older than 65 years
around 10% to 28% are affected1
1.
2.
Clark MM. JABFP 2001; 14(5) 368-374
Ohayon MM, Roth T. J Psychosom Res 2002; 53(1): 547-554
Restless Leg Syndrome
• The cause of RLS is not known. It is known to be
associated with a number of medical conditions
• For example iron deficiency, even at levels which
do not cause anaemia, seems to predispose to
restless legs
• From 20% to 57% of people receiving kidney
dialysis are also affected1
1.
Clark MM. JABFP 2001; 14(5) 368-374
Restless Leg Syndrome
• The condition is much more common during
pregnancy.1 One survey of 500 women
found that 19% reported RLS during
pregnancy, that 7% described their
symptoms as “severe” and that the
condition abated in 96% of affected
women within one month of giving birth1
• Increased symptoms have also been associated
with decreased magnesium and folic acid1
1.
Clark MM. JABFP 2001; 14(5) 368-374
Restless Leg Syndrome
• Magnesium therapy (12.4 mmol/day = 301 mg/day)
has been shown to be beneficial1
• A number of lifestyle factors have been associated
with restless legs syndrome. These
include heavy smoking, advanced
age, obesity, hypertension, loud
snoring, use of antidepressant
drugs,2 diabetes and lack of exercise3
1.
2.
3.
Hornyak M, Voderholzer U, Hohagen F et al. Sleep 1998; 21(5): 501505
Ohayon MM, Roth T. J Psychosom Res 2002; 53(1): 547-554
Phillips B, Young T, Finn L et al. Arch Intern Med 2000; 160(14): 2137-2141
Restless Leg Syndrome
• So obviously the more healthy your lifestyle, the
less likely you are to suffer from this condition.
Intake of alcohol, nicotine and caffeine should be
minimised1
• Conventional medical treatment for RLS focuses on
drugs for the nervous system. Some of these
drugs are quite powerful and
dangerous and should be reserved
for more severe cases
1.
Clark MM. JABFP 2001; 14(5) 368-374
Restless Leg Syndrome
• They include opioid drugs such as apomorphine
and tramadol, the benzodiazepine drugs such as
clonazepam, drugs used to treat Parkinson’s
disease such as levodopa and even antiepileptic
drugs like valproic acid
• A study found that RLS was very common in people
with varicose veins (22% incidence).1 After
treatment for superficial varicose veins
(sclerotherapy or vein stripping), 98% reported an
immediate improvement in their restless legs
1. Kanter AH. Dermatol Surg 1995; 21(4): 328-332
Restless Leg Syndrome
• When the blood is not circulating
properly the walls of the deeper
veins can stretch resulting in
unpleasant sensations in the legs.
The sluggish circulation can cause
red blood cell aggregation which
can further add to the
paraesthesia and restless legs
• Flavonoids, which are found in
many herbs but notably in this context Ginkgo
biloba and Horsechestnut, have been found to be
beneficial for restless legs1
1.
Nicolaides AN. Angiology 2003; 54(Suppl 1): S33-S44
Restless Leg Syndrome
Therapeutic Strategy: Goals, Actions and Herbs
• Anxiolytic and hypnotic herbs such as Valerian, Kava
(especially), Skullcap and Passionflower to alleviate
the nervous system imbalance which is part of RLS
• Many of the factors involved in RLS (smoking,
pregnancy, obesity, age, diabetes) all point to an
involvement of the circulation. Hence venotonic
herbs such as Horsechestnut and
Butcher’s Broom and herbs which
enhance circulation such as Ginkgo
have a key (but often neglected)
role to play
Restless Leg Syndrome
Example Herbal Liquid Formula
Horsechestnut
Ginkgo std ext
Valerian
Skullcap
Butcher’s Broom
1:2
2:1
1:2
1:2
1:2
Dose 8 mL with water twice a day
20
20
20
20
20
100
mL
mL
mL
mL
mL
mL
Anxiety
Types of anxiety are:
• Panic disorder, which is
characterised by the
presence of recurrent and
unpredictable panic attacks
• Phobic disorders which involve marked and
persistent fear of objects or situations, exposure to
which results in anxiety, eg claustrophobia
Anxiety
Types of anxiety are:
• Generalised anxiety disorder where
the patient suffers persistent and
often unrealistic worry together
with symptoms such as muscle
tension, restlessness and disturbed
sleep
• Post-traumatic stress disorder which follows
extreme trauma such as a life-threatening event
Anxiety
Treatment Strategy: Goals, Actions and Herbs
• The calming or anxiolytic herbs
(sometimes referred to as herbal
sedatives) are the key part of any
herbal treatment. The main herbs
with this property are Valerian, Kava,
Passionflower and Hops. Note that
Hops is said to be contraindicated if
there is associated depression
• Other anxiolytic herbs include
Californian Poppy, Corydalis
(various species), and Zizyphus seeds
Anxiety
Treatment Strategy: Goals, Actions and Herbs
• The nervine tonic herbs also have a
role (these herbs are anxiolytic, but
also lift mood) in the treatment of
anxiety. They include St John’s Wort,
Vervain, Skullcap, Damiana and Bacopa
• Cramp Bark and Chamomile may be
useful for any visceral symptoms
associated with the anxiety
and Hawthorn can be prescribed
where there are cardiac symptoms
Anxiety
Treatment Strategy: Goals, Actions and Herbs
• Anxious patients stress their bodies and deplete their
adrenal reserves. This can create a vicious cycle.
Hence tonic and adaptogenic herbs may be required
especially Withania, since it has calming
properties
• Patients can be advised to add a few
drops of Lavender oil to a bath
for its calming effect
• Any associated sleep disturbance
should be treated with a separate
formula or tablet at night
Anxiety
Herbal Liquid Formula
St John’s Wort
Passionflower
Skullcap
Valerian
Cramp Bark
1:2
1:2
1:2
1:2
1:2
20
25
15
20
20
100
mL
mL
mL
mL
mL
mL
Dose: 5 mL with water 3 times per day or 8 mL twice
a day. Also consider Kava tablets
Conclusions
• There is a strong evidence base supporting the
gentle option of herbal treatments for anxiety and
insomnia
• Unlike conventional medications, herbs for anxiety
and insomnia do not impair cognitive function at
normal doses
• Herbal treatments for anxiety and insomnia need
to be adapted to the individual needs and
responses of the patient