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Pharmaceutical Manufacturing and Packing Sourcer
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There are times when many patients feel ill-equipped to manage their
stress – whether it stems from the economy, jobs, extreme weather, their
own health, or that of loved ones or pets. Over time, these events may
take deleterious tolls on the body; numerous studies link anxiety and
stress with cardiovascular disease, for example. Not only does stress
increase disease incidence, but it also heightens the risk of an adverse
cardiovascular event, such as a stroke or heart attack. Studies have
shown that the prevalence of anxiety is high – approximately 70-80%
among patients who have experienced an acute cardiac event, and 20-25%
among patients who have not (1).
The Diagnostic and Statistical
Manual of Mental Disorders discusses the various conditions within the
anxiety spectrum. Along this spectrum are panic attacks, phobias,
obsessive-compulsive disorder (OCD), post-traumatic stress disorder, and
generalised anxiety and its subsets. Anxiety is even more widespread
than depression and, in many cases, these two diagnoses go hand in hand
(2). Prior to any intervention, it is important to rule out organic
causes, such as hyperthyroidism, carcinoid syndrome, or
pheochromocytoma, as well as numerous others.
Anxiety can be
acute (generally speaking, this will refer to a period lasting from two
days to four weeks) or chronic (occurs more days than not for at least
six months). In the short term, moderate amounts of anxiety can be a
beneficial part of our existence – for example, alerting us to danger,
or even increasing our performance. But chronic or severe anxiety can
take over one’s life and interrupt daily activities, disturb sleep,
encourage poor dietary choices, lead to a reduction in exercise, and
restrict social interactions. This can lead to serious health concerns
and will often cause or amplify relationship issues (3-4).
Pathophysiology
Genetic
factors appear to predispose individuals to the development of
generalised anxiety disorder (GAD). Data from twin studies have been
inconsistent, but what has been observed is that the serotonin
transporter gene-linked polymorphic region SS genotype (short/short)
appears more common in patients with GAD (6). Another theory involves
the variations in two subtypes of the glutamic acid decarboxylase gene,
which may increase individual susceptibility to anxiety disorders (7).
On
the topic of genetics, methylenetetrahydrofolate reductase (MTHFR)
polymorphisms have clear links to mood, anxiety and personality
disorders. The MTHFR gene provides instructions for making the MTHFR
enzyme, which plays a role in processing amino acids, and is important
for a chemical reaction involving forms of the vitamin B folate (folic
acid or vitamin B9). Specifically, this enzyme converts
5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (8-9).
Neuroimaging
and other studies suggest the symptoms of GAD are accompanied by an
enhanced emotional responsiveness in fear-related brain circuits. A 2009
study using functional magnetic resonance imaging showed that patients
who had GAD showed greater anticipatory activity than healthy controls
in the bilateral dorsal amygdala (10).
Meanwhile, a higher than
average number of traumatic experiences and other undesirable life
events in childhood have also been found to increase prevalence of GAD
(11). GAD is more likely to occur in people with behavioural inhibition –
a tendency to be timid and shy in new situations (12). Furthermore,
anxiety is multifactorial and can stem from myriad causes, or a
combination of them. Besides the aforementioned pathological conditions,
caffeine, poor sleep habits, a bad diet, unique nutrient deficiencies,
lack of exercise and numerous other factors can all play a part (13,14).
Allopathic Approach
Conventionally, anxiety –
regardless of etiology or form – tends to be managed primarily with
anti-anxiety medications, antidepressants, sleeping medications and, at
times, counselling, cognitive behavioural therapy or mindfulness (15).
With respect to the latter, there is increasing evidence of the efficacy
of mindfulness-based stress reduction and other behavioural health and
mind-body techniques on anxiety.
More patients seem to be
looking into safer alternatives to medication. Natural does not
necessarily equate to safe, but evidence-based nutraceutical
interventions for anxiety disorders are available. Patients who do not
tolerate their current pharmaceutical medicines may consider nutritional
and herbal options. It can be difficult to define what is integrative
medicine, and what is conventional or allopathic medicine, especially as
once-unconventional therapies have become increasingly accepted. That
said, some therapies which may not be considered mainstream still have
some evidence of efficacy as adjunctive treatments – or as outright
substitutions – such as pharmaceuticals, although they may have
significant adverse effects. Some examples of such therapies, and their
dosing and important references, are listed below.
Ashwagandha
Withania somnifera (or ashwagandha) is an Ayurvedic that has anti-ageing, haematopoietic,
immune-modulating, anxiolytic, antidepressant, cardiovascular
protection, anti-tumour and antineoplastic properties. Recommended
dosage is 3,000-6,000mg of dried root or 300-500mg standardised extract
(16-18). In a 2012 study, 64 randomised test subjects were given either
ashwagandha or a placebo twice a day for 60 days. On day 60, a
significant reduction in stress scores and cortisol levels were observed
compared to the placebo (16).
Green Tea
L-theanine
(200-400mg daily) is an amino acid found in tea – with higher amounts in
green tea – that can reduce anxiety and increase levels of
gamma-aminobutyric acid (GABA) and serotonin (19-20). In 2011, an
eight-week randomised, double-blind, two-centre, placebo-controlled
trial aimed to discover if L-theanine would be effective at relieving
some of the symptoms of schizophrenic test subjects. The authors found
that the nutrient was a safe and well-tolerated augmentation of
antipsychotic therapy, which can “ameliorate positive, activation, and
anxiety symptoms in schizophrenia and schizoaffective disorder
patients”.
GABA
The regulating agent GABA (100-200mg
up to three times daily) can itself offer natural relaxant effects (21).
A 2006 study used electroencephalography-measured alpha waves on 13
subjects, who were given either water, L-theanine or GABA. After 60
minutes of administration, GABA significantly increased alpha waves and
decreased beta waves compared to water or L-theanine (22). In the second
part of the study, eight acrophobic subjects received either GABA or a
placebo. All subjects were asked to cross a suspended bridge, during
which immunoglobulin A (IgA) saliva levels were monitored. The placebo
group showed a marked decrease in their IgA levels, while the GABA
group's were significantly higher.
Inositol
The
pharmaceutical fluvoxamine is commonly used to treat depression and OCD.
However, evidence suggests that the vitamin-based alternative inositol
(12-18g per day) can provide equivalent or better results when compared
to fluvoxamine (23-24). In a double-blind, randomised controlled trial
(RCT), Palatnik et al found that the number of panic attacks in the inositol group reduced by an average of four episodes,
compared to 2.4 from fluvoxamine over a one-month period. Nausea and
tiredness were more common with fluvoxamine, whereas inositol was
well-tolerated (23).
Omega-3
Essential fatty acid
omega-3 has been shown to reduce inflammation and anxiety at 2,500mg
daily (25). In a 12- week, double-blind trial, 68 medical students had
blood drawn at baseline and under stressful conditions (before an exam).
Lipopolysaccharide (LPS), tumour necrosis factor alpha (TNF-α) and
interleukin 6 (IL-6) were measured. The subjects were given either
2,085mg eicosapentaenoic acid combined with 348mg docosahexaenoic acid,
or a placebo. While LPS and TNF-α decreased with the nutrient, IL-6 was
seen to increase, and secondary analyses that used the plasma n-6:n-3
ratio in the treatment group showed that decreasing n-6:n-3 ratios led
to lower anxiety. The authors concluded: “The reduction in anxiety
symptoms associated with n-3 supplementation provides the first evidence
that n-3 may have potential anxiolytic benefits for individuals without
an anxiety disorder diagnosis.”
Kava Kava
Piper methisticum (kava kava) can be given at 150-400mg in divided doses of standardised
extract (70% kavalactones) (26-27). A 2003 eight-week, double-blind RCT
involving 129 patients indicated that kava kava LI150 is well-tolerated,
and is as effective as buspirone and opipramol in the acute treatment
of outpatients with GAD (26). Due to concerns about hepatotoxicity, most
experts recommend monitoring liver enzymes at baseline and every six
months if using kava kava long term. It should be avoided in people with
pre-existing liver disease.
Passion Flower
Passiflora incarnata (passion flower) at 45 drops per day of a tincture (1:8 in 45% alcohol)
was found to be just as effective as anti-anxiety drug oxazepam (28). A
double-blind RCT involving 36 outpatients found passion flower extract
to be equivalent to oxazepam in GAD. The passion flower was well
tolerated, while the participants who took oxacepam experienced
significantly more problems relating to impairment of job performance (28).
Lavender Oil
Silexan
is a lavender oil capsule (80mg daily) used as an alternative to
benzodiazepines – a type of sedative (29). A 2010 multi-centre,
double-blind study looked into the efficacy of a sixweek intake of
silexan versus lorazepam. The primary target variable was the change in
the Hamilton Anxiety Rating Scale (HAM-A). The mean of the HAM-A total
score decreased clearly and to a similar extent in both groups. Silexan
showed no sedative effects and has no potential for drug abuse; it may,
therefore, be considered an alternative to benzodiazepines for GAD.
Rhodiola Rosea
The herb Rhodiola rosea (100-400mg daily), known for its adaptogenic properties, has been shown
to decrease anxiety and enable better adaptation to stress response
(30-31). However, it should be used with caution in patients with
bipolar disorder.
Adverse Effects
All
nutraceutical interventions have the potential to interact with
psychoactive pharmaceuticals – including additive effects with
anxiolytics – so concomitant use should either be avoided or actioned
cautiously. In addition, GABA and L-theanine may theoretically
potentiate antihypertensives, so close monitoring is advised (32-33).
Precautions
should be taken with certain conventional treatments, including
selective serotonin reuptake inhibitors, or serotonin and norepinephrine
reuptake inhibitors, which block reabsorption of the neurotransmitter
serotonin in the brain and block the absorption of the neurotransmitters
serotonin and norepinephrine in the brain, respectively (34-35).
Nutrients like tryptophan, 5-hydroxytryptophan and s-adenosylmethionine
can increase the amount of serotonin and, combined with the main
medication, may cause serotonin syndrome (SS) in susceptible people. SS
can range in severity from mild to life-threatening – although most
cases are of a low level – and will resolve with prompt recognition and
supportive care (36-38).
Anxiety Resolution
Successful
anxiety resolution appears to be based on a combination of relevant
medications – whether pharmaceutical or nutraceutical – along with
counselling and stress reduction techniques. The brilliance of
integrative medicine is that it takes the patient’s whole picture into
account, and can determine an individualised treatment plan and strategy
formed from the evidence-based treatment recommendations.
NoteThis
article originally appeared in the June 2014 issue of Integrative
Medicine Alert under the title 'Some dietary supplements for anxiety'.
Reprinted with permission from AHC Media LLC, Atlanta, GA. Visit:
www.ahcmedia.com
References
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Anxiety Disorders: Diagnostic and Statistical Manual of Mental
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21. Gamma-Aminobutyric Acid (GABA), Alt Med Review 12: pp274-279, 2007
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23. Palatnik A et al, Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder, J Clin Psychopharmacol 21: pp335-339, 2001
24. Benjamin J et al, Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder, Am J Psychiatry 152: pp1,084-1,086, 1995
25. Kiecolt-Glaser JK et al, Omega-3 supplementation lowers infl ammation and anxiety in medical students: A randomized controlled trial, Brain Behav Immun 25: pp1,725-1,734, 2011
26. Boerner RJ et al,
Kava-Kava extract LI 150 is as effective as opipramol and buspirone in
generalised anxiety disorder – an 8-week randomised, double-blind
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36. Sternbach H, The serotonin syndrome, Am J Psychiatry 148: pp705-713, 1991
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