HERBAL _ DIETARY SUPPLEMENTS FOR THE TREATMENT OF ANXIETY DISORDERS

							  HERBAL & DIETARY
SUPPLEMENTS FOR THE
TREATMENT OF ANXIETY
     DISORDERS

   LAURA JACULA, PGY-2
        BRUYERE
   American Family Physician, August 2007

   3 categories:
      herbal supplements,

      nutritional supplements,

      neurotransmitter and hormonal precursors
   Information on supplements that claim to
    be useful for anxiety disorders were
    obtained from several websites
   Medline was used to search for clinical
    trials guidelines and meta-analyses
                     NO EVIDENCE:
   HERBALS: Ashwanandha (Withania somnifera), Bach flower
    essences, bacopa, berocca, borage juice (starflower), bugleweed
    (Lycopus virginicus), catnip, chamomile, damiana, fennel,
    feverfew, ginkgo, ginseng, golden rod (Rhodiola rosea), gotu
    kola, hops, kanna, lemon balm, lemongrass leaves, licorice,
    meadowsweet, motherwort, mullein (Verbascum sinuatum),
    mulungu, noni (Morinda citriofolia), peppermint, pine bark extract,
    reishi (Ganoderma lucidum), Relora (magnolia/phellodendron),
    schisandra, scullcup (skullcap), verbena (blue vervain)
   NUTRITIONAL SUPPLEMENTS: Adrenal extracts, carbohydrate-
    rich diet, garum armoricum (great bluefish), ginger, L-theanine
    (green tea), macrobiotic diet, milk peptides, oats, perilla oil
    (perilla frutescens), vitamins B3, B6, B12, and C
   NEUROTRANSMITTER AND HORMONAL PRESCURSORS:
    Amino acids (L-phenylalanine/phenylalanine, L-arginine, L-lysine,
    L-glutamine, L-leucine), melatonin, pregnenolone,
    phytoestrogens (soy or Mexican yam), tyrosine, SAMe (S-
    adenosyl-L-methionine)
           SOME EVIDENCE:
   HERBAL SUPPLEMENTS: Kava, St. John’s
    Wort, Sympathyl (California Poppy, Hawthorn,
    elemental magnesium), Passionflower, Valerian

   NUTRIONAL SUPPLEMENTS: Inositol

   NEUROTRANSMITTER/HORMONAL
    PRECURSORS: 5-hydroxytryptophan (serotonin
    precursor)
     Clinical trials demonstrating
          non-effectiveness:

   HERBAL SUPPLEMENTS: Cannabis

   NUTRIONAL SUPPLMENTS: Omega-3 Fatty
    Acids (as adjunct for treatment-resistant OCD)
   Kava Kava (Piper methysticum) is one of the
     main anti-anxiety herbs. It has a very quick
    calming effect on the nervous system with an
    uplifting, euphoric feeling. It is also a muscle
relaxant and mild sedative. It is specific for anxiety,
  tension, stress, irritability and insomnia. Kava is
      very good for people whose mind races.
                      KAVA
   Meta-analyses for GAD: Cochrane review, 12
    RCTs, kava consistently better than placebo in
    producing small reductions in anxiety symptoms,
    safe taken from 1 to 24 weeks

   Few small RCTs lasting on average 4 weeks
    showed no significant effect - most studies with
    effect were at least 8 weeks
   Kava dramatically inhibits cytochrome P450
   Reversible skin rash and yellow tint to the skin
    with long term use
   Cases of liver toxicity, some requiring organ
    transplants
   ? Non-standard inclusion of kava plant’s bark
   Unclear if dosing, preexisting liver disease or
    combination with other medications were cause
   RCT showed liver toxicity rare, benefits outweigh
    risks, safety compares with other anti-anxiety
    meds (Toxicology Letter, 2001)
Health Canada's recall and advisory
 regarding Kava in August 2002:

   “Kava is found in a range of herbal and
    homeopathic preparations and may also be
    occasionally found in food. It is reportedly
    used for anxiety, nervousness, insomnia, pain
    and muscle tension. Health Canada and
    several foreign regulatory agencies have
    received reports associating the use of kava
    with serious liver dysfunction. Therefore, the
    use of kava products is considered to pose an
    unacceptable risk to health.”
  St. John’s Wort (Hypericum perforatum) is a
gentle sedative which also has a calming effect on
the nervous system with restorative properties as
  well. It is specific for mild depression, anxiety,
 tension and irritability. It works by increasing the
 level of neurotransmitters in the central nervous
     system such as serotonin and dopamine.
           ST JOHN’S WORT

   Only effective trial involved patients with
    somatoform disorder (placebo controlled RCT)
   Placebo controlled RCT for social phobia - no
    effect
   Placebo controlled RCT for OCD - no effect
    (more agitation with St. John’s Wort)
   Small uncontrolled study for OCD - significant
    reductions in Yale-Brown Obsessive Compulsive
    Score
                     VALERIAN




   RCT with valerian versus diazepam, double blind,
    placebo controlled - no difference between placebo and
    valerian or placebo and diazepam, too underpowered
    (24 patients total)
   Open trial with St. John’s wort and valerian - combination
    better than St. John’s wort alone
            OTHER HERBALS:
   SYMPATHYL (California Poppy, Hawthorn,
    magnesium): Placebo controlled RCT with GAD,
    statistically significant but small clinical effect
    (Hamilton Anxiety Scale Score)

   PASSIONFLOWER: RCT with oxazepam with
    GAD, no placebo, both groups equally positive
    effect, small study
NUTRITIONAL SUPPLEMENTS
INOSITOL (VITAMIN B8)
   RCT with placebo in panic disorder - panic
    attack frequency and intensity reduced
   RCT with SSRI (Luvox) in panic disorder- similar
    effect, but no placebo used
   RCT with placebo in OCD - reduced OCD
    symptoms but not anxiety
   RCT with placebo in OCD with SSRI - no
    additional benefit
  NEUROTRANSMITTER OR
  HORMONAL PRECURSORS
5-HYDROXYTRYPTOPHAN
 RCT in panic disorder, artificial panic inducing
  challenge, small trial, positive effect but unclear
  if would translate to real-world
 RCT in mixed anxiety disorders, placebo,
  clomipramine, no clinically significant effect
 Case reports on safety - eosinophilia-myalgia
  syndrome (?contaminated product)
                  SUMMARY
   Short term use of kava for mild to moderate
    anxiety disorders for pts not using alcohol or
    other meds metabolized by the liver BUT Health
    Canada Warnings…
   Inositol 12 to 18g per day for panic disorder or
    for OCD (but no evidence with SSRIs)
   Should not encourage St. John’s wort, valerian,
    Sympathyl, passionflower, or 5-
    hydroytryphtophan
QUESTIONS?
                REFERENCES
1.   Health Canada: www.hc-sc.gc.ca/ahc-
     asc/media/advisories-avis/_20003/20003_103-eng.php

2.   www.healthyplace.com/communities/anxiety/treatment/
     alternative_treatment.asp

3.   American Family Physician, Herbal and Dietary
     Supplements for the Treatment of Anxiety Disorders,
     August 15, 2007