Integrative management of chronic pain

Integrative Chronic pain summary

The following are my own notes on chronic non-cancer pain derived from extensive reading of the medical literature and my own experiences treating chronic pain patients. As with all posts on this web site, for general education only and does not constitute medical advice to either patients or practitioners. 

  1. Introduction
    1. In the US, chronic pain affects over 116 million people, more than the total affected by cardiovascular disease, diabetes and cancer combined.
    1. Acute pain serves us well as a warning sign of danger and potential (or actual) tissue damage. 
    1. Chronic pain has the vague definition of pain that has persisted beyond the time of healing. Chronic pain is often a maladaptive expression of learned hypervigilance: fear of pain leads to feed-forward loop generating more pain, culminating in self-sustaining central sensitization that can be difficult for the patient to escape.
    1. The biggest predictor of chronic pain is the emotional charge – high risk if depressed, anxious, past trauma. Can highly predict who will have chronic low back pain (CLBP) based on psychosocial factors.
    1. Stress-Appraisal-Coping Model: 
      1. We are wired for negativity bias as a survival mechanism, amplifying negative experiences.
      1. Negative appraisals of threat and loss lead to hypervigilance, fear and eventually depression.
      1.  Avoidance leads to deconditioning with less musculoskeletal adaptive capacity and increased irritability.
    1. Chronic pain becomes a disease in itself.
    1. Very isolating, with familial, vocational, social, and community disruption as well as adverse effects from the long-term use of analgesics, especially NSAIDs and opioids. 
    1. Stress, hopelessness, fatigue, depression, anxiety, decreased concentration, and sleep disturbances and chronic pain feed on each other.
    1. Even with the brain’s intrinsic negativity bias, with directed mindful attention, the brain can be rewired for positive valences such as joy and safety. Meditation, mindfulness and hypnosis, Tai chi — all of these types of therapies create neurologic fitness, just as physical exercise creates physical and cardiovascular system fitness. The neurological remodeling occurs because of will and focused attention, which need to be sustained and consistent.
    1. Chronic stress may fatigue adrenals, depressing cortisol and no longer suppressing inflammatory mediators. Chronic stress selectively increases the number and activation of microglia in certain stress-sensitive brain regions, which may play a role in visceral hyperalgesia.
    1. Only 36% of the population reports no Adverse Childhood Experiences (ACEs). Rates of self-reported histories of emotional, sexual, and physical abuse are 10.6 %, 20.7% and 28.3% respectively.
    1. The interconnectedness of the pain processing regions along with their affective and cognitive regions are more like an orchestra — the instruments are the same but what music they make together depends on:
      1. The composer (individual history and genetics)
      1. The musicians (physiology and health)
      1. The conductor (individual interpretation)
    1. Brain areas involved in pain and in mind-body integration practices such as meditation have strong overlap.
    1. Patients vary considerably in their self-efficacy and patients reporting higher levels of self-efficacy have lower levels of pain and lower levels of psychological distress and more positive medical outcomes.
    1. Improvements in self-efficacy are related to positive short- and long-term outcomes of pain coping skills training and educational self-help interventions. Integrative medicine offers a vast menu of arenas for supporting self-efficacy from mind-body approaches, to nutrition, to various exercises and ways of engaging conventional and alternative medicine systems.
    1. The challenge for the practitioner is to dismantle the fear of pain that keeps sufferers from pursuing therapies, and to ignite the patients’ trust in their intrinsic health that can be used to regain some quality of life. Hope needs to be rekindled, as the most important outcome of the early appointments. Then the engagement of the patient’s internal healing potential will provide the power for healing. After all, there is much health in a person, even if s/he is in pain.
    1. The goal is to remove obstacles to regaining health and to harness and support the unfathomable power of the body, mind, heart and spirit to heal.
  2. Non-pharmacologic treatment of chronic pain: Fortunately, there are many effective interventions: Stress & inflammation may be treated using mind-body, nutritional, and botanical modalities. Anatomic malalignment as a result of altered biomechanics (from trauma, compensation, overuse or deconditioning) may, over time, lead to physiologic dysfunction, including edema and inflammation. This somatic dysfunction may be treated using both exercise and manipulation.
    1. Reframing of painful stimuli allow patients to unlearn, manage, and even heal from chronic rheumatologic pain syndromes. Chronic pain is mainly central sensitization, though peripheral sensitization can also contribute to chronic pain. HURT DOES NOT NECESSARILY EQUAL HARM. Central sensitization means pain felt in the tissues is no longer being (primarily) generated by the tissues. Because the tissues are no longer the issue, it is not helpful for patients to seek a greater understanding of the diagnostic label they may have been given—like a patient learning all he or she can about fibromyalgia. Rather, it is more important for patients to gain an understanding of the presentation of their particular symptoms. Let go of trying to forcibly control pain: the more a patient expects and comes to hate his or her pain, the more he or she unwittingly participates in its continuance. Teach a pain patient to stop hating their pain, which includes wishing that it would go away. A full understanding of central sensitivity is thus a first step in reducing fear so that healthful movement strategies may be adopted. Mindful use of language – has powerful influence in both positive and inadvertent negative clinical outcomes.
    1. Specific modalities with efficacy supported by research:
      1. Mindfulness-Oriented Recovery Enhancement (MORE) 
        1. Combines Cognitive beharioral therapy (CBT), Mindfulness and positive psychology. MORE led to significant reductions in pain severity (= .014) and pain-related functional interference (= .002) that were maintained for 3 months following the end of the treatment groups. Although the magnitude of changes in pain severity was modest, participation in MORE reduced the impact of pain on daily functioning by nearly one quarter from pretreatment levels of impairment. Journal of Pain & Palliative Care Pharmacotherapy. 2014; 28:122 –129. DOI: 10.3109/15360288.2014.911791
      1. Biofeedback: effective for tension & migraine headache, muscular neck & back pain, chronic pelvic pain, proctalgia, neuropathic pain. 
        1. Headache: QEEG biofeedback or computer animated relaxation biofeedback
          1. SS anemia in children – biofeedback assisted relaxation
      1. Clinical hypnosis Patient can be taught self-hypnosis to support self-efficacy. (See: The Role of Suggestions in Hypnosis for Chronic Pain: A Review of the Literature. The open pain journal 3(1):39-51 2010 Dillworth T, Jensen MP; PMID: 21686037). Effective for many conditions, including:
        1. LBP, arthritis, TMJ, fibromyalgia
        1. Cancer pain, sickle cell disease
        1. Anticipatory anxiety during painful medical procedures, with anesthesia & surgery. 
        1. IBS: Gut-directed hypnotherapy 
      1. Guided imagery– often combined with other modalities.
        1. Pediatric chronic functional abdominal pain
        1. Can add music, Progressive muscular relaxation (PMR). Effective for cancer pain, others.
      1. Mindfulness based Stress reduction (MBSR) effective in wide variety of pain syndromes, including breast cancer pain, fibromyalgia
      1. Yoga shown effective for labor pain, cancer, functional abdominal pains, others
    1.  Somatic dysfunction treatment: crucial component of integrative pain management. Body has incredible ability to compensate for trauma, both physical and emotional, splints around the injured areas, often even after acute injury has healed. Adhesions inhibit normally fluid tissues from freely sliding over one another, creates layers of abnormal biomechanics, until finally, sometimes years later, the end of the body’s ability to compensate may be reached and pain results. Cells sense and respond to mechanical stress via mechanotransduction.  Biomechanical dysfunction may possibly lead to less-than-optimal cellular function. Correcting biomechanics can have far-reaching beneficial effects, including decreased pain, better postural alignment, improved autonomic function and tissue perfusion.
      1. Neuromuscular Medicine (NMM)
        1. Effective for LBP, headache (including migraine), Irritable bowel syndrome (IBS) and may be more cost-effective than allopathic tx.
      1. Chiropractic
        1. Effective LBP, headache
      1. Massage– may be relaxation or structural type, e.g. weekly
        1. Effective for LBP, knee osteoarthritis (OA)
        1. Small studies suggest efficacy for various chronic pelviperineal pains (such as vulvadynia and dyspareunia)
      1. Meditative movement therapies (MMT) of tai chi, qi gong and yoga
        1. Effective for fibromyalgia
        1. Helpful for various pain syndromes, e.g. back pain, rheumatoid arthritis, headaches/ migraine and other pain
        1. Prevention: yoga instructors have significantly less degenerative disc disease than the matched control group
        1. Tai Chi effective for LBP, possibly knee OA.
      1. Feldenkrais & Alexander technique
        1. Effective for LBP, neck, shoulder pain
      1. Acupuncture– attempts to correct blocked or deficient bioenergy or ‘chi’
        1. Much safer than many conventional pain treatments, such as NSAIDs.
        1. Difficult to study scientifically. Traditional empiric evidence of efficacy
      1. Physical Medicine and Rehabilitation (PM&R) – focuses on function
    1. Graded and progressive exposure to movement and exercise: ‘Movement is the medicine’. Healing from almost any physical pain syndrome is facilitated by movement (of course done carefully and appropriately). Reconditioning requires thoughtful planning and consistent, appropriate and skillful execution. Functional fitness evaluation & goal setting. Assess hobbies and leisure activities. Functionally specific movements and exercises are top priority, broken down into graded, stepwise progressions. Simplified example: walking before running Assess irritability:  low – able to withstand significant movement and exercise without a flare-up. High irritability – flares with only minimal movement or exercise. Progression plan: Once baseline fitness and irritability level established, plan the progression of the movement/exercise program. This involves juggling the variables of time, volume and intensity. Progress time first. If highly deconditioned & irritable patient, start with very low volume and intensity movements.  Example – patient with OA can sit and spin on a stationary bike for 5 minutes without flaring-up, plan to increase the time spent riding by 15 to 30 seconds per day. In a very short time your patient can be riding comfortably for a half hour or more, thus achieving his or her goals for increasing tissue fitness and pain reduction. Next increase repetitions (reps). Lastly increase intensity, e.g. weight or load. When increasing load, lower the repetitions of the exercise. Goal: Generally a rheumatologic patient can find a balance between these three variables that allows for 30 minutes of exercise per day, 3 to 5 times per week. Such a program should help with pain reduction while increasing their tissue fitness. 
    1. Healthy attitude towards pain during rehab: 
      1. Patience: in early stages of recovery even light movement or exercise is often painful, and therefore misunderstood by the patient as harmful. To that extent, the patient’s sensitized nervous system sets pain thresholds very low and does not accurately sense actual threats to tissue damage. 
      1. Pain spread is just a false signal: there are no segregated parts of the nervous system, so more and more of the neural network may begin to participate in a persistent pain experience. As a result, the patient may feel as if the pain is spreading to other body parts. Knowing this is very helpful in reducing fear, catastrophizing and hypervigilance. 
      1. Pain may worsen but still safe: a sensitized nervous system then is merely increasing its warning in a misguided effort to stay safe. It is often helpful to teach a patient to talk to his or her nervous system, saying things like “thanks for the warning, but I’m okay.” This is a primary form of reframing pain signals. 
      1. Accept pain unpredictability – due to the myriad ways thoughts, emotions and activities sum to create pain experiences. Don’t spend too much energy puzzling out the exact reasons why the pain is high on a given day. Often, there is no explicit explanation accessible to rational thought and they may draw false conclusions that end up further restricting their activity and worsening the pain. Teach them to allow the pain to arise and pass without strong emotion. Rather than feeling compelled to figure it out or heal it in the moment, learn to manage reactions to it. Over time, as one’s emotional reactivity decreases, so too will one’s overall sensitivity, and thus the unpredictability of the pain. Support from a physical therapist (PT) (or certified strength and conditioning coach) who understands pain from both the tissue and emotional perspectives is critical to guide pain patient through progressive movement and exercise. Cognitive behavioral therapy (CBT) to assist in reframing and emotional support. Social support: warmth, touch and positive social interactions activate oxytocin release. This hormone may have an anti-stress effect and increase pain threshold. Positive effects of social interactions also include lower levels of inflammatory cytokines and lowered stress reactivity.
    1. GI health & Nutrition. Normalizing GI function is essential in treating chronic pain. Often the pain patient is so fatigued or physically or emotionally limited that nutrition is less than optimal, with convenience foods that may have high glycemic index, be pro-inflammatory or nutrient poor as the primary source of food. Doing a thorough intake, diet history, and addressing nutrition with these patients is vital.
      1. GI Disrupting factors to address include stress, poor diet, antibiotics, corticosteroids, infections & parasites, food intolerances and allergies
      1. Stress from any cause, such as excess life demands, early abuse or chronic pain, can dramatically change the gastrointestinal environment, altering microbiota which are necessary for stressor-induced increases in circulating cytokines. Altered GI function may predispose to anxiety.
      1. Lipopolysaccharide found in the outer membrane of Gram-negative bacteria is a potent stimulator of immune (and therefore inflammatory) responses. The imbalance of gram negative bacteria has been linked to hyperalgesia as well as to sensitization of trigeminal sensory neurons
      1. Beneficial bacteria can displace potentially pathogenic bacteria, influence nutrient and vitamin production, help remove toxins and stimulate the gut associated lymphoid tissue (GALT).
      1. Correct dysbiosis of the gut microbiome in chronic pain patients, for example with a plant predominant whole foods diet and cultured foods (yoghurt, kefir, miso, etc.). At this time this remains a conceptually derived approach – clinical trials proving efficacy are not yet available.
    1. Encourage all chronic pain patients to quit tobacco use (smoking, vaping, chewing). Smokers have increased pain, worse function and increased risk of abusing prescribed opioids.
    1. Optimize ‘pillars of health’ – healthy eating, sleeping, exercise, stress management, relationships, spirituality in all chronic pain patients
    1. ‘Diabesity’ (visceral obesity and insulin resistance syndromes such as DM2) is associated with chronic pain, multiple aggravating comorbidities such as sleep apnea, depression, cognitive impairment, OA, CVD, etc.  A plant-predominant (at least ½ plate veggies of different colors) whole foods eating pattern and regular exercise are important in all chronic pain patients, but especially in these patients.
  3. Botanicals & supplements with at least preliminary research supporting efficacy in pain syndromes. Use these only under the guidance of a properly trained health care practitioner and please review proper use and cautions on all these from standard references such as Integrative medicine textbooks, Natural Medicine database, etc.):
    1. 5-hydroxytryptophan (5-HTP):
      1. Fibromyalgia & insomnia
      1.  Chronic headache
      1. Typical dose: 100 mg po TID or 300 mg qHS
    1. Ashwagandha (with other botanicals such as ginger, turmeric, boswellia): OA, RA.
      1. Typical dose of powdered root is 2-3 grams per day, or equivalent in tincture form. There are standardized extracts available containing 2.5% withanolides and taken at a dose of 500 mg 2-3 X/day
    1. Avocado soybean unsaponifiables (ASU) 1/3 avocado, 2/3 soybean oil ASU contains various compounds, including phytosterols, β-sterols, stigasterol and campestrol, and it may improve articular collagen synthesis while also serving as an anti-inflammatory.
      1. 3 studies show efficacy of ASU for knee and/or hip OA with less pain and swelling after 3-6 months of 300-600 milligrams of ASU daily, using the proprietary formula Piascledine®300. SEs seem rare, possible rash, GI upset, LFTs (causality unclear).
    1. Boswellia serata– inhibits the synthesis of the pro-inflammatory enzyme, 5-lipoxygenase, improves OA sx. Research supported brands:
      1. 5-Loxin®, 100-250 milligrams daily
      1. Alfapin® 50 mg BID
      1. Boswellia extract 333 milligrams three times daily
      1. SEs low
    1.  Butterbur (Petasites hybridus) – natural anti-histamine for allergic rhinitis and for migraine headache prophylaxis. Its use in migraines is likely due to smooth muscle relaxation and leukotriene inhibition
      1. a standardized butterbur extract (Petadolex®) 50-75 milligrams BID decreases # migraine attacks/month and decreased med use.
      1. CAUTION: A standardized extract (e.g. Petadolex) free of the hepatotoxic pyrrolizidine alkaloids must be used; whole plant butterbur should not be ingested.
    1. Cat’s claw (U. tomentosa and U. guianensis)
      1. Arthritis
        1. RA: Krallendorn (U. tomentosa root extract brand) 20 mg po TID decreased joint pain in DBRCT. Krallendorn is a patented brand name of IMMODAL Pharmaka GmbH and refers exclusively to the preparation containing a standardized extract from the root of the pentacyclic chemotype of Uncaria tomentosa.
        1. OA: freeze-dried preparation of U. guianensis bark 100 mg po daily
        1. Serious adverse effects are listed but likely rare, include GI upset, kidney failure, neuropathy, altered heartbeats, immunostimulation, hypotension, decreased estrogen and progesterone levels, and increased bleeding
        1. CAUTION: may inhibit the cytochrome P450 CYP3A4 enzyme
    1. Harpagophytum procumbens (Devil’s claw) standardized to 50-100 milligrams harpagoside daily which inhibits various inflammatory mediators via NF-kappa-B and COX-2 inhibition.
      1. Effective in arthritis – should provide 50 – 100 mg harpagosides/d
        1. Harpadol (Arkopharma) 1 – 2 caps (435 mg each) po TID (maximum dose of 2.6 grams/day provides a total of 57 mg of the harpagoside constituent and 87 mg of total iridoid glycosides. Each 435 mg capsule contains 2% harpagoside (9.5 mg per capsule) and 3% total iridoid glycosides (14.5 mg per capsule).
        1. Doloteffin, Ardeypharm) Dose: total of 2400 mg/day providing 60 mg/day of the harpagoside constituent.
      1. Other reputable brands:
        1. Nature’s Way Devil’s Claw: Take 1 tablet (480 mg) 2 -3X/d with food.
      1. Adverse effects mainly minor, GI upset
      1. CAUTION: Devil’s claw may increase stomach acidity, lower blood sugar, and interact with anti-coagulants and digoxin
    1. Feverfew (Tanacetum parthenium)
      1. Migraines: use C02 extract (MIG-99), dosed at 6.25 mg TID
      1. Adverse effects: GI upset
    1. Ginger (Zingiber officinale) rhizome contains numerous compounds that inhibit pro-inflammatory prostaglandins and leukotrienes.  Often combined with other botanicals such as turmeric, boswellia. Modest efficacy alone for:
      1. OA
      1. Dysmenorrhea
      1. Adverse effects uncommon. Mild GI upset.
      1. Extracts typically sold as anti-inflammatories are too potent for use during pregnancy
    1. Glucosamine and chondroitin
      1. Mixed evidence, recent major trial showed no benefit. GAIT trial found insignificant trends for improvement in joint pain with celecoxib 200 milligrams daily and glucosamine hydrochloride 1500 milligrams daily; and very little effect with chondroitin sulfate and the glucosamine-chondroitin combination
      1. Possible Glucosamine sulfate better than the HCl salt.
      1. Bioavailability of Glucosamine sulfate and Chondroitin sulfate may be improved by taking them separately as opposed to as a combination pill (preliminary evidence)
      1. Pharmaceutical grade formulations such as InvigoFlexD (distributed by WynnPharm) may be more efficacious
    1. MSM(Methylsulfoylmethane) is found naturally in veggies & fruits, sulfur moiety may scavenge free radicals, thus decreasing inflammation.
      1. 1 RCT shows less pain in knee OA.
      1. Adverse effects minimal
    1. Magnesium– Deficiency alters neurotransmitter release, hyper-aggregates platelets, vasoconstricts, activates NMDA receptor with resultant glutamate release into the synapse. Mg blocks spreading cortical depression induced by glutamate. Stress reduces Mg availability.
      1. Migraines, especially menstrual migraines: 2 double blind randomized controlled trials (DBRCTs) show 600 mg/d Mg decreased frequency of migraines (1 other trial was negative). Intracellular Mg low in ½ of women with menstrual migraine attacks, even if serum Mg is normal.
      1. Dose typically 600 mg/d, can increase to 1 G/d. Use Mg chelates or Slo-Mg
        1. IV MgSO4 1 gram can terminate migraine with aura or if low ionized Mg
      1. Adverse effects: diarrhea is rate-limiting SE.
      1. CAUTION in poor renal function
    1. Omega 3 fatty acids.  EPA and DHA compete with dietary or n-6-derived arachidonic acid as substrates for metabolism by cyclo-oxygenase and lipoxygenase enzymes. Arachidonic acid leads to the formation of series 2 prostaglandins (PGs), series 4 leukotrienes (LTs), and thromboxane A2, all of which are pro-inflammatory in the human body, while n-3 fatty acids lead to the formation of series 3 PGs, series 5 LTs, and thromboxane A3, which are less inflammatory, probably accounting for the benefits of omega-3s in arthritis
      1. RA – reduces joint inflammation and med use.
      1. Dose: EPA 2 – 4 G, DHA 1-3 G
      1. Adverse effects low. Freeze capsules to lessen fishy burp.
    1. S-adenosylmethionine (SAMe) used in supraphysiologic doses for pain associated with fibromyalgia and osteoarthritis. Broad physiological effects, including centrally-acting changes in neurotransmitter concentrations
      1. Fibromyalgia
      1. OA
      1. Dose for above typically 200 – 600 mg/day
      1. Adverse effects generally mild & self-limiting: GI upset. (Note: higher doses used for depression are contraindicated in bipolar because of concerns might induce mania)
    1. Baikal, or Chinese, skullcap (Scutellaria baicalensis/barbata)
    1. Turmeric (Curcuma longa) contains curcuminoids, one of the principal being curcumin, which has been shown to inhibit numerous inflammatory mediators.
      1. RA – 1200 milligrams of curcumin daily decreases inflammation and improves walking time. In 1 trial 500 mg curcumin po daily improved Disease Activity Score (DAS) more than diclofenac.
      1. OA – propriety curcumin/phosphatidylcholine extract (Meriva, Indena SpA) at doses of 200 mg per day the global WOMAC score decreased by 58% (P<0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), and CRP levels decreased from 168 ± 18 to 11.3 ± 4.1 mg/L in the subpopulation with high CRP when compared to the control group (Belcaro 2010).
      1. 1 trial turmeric extract (from Curcurma domestica) 500 milligrams of curcuminoids four times daily helped to control knee arthritis pain as well as 400 mg twice daily of ibuprofen
      1. Adverse effects minimal:      GI upset
      1. Note: needs to be complexed with phosphatidylcholine or piperine from black pepper to have adequate bioavailability.
    1. Willow (Salix alba, or white willow) contains several glycosides (salicin, salicortin, fragilin, and tremulacin) and the primarily metabolite, salicylic acid, that act as nonselective COX-1/COX-2 inhibitors
      1. LBP – 120-240 mg salicin daily
      1. Note: Estimates are that 240 milligrams of salicin is equivalent to 50 milligrams of ASA, leading most experts to consider Salix alba as an adjunctive therapy for pain, at best.
      1. Adverse effects: GI distress
    1. Cannabis and derivatives?  Many different cannabinoids, some with relaxant properties. Research is preliminary.
    1. Topicals:
      1. Capsaicin cream or patches.
        1. OA e.g. knees, hands: Modest benefit with creams containing 0.025%- 0.075% capsaicin applied 3-4 times daily – adjunctive tx.
        1. For neuropathic pain, the 0.075% cream helps
        1. PHN: a single, 60-minute application of 8% capsaicin patches (Qutenza) provides up to three months relief from pain associated with post-herpetic neuralgia (PHN).  Can try off label for HIV-related neuropathy and other cases of peripheral neuropathy.
        1. CAUTION: always use gloves when applying. Local cooling or oral analgesics if burning is an issue. Don’t touch eyes, genitals or other sensitive tissues after applying!
  4. Other botanical uses
    1. Nervines can help with sleep and anxiety in chronic pain: Valerian, Passionflower, hops, Chamomile
    1. Oral mucositis, lichen planus responds to chamomile
    1. Rhodiola helps fatigue, some mood elevating effects. May be good for fibromyalgia
    1. Migraines– use Petadolex (Butterbur) LOE A & Magnesium
    1. Curcumin at sufficient dose (e.g. 1500 mg/day) has analgesic benefit
  5. Pharmacologic: Often as a treatment program begins, immediate pain control is needed to ease suffering and to allow the patient enough relief and free sufficient psychic (emotional) energy to devote him/herself to the usually more labor-intensive integrative approaches. And sometimes, integrative approaches cannot resolve chronic pain completely, so some medication may be needed long term. Below are some brief comments. Please reference standard resources for full information on proper use. 
    1. Acetaminophen: max. officially 4 G/d but in chronically ill such as many pain patients consider max. 3 G/d. Consider adding N-acetylcysteine (NAC) if higher range and liver risk.
    1. NSAIDs: Topical NSAIDs are best when used for acute musculoskeletal pain. Because of the route of administration, there are localized effects and no gastrointestinal concerns. Avoid long term use of systemic NSAIDs as first line chronic tx whenever possible. The main adverse effects are inhibition of platelets, gastrointestinal injury, hypertension, renal injury and increased risk cardiovascular events.
      1. Do prevent platelet inhibition by aspirin in vitro (therefore consider avoiding e.g. if h/o CAD on ASA): ibuprofen, naproxen, nimesulide, oxaprozin, piroxicam, flufenamic acid, dipyrone and celecoxib
      1. Do not prevent platelet inhibition by aspirin in vitro: diclofenac, ketorolac and ketoprofen. 
      1. Sometimes if one class of NSAID doesn’t work well, switching to another class works better:
        1. Salicylates: Aspirin, Diflunisal, Salsalate
        1. Acetic acid derivatives: Diclofenac, Etodolac, Indomethacin, Ketorolac, Nabumetone, Sulindac, Tolmetin
        1. Enolic acid (Oxicam) derivatives, Meloxicam, Piroxicam
        1. Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Fenoprofen: Flurbiprofen, Oxaprozin
        1. Anthranilic acid derivatives (Fenamates): Mefenamic acid:
Selective COX-2 inhibitors (Coxibs): Celecoxib
    • Tramadol
      • Weak activity at mu (opioid) receptors and also has some inhibition of serotonin and norepinephrine uptake. Similar side effect profile to mild opioids but has been shown to relieve both neuropathic pain (Duhmke, 2004) as well as fibromyalgia.
      • Potentially habit forming like opioids, therefore use with caution
      • Decrease the seizure threshold especially with neuroleptics and antidepressants. Caution if co-morbid psych.
    • Opioids
      • Background:
        • Endogenous opioid system normal functions include stress-induced analgesia, social affiliation/bonding including maternal-infant bonding, rewards for natural pleasures such as sex and eating. Opioids often used as a substitute for social connection.
          • Emotional pain such as social rejection has similar neurobiology to physical pain on fMRI, etc.
      • Very effective for acute severe pain.
      • Chronic pain is not very satisfactorily managed with opioids because of peripheral and central sensitization. 
      • Problems with opioids: Chronic opioids (especially morphine & fentanyl) lead to tolerance and may lead to opioid induced hyperalgesia (OIH). OIH is apparently uncommon & a dx of exclusion, but some pain specialists believe is very common. Hypothetical mechanisms of OIH: activation of spinal dynorphin, bradykinin receptor, toll-like receptor-4 on glial cells, resulting in a pro-inflammatory state that manifests clinically as increased pain. Opioid-overuse headache is a phenomenon similar to opioid-induced hyperalgesia, which derives from a cumulative interaction between central sensitization, due to repeated activation of nociceptive pathways by recurrent headaches, and pain facilitation due to glial activation. Hypogonadism is especially common in chronic long-acting opioid use. Chronic opioids associated with multiple other adverse effects including increase MI.
      • OIH tx strategies: wean down analgesics. Clonidine, buprenorphine. Early studies that curcumin may benefit (UI: 23273833).
      • Issues with opioids:
        • Research sparse and does not support long-term efficacy, but strongly documents harm.
          • Long-term opioid therapy is associated with lower rates of recovery from chronic pain and return to work.
          • Aversive selection– patients at highest risk of misuse such as h/o psych & substance abuse disorders are most likely to be prescribed high risk long term opiates
          • Lots of diagnoses that don’t necessarily correlate with a patient’s pain. For example, a patient may have documented disc bulges and degenerative disc disease on x-ray/MRI, but the actual main driver of their pain is para-lumbar myofascial dysfunction with poor eating and gut dysbiosis, sedentary habits with deconditioning and disturbed mood and sleep habits and high stress all leading to central sensitization. Doctor’s visits are short and careful psychological and lifestyle evaluation is often minimized. Patients get attached to their diagnoses such as ‘arthritic spine’ and come to believe the locus of control for healing their pain is external-a pill or procedure – and out of their control, leading to low self-efficacy. 
          • Dramatic increase in misuse/abuse/deaths with increased prescription of opiates, which is proportional to mainly length of use but also dose of opiates – odds ratio for misuse/abuse increases >100X in high dose chronic opioid use! Most heroin addicts started their habit with a prescription opioid.
          • Immunosuppression
          • Brain inflammation: glial cells that surround neurons produce inflammatory cytokines, will react to trauma with an inflammatory state in their neocortex which may predispose to psychological disorders such as depression and anxiety. Opioids may aggravate this.
          • Opiate use associated with double fractures incidence in > 60 y/o.
          • Maternal use associated with neonatal abstinence syndrome, low birth weight
          • Monitoring of opioid use:
            • Use ‘Comprehensive urine drug screen’ and follow CDC and state guidelines
    • Anti-epileptics
      • Gabapentin
      • Pregabalin
      • Carbamazepine
    • Neurohormone reuptake inhibitors
      • TCAs
        • Amitriptyline: strong anti-cholinergic effects. Start at 10 mg qHS and slowly titrate as needed
      • SNRIs
        • Duloxetine
        • Venlafaxine
    • Muscle relaxants
      • Cyclobenzaprine
    • Addiction opioids
      • Methadone – can prolong QT – monitor EKG
      • Buprenorphine (requires special certification to prescribe for addiction, but NOT for general treatment)
    • Topicals
      • Lidocaine patch
      • Capsaicin
      • NSAID topicals
    • Compounded mixtures, e.g. gabapentin, ketoprofen, ketamine, amitriptyline
  • Summary on Integrative chronic pain treatment:
    • Highly recommend Integrative Medicine pain specialist consultation for all chronic pain patients
    • Pain specialists invaluable for specific pain generator issues, e.g. epidural for discogenic CLBP and to guide/take over if need high dose opioid pain meds
    • Palliative care specialists also invaluable for many non-curable pain situations
    • Minimum 30 minute visit
    • Gather a team
    • Nutrition consult in all chronic pain patients. Assess and correct dysbiosis.
    • Consult movement specialists, especially mind-body integration experts, e.g. Tai Chi, Yoga teachers
    • Mindfulness based programs should be core in chronic pain treatment protocols. Encourage daily meditation in all chronic pain patients.
    • Treat using chronic opioids like using chronic steroids – only with great caution and if clear, robust benefits compared to risks
  • Further questions to be explored:Do chronic opioids lead to dysfunction, atrophy of or even damage to the endogenous pain control mechanism, similar to how corticosteroids lead to secondary adrenal insufficiency?How common is opioid induced hyperalgesia, and what are factors increasing the risk?
  • Special situations and conditionsComplex Regional Pain Syndrome (CRPS)– potentially devastating and difficult-to-treat chronic neurological pain syndrome that arises from an abnormal response to an often innocuous injury. Prolonged versions of the normal injury response. Most cases however, are not diagnosed for years. Though may resolve, sometimes the pain is so severe that lives are destroyed, and suicides are not uncommon. Primary care physicians often miss it. Type 1 is RSD; Type 2 is causalgia after a nerve injury.Key questions to pick up CRPS:Is the breeze from the heat/ air conditioning/ fan intolerable?Does the weight of a bed sheet bother your foot/ leg/ arm/ hand?Does the arm/ hand/ leg/ foot have severe, constant, burning and/or deep aching pain?Is there a prolonged after-sensation of pain (hyperpathia)?If the answer to any of these is ‘yes,’ and the pain has been there for less than 3 – 6 months, immediately start aggressive treatment: double dose Medrol dose pack, PT including desensitization, and mirror therapy, analgesics. Once the ‘grace period’ is over, CRPS signs and symptoms include:Skin, hair and nail changesVasomotor and sudomotor changesSwellingSensory changesAbnormalities in X-ray (patchy osteoporosis) and triple phase bone scansBiomechanical and movement abnormalitiesSpreading of the pain, either in the same limb, to the opposite limb, or anywhere in the bodyIf not treated in the first 3 months, the changes can rapidly render this a decades-long pain syndrome.  Can try Serotonin norepinephrine reuptake inhibitors (SNRIs), Pregabalin, gabapentin, Tricyclic anti-depressants (TCAs), topical Lidocaine, opioids, tramadol, baclofen, amantadine 100 mg BID, ketamine. Refer to specialist who does interventional procedures such as stellate ganglion blocks may be appropriate. Barriers to the healing of nerves and blood vessels, including tobacco use, excess alcohol, hyperglycemia or diabetes, cardiovascular impediments, malnutrition, and subclinical polyneuropathy, may require treatment.
    • Good resources for patients:
      • Butler, D. and Moseley L., Explain Pain, NIO Group Publications, 2003. An evidence-based book written for the purpose of teaching patients the nature and better management of chronic pain.
      • Melzack, R. and P.D. Wall, The Challenge of Pain, 2nd ed., London: Penguin. 1996. Another fantastic book written for the public on the nature of pain.
      • Nicholas, M., et al., Manage Your Pain. Sydney: ABC Books. 2000. This is a self-help book written by the pain management team at Royal North Shore Hospital in Sydney, Australia.
      • Sopolsky, R. M., Why Zebras Don’t Get Ulcers: An Updated Guide to Stress, Stress Related Diseases, and Coping. A still timely classic. New York: W.H. Freeman and Co. 1998.
  • Abbreviations: CLBP = Chronic low back pain, LBP = Low back pain, SS = Sickle cell disease, RA = Rheumatoid arthritis, Tx = treatment

Integrative approach to headache

Notes on An integrative approach to Headaches


This represents my personal approach – Dr. Remde. Please double check all therapeutics with other resources.

As with all documents on this website, does not represent medical advice. For general education only.



  • Overview
  • Tension-type and migraine headache 2nd & 3rd most prevalent disorders in the world. Migraines in 10% of population, Female: Male ratio is about 3:1. Major impact on quality of life and lost work days. 50 % Migraines under diagnosed! Directly ask if problems with headaches, because patients often don’t talk to their physicians about them.
  • Red flags/Increased surveillance:
  • First or worst
  • Abrupt new headache
  • >50 yrs.
  • Abnormal exam
  • Unstable pattern
  • Systemic illness
  • H/o cancer or immunosuppressed
  • New onset bad headache and pregnant (r/o venous thrombosis.)
    1. Secondary headaches:
      1. Subarachnoid hemorrhage (SAH) (CT misses early sentinel bleed 25 % of time – need to do LP to rule out).
      2. Meningitis (infectious on non-infectious) Fever + headache as PRIMARY complaint = R/O MENINGITIS
      3. Abnormal Intracranial pressure (ICP) (Too high or too low)
      4. Intracranial hematoma. Epidural bleed typically has a lucent interval.
      5. Tumor (rare for tumor to present SOLEY with headache with no other alarm symptoms or other physical exam  (PE) findings)
      6. Abscess
      7. Other
      8. Differential Diagnosis (Ddx) of Thunderclap headache:
        1. Aneurysmal rupture (or occasionally expansion, thrombosis, vasospasm)
        2. Cerebral sinus thrombosis (watch for in pro-thrombotic patients)
        3. Acute intracranial hypotension/CSF oligemia or leak, e.g. from dural leak (MRI w/ gadolinium will show meninges light up)
        4. Sexual headache, explosive type: indomethacin is Drug of choice (DOC).
        5. Crash migraine-(an unusual form of migraine that’s severity is maximal at onset)
      9. If eye pain is caused by eye dis, almost always eye LOOKS ABNORMAL to your naked eye. If not, it usually is neurologic cause, especially if eye signs
    2. Risk factors for secondary headache:
      2. Acute onset
      3. >55
      4. Occipital-nuchal location
    3. Neuroimaging: Any of above need imaging, e.g. MRI. Headache + blood thinner = brain imaging.
  • Migraines
      1. Overview: many often not formally diagnosed, patients often rely on Over the counter (OTC) for acute treatment.
      2. Genetic susceptibility: Migraine patient’s brains demonstrate hypersensitivity to visual, olfactory and auditory stimulation, and become more sensitive with repeated stimulation leading to allodynia, with slower than normal recovery from insults. A migraine is a genetically determined neurologic disorder of which headache is an intermittent expression. The nervous system is extra sensitive in migraine suffers – even when no headache is happening:
      3. Comorbid conditions: Depression/Anxiety, Insomnia, Irritable bowel syndrome (IBS), Fibromyalgia, Raynaud’s, Premenstrual syndrome (PMS), Essential tremor, Epilepsy, Stroke (slight increase incidence), Sensitivity to Medications!!
      4. Risk factors:
        1. F > M
        2. Obesity
        3. Low socioeconomic level
        4. Chronically exposed to stress, sleep deprivation, and poor self-care practices. 1/3 female medical students have migraines
        5. Child maltreatment strongly associated with migraines, with associated depression, anxiety, chronic illness, chronic pain IBS, chronic fatigue syndrome, and arthritis.
      5. Pathophysiology: ‘Migraine generator’ is in the serotonin-rich nuclei in the posterior midstem. Serotonin acts as a brake. The ‘engine’ is likely dopaminergic hypersensitivity which mediates prodromal migraine symptoms (as opposed to aura) including malaise, nausea, yawning, food cravings, irritability and motion sensitivity and triggers cortical spreading depression which, in turn, results in decreased cerebral blood flow. The cortical spread of slow waves from occiput is the cause of aura, which last < 60 minutes. Initial vasoconstriction is followed by vasodilation and sterile inflammation of meningeal vessels and pain. The vasoconstriction plays little, if any, role in the pathophysiology of migraine (including the increased risk of stroke).
      6. Mechanism of action of pharmaceuticals:
        1. Anti-migraine medications block cortical spreading depression (CCBs, anti-convulsants) or stimulate inhibitory serotonin receptors (Triptans), reducing pro-inflammatory neuropeptides in the afferent trigeminal pathway.
        2. Menstrual migraines: falling levels of progesterone lead to dopaminergic hypersensitivity, destabilizing the trigeminovascular system and resulting in a migraine attack. Dopamine blocking drugs include anti-emetics and phenothiazines, which may reduce both the pain and the nausea of migraine.
        3. Calcitonin Gene Related Peptide (CGRP) produced by both central and peripheral neurons plays a key role in the trigeminovascular system. CGRP monoclonal antibodies improve migraine frequency and severity, sometimes with prolonged remission (Schulte, 2015 doi: 10.1016/S1474-4422(14)70295-9).
      7. Migraines & hormonal effects: ~ 60% of F migraineurs have menstrual migraines.
        1. Estrogen “withdrawal” in the late luteal phase can trigger migraine. Ovarian hormones affect inflammation, affective states, stress responses, and pain reactivity. Estrogen and progesterone have potent effects on central serotonin, norepinephrine and opioid neurons, modulating both neuronal activity and receptor density.
        2. OCPs increase RR 10X for new onset migraines. OCPs increase frequency migraines during placebo week and increase stroke risk. WHO states OCPs absolute contraindication if migraine with aura, others make relative contraindication. For women desiring OCPs who have migraine with simple visual aura and no other stroke risks (e.g., smoking) choose ethinylestradiol (EE) < 35 mcg and drospirenone (DRS) which has less migraine risk. Otherwise, use (IUD), progestin based, or barrier forms of contraception. Close follow-up to monitor the headache pattern is crucial to pick up new onset aura symptoms or changes in cardiovascular risk status. The OC should be discontinued if migraines worsen after the first few months of treatment or if she develops aura.
        3. Perimenopausal woman with migraines may benefit from non-oral route, low dose HRT if no contraindications. Transdermal estradiol patch or gel can be used during the “placebo” week or 1-2 days before the onset of menses to prevent a rapid decline in serum estradiol. The dose is typically 100 mcg estradiol patch. If contraindications to HRT, consider venlafaxine, fluoxetine, or paroxetine for control of hot flashes and migraines.
  • Children and migraines
    1. Reported as young as 18 months old. Prevalence equal pre-pubertal. Half of all migraine sufferers will have their first attack before the age of 12, leading to school absences. Migraine often goes undiagnosed in children, as the headache is generally less severe, shorter duration may be bilateral and migraine equivalents may predominate such as unexplained N/V, abdominal pain, or dizziness. Motion sickness is an early warning of predisposition to migraine.
  • Triggers:
  • Triggers are highly individualized and often multiple.
  • 97% named at least one food trigger Perceived migraine triggers: do dietary factors play a role?. Camboim Rockett F; Castro K; Rossoni de Oliveira V; da Silveira Perla A; Fagundes Chaves ML; Schweigert Perry ID. Nutricion Hospitalaria. 27(2):483-9, 2012 Mar-Apr. . Research Support, Non-U.S. Gov’t] UI: 22732972
      1. Most common: “emotional stress” (59%), “too much or little sleep” (53.5%), “odors” (46.5%), and “missing meals” (39%).
      2. “Let-down headache” after a stressful period common
      3. Caffeine withdrawal important nutritional precipitating factors of both migraine and tension type headache, and there is also evidence that missing meals and dehydration can trigger migraines. May be stress rather than alcohol per se that is the trigger. Chocolate not a trigger in controlled trials.

Clinical presentation & Dx: Mild tension headache is common & these people usually don’t seek medical attention, BUT severe ‘tension headache’ is almost always part of migraine continuum & rarely exists as a sole type of headache. Episodic and chronic disabling headache is usually migraine. Under diagnosed in 60% F & 70% M! Most prevalent young and middle-aged adults, declines after 50 y/o

International Headache Society (IHS) Criteria

    1. : Any 2 of:
    1. 1. Unilateral
    1. 2. Throbbing
    1. 3. Worse w activity
    1. 4. Moderate or severe
    1. + any 1 of following:
    1. +N/V
    1. +Sense – phobia
      1. Do NOT have to have GI SE’s, Unilaterality, Pulsation
      2. OFTEN triggered by weather changes.
      3. MAY have runny nose, congestion, & ‘sinus ache’ are common part of migraine.
      5. 60% prodrome & 90% during headache have neck pain!
      6. 10% have aura: slow onset, disappears usually after 15-30′, occasionally up to 60’, moves across cortex 2mm/min as cortical spreading depression.
        1. Aura’s should have:
          1. Positive component, e.g.  ‘bright lights’
          2. Negative component, e.g.  ‘blind spots
          3. Dynamic component, e.g.  ‘shrinking or expanding’
      7. Arteriovenous malformations (AVMs) are linked to migraine and a migrainous aura may be the only clinical manifestation of an AVM before it bleeds. AVMs in the occipital, parietal, and temporal lobes are most likely to present with aura-type symptoms. Late age of onset of symptoms, complicated auras, absence of typical angular, scintillating features of migraine visual aura, unusual neurologic symptoms including seizures and coma, and headache that starts before rather than after aura may all be warning signs. An epileptic aura can be difficult to differentiate but may include changes in awareness, positive motor phenomena or automatisms. Multiple discrete aura attacks occurring within a single day, even with associated migraine headache, may suggest an underlying coagulopathy.
      8. PIN’: Answering ‘yes’ to 2 questions has sensitivity & specificity of ~ 75%:
        1. Photophobia: Does light bother you when you have a headache?
        2. Impairment: Has a headache limited your activities for a day or more in the last 3 months?
        3. Nausea? Are you nauseated or sick to your stomach when you have a headache?
  1. Chronic Daily headache = medication overuse headache (MOH) until proven otherwise. Can occur with ANY analgesic. 1-2% of headache sufferers. The intrinsic pain reaction system fails in the setting of chronic analgesics.
      1. Co-morbidities such as depression, anxiety, and sleep disturbances are common. It usually, but not invariably, resolves after the overuse is stopped. Migraine transformation: Episodic–> Tension–> Mixed–> Chronic daily headache (this would NOT have N/V, Photophobia, etc.)
      2. Key Point: Cutaneous allodynia strongly associated with chronic migraine and the risk for progression from episodic migraine to chronic migraine. Medications with a high risk for inducing medication overuse headache such as caffeine, butalbital and opioids should be used with extreme caution if at all.
  • Migraine tx


      1. Quality of life worse than CHF, O/A.
      2. Try average of 5 different options before find effective tx.
      3. Stratified care better:
        1. Tx matched to migraine severity/level of disability
        2. Tx early
        3. Change tx as needed
        4. Tx triggers: Smoking, fumes. Allergies – Astelin good for these acutely. Food
      4. Key is to remove fear of the next migraine
  1. Natural treatment:
      1. Pillars of health. Keep regular habits. Healthy wt. loss helps reduce migraine in the obese
      2. Mind/body modalities first line, LOE A, such as CBT, relaxation, thermal & EMG biofeedback. Help patient adapt to ‘sensitive nervous system’ and higher stress responses. Options include yoga, meditation, MBSR, hypnosis, others
      3. Acupuncture well supported for acute and prophylaxis migraines. At least as effective and possibly more effective than medication prophylaxis. Generally twice a week for at least 10 sessions. Cochrane 2009
      4. Physical modalities:
        1. Ice massage neck
      5. Supplements:
        1. Magnesium deficiency may be important in pathogenesis of migraine headaches, by promoting cortical spreading depression (CSD), alteration of neurotransmitter release, hyperaggregation of platelets and vasoconstriction (Review by Sun-Edelstein, 2009 doi: 10.1097/AJP.0b013e31819a6f65) (LOE B) ‘Strong recommendation’ by Canadian Headache Society (CHS).
          1. Dose: Magnesium glycinate or chelate e.g. 600 – 800 mg/day in divided doses or take one dose HS. Especially helpful in menstrual migraine, pediatric migraine/tension headache. Safe in pregnancy.
        2. Riboflavin – may help mitochondrial dysfunction, energy production. Deficiency can occur in pregnancy, infancy, and the elderly. Sx include light sensitivity. Powers, 2003, PMID: 22683887). Evidence mixed. (strongly recommended by CHS (Pringsheim, 2012, Canadian Headache Society guideline for migraine prophylaxis, Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1-59), ‘B’ recommendation by American Academy of Neurology (AAN) (Holland, 2012)
          1. Dose 4 100mg. tabs/d
        3. CoQ10: may benefit if mitochondrial dysfunction. RCT of 42 patients found 100 mg TID of CoQ10 for 3 months superior to placebo; 48% of subjects had ≥ 50% reduction in attack frequency, NNT = 3 (Sandor, 2005 PMID: 15728298). In another study of 1,550 migraine patients from 3-22 years old (mean 13.3 years), low CoQ10 levels were detected in 33%. After roughly 3 months of supplementation with CoQ10 at doses of 1-3 mg/kg, headache frequency and disability were reduced and CoQ10 levels were repleted (Hershey, 2007, PMID: 17355497). CoQ10 was ‘strongly recommended’ for migraine prophylaxis by the CHS (Pringsheim, 2012), ‘possibly effective’ by AAN. (Holland, 2012, doi: 10.1212/WNL.0b013e3182535d0c.).
          1. Use q-gel or a liposomal bound product. (Reduced form, ubiquinol, is better absorbed and more effective in CHF patients with presumed intestinal edema compared to standard ubiquinone, unknown if this is relevant to migraine use (Langsjoen, 2008 PMID: 19096107)).
          2. Dose:
            1. Adults: 300 mg/d, e.g. 100 mg TID. NNT ~ 3
            2. Peds: 1-3 mg/kg
          3. Safety: CoQ10 is generally well tolerated. Testing for deficiency may help tailor which patients will likely benefit from therapy. Safe in pregnancy; may also help prevent pre-eclampsia.
        4. Folate rich foods, esp. if MTHFR C677T variant Effects of dietary folate intake on migraine disability and frequency. Menon S; Lea RA; Ingle S; Sutherland M; Wee S; Haupt LM; Palmer M; Griffiths LR. Headache. 55(2):301-9, 2015 Feb. Randomized Controlled Trial. Research Support, Non-U.S. Gov’t UI: 25598270
  1. Vitamin D. Seasonal and geographic variation in Vitamin D levels may play a role in migraine (Prakash, 2010). Statin use assoc. with lower migraines only if Vit. D > 57 nmol/L (Buettner C1 , PMID: 25424706)
  2. Omega 3 f.a. assoc. with lower migraine freq. The relationship between different fatty acids intake and frequency of migraine attacks. Sadeghi O; Maghsoudi Z; Khorvash F; Ghiasvand R; Askari G.Iranian Journal of Nursing and Midwifery Research. 20(3):334-9, 2015 May-Jun. UI: 26120333. RCT with high Omega 3/6 showed benefit. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. Ramsden CE; Faurot KR; Zamora D; Suchindran CM; Macintosh BA; Gaylord S; Ringel A; Hibbeln JR; Feldstein AE; Mori TA; Barden A; Lynch C; Coble R; Mas E; Palsson O; Barrow DA; Mann JD. Pain. 154(11):2441-51, 2013 Nov.Randomized Controlled Trial. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov’t] UI: 23886520
  1. Probiotics – preliminary studies show decreases migraine, e.g. EcologicBarrier, 2.5×10(9) cfu/g. The effects of the multispecies probiotic mixture EcologicBarrier on migraine: results of an open-label pilot study. de Roos NM; Giezenaar CG; Rovers JM; Witteman BJ; Smits MG; van Hemert S.Beneficial Microbes. 6(5):641-6, 2015 Oct 15.[Journal Article] UI: 25869282
  2. IgG based elimination diet in IBS/Migraine pts. RCT shows significant improvement. IgG-based elimination diet in migraine plus irritable bowel syndrome. Aydinlar EI; Dikmen PY; Tiftikci A; Saruc M; Aksu M; Gunsoy HG; Tozun N. Headache. 53(3):514-25, 2013 Mar. Randomized Controlled Trial. Research Support, Non-U.S. Gov’t] UI: 23216231
    1. Botanicals:
      1. Petasites hybridus (Butterbur) is widely used as a treatment for allergies and migraine prophylaxis. Inhibits lipoxygenase, leukotriene & activation of mast cells, with reduced histamine. May take up to a month to work. (Monograph, 2001). (LOE A, ‘strong recommendation’ by CHS)
        1. Petadolex (PA free) root extract standardized to contain 7.5 mg petasins
          1. Adult dose: 75 mg Gelcap po BID (more effective than 50 mg BID).
          2. Child dose: Ages 10 – 17: one 50 mg Gelcap two times daily. < 10 ‘consult physician’. (don’t give 75 mg cap to children)
          3. No serious adverse events have appeared in any clinical studies to date
      2. Tenacetum parthenium (Feverfew).
        1. Original studies on fresh plant. Migraineurs reported feeling better if ate 2 fresh feverfew leaves every day. Fresh plant can give mouth sores. 10% of long term users can get withdrawal migraines – tapering off should prevent this. Trials on dried plant mixed. May be less effective than other options such as Mg, Riboflavin, and Petasites. Feverfew CO2 extract (MIG-99) B rating AAN, but not recommended by CHS.
      3. Lipigesic-M ( ) (or GelStat Migraine) are SL combos of Tenacetum & ginger, RCTs show benefit if taken early in migraine attack (age 12 – 60). Conclusion: ‘Sublingual feverfew/ginger appears safe and effective as a first-line abortive treatment for a population of migraineurs who frequently experience mild headache prior to the onset of moderate to severe headache’. Well tolerated, can use with other migraine medications. (Cady RK, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™ M) in the treatment of migraine. Headache. 2011 Jul-Aug;51(7):1078-86. doi: 10.1111/j.1526-4610.2011.01910.x. Epub 2011 Jun 1). Ginger alone also has some benefit.
        1. Safety: Avoid in pregnancy
      4. Gingko:
        1. Ginkgo contains flavone glycosides that are potent antioxidants with neuroprotective effects and terpene-lactones, which block platelet activating factor (PAF) that is important for mediating inflammation and the sticking of inflammatory cells to blood vessels. Ginkgolide B modulates the action of glutamate in the CNS.
        2. Combo of Ginkolide B, CoQ10 and Vit. B12 reduced migraine frequency & severity in adults and children. (Usai et al, Neurol Sci, 2010. doi: 10.1007/s10072-010-0321-6). Ginkgolide B/CoQ10/Riboflavin/Magnesium complex in small pediatric study effective for prophylaxis (Esposito, M. doi: 10.1007/s10072-010-0411-5. Epub 2010 Sep 25)
        3. The majority of research has been conducted on doses of 120-240 mg standardized extract standardized to 24-27% flavone glycosides and 6-7% triterpenes per dose, taken at once or in two divided doses. Generally well tolerated.
      5. Nervine botanicals for stress induced migraines:
        1. Milky oat seed (gentle, safe for adults and children –‘meditation in a bottle’,
        2. Kava (root only, aqueous extract, no more than 200 mg/d of kava lactones). Great if head & neck tension),
        3. Sculletaria lactiflora (Skullcap – stronger than milky oat seed – good for the hypersensitive person)
      6. Adaptogens
        1. Ashwagandha (good for stressed/burned out, busy mind)
        2. Rhodiola (stress, chronic fatigue with migraines)


      1. Good combination proprietary products:
        1. Migra-Relief has Butterbur
        2. Ayurvedic migraine tx protocol Response to Ayurvedic therapy in the treatment of migraine without aura.Vaidya PB; Vaidya BS; Vaidya SK.International journal of Ayurveda research. 1(1):30-6, 2010 Jan. UI: 20532095
  • Pharmaceutical Management
    1. Most regimens are highly individualized. Some patients respond to certain “Triptans,” for example, and not to others. Often, several months of trial and error are required to establish adequate symptom control. Most migraineurs begin self-treatment by attempting to decrease sensory stimuli such as seeking dark, silent rooms. Sometimes, just withdrawal from light and noise, and a good sleep can relieve the symptoms of an acute migraine. Pharmacologic treatment of the pain associated with a migraine-in-process can range from over-the-counter acetaminophen to intravenous narcotics. The balance between efficacy, efficiency, and adverse effects can be a tenuous and challenging path at times.
  • Acute migraine tx:
    1. OTCs: metoclopramide (10 mg) and aspirin (1000 mg) offered effective pain relief and reduction of nausea and vomiting with minimal adverse effects (Kirthi, 2013). Can try Acetaminophen for mild migraines
    2. NSAID’s (Toradol is a good acute rescue)
    3. Narcotics/antiemetics (Compazine good choice – these work via increasing dopamine)
    4. Ergotamines, e.g. DHE can be very effective in aborting migraines.
    5. Triptans – efficacy 60% po/nasal, 80% for injectable
      1. Nasal spray works twice as fast. (Don’t sniff)
    6. 30% will have recurrence, because of short 1/2 life.
      1. Imitrex po-use 100 mg tabs stat.
      2. Amerge has nice SE profile & lasts longer.
      3. Do a ‘pre-op’ evaluation. Might do EST if high CAD risk or > 50 y/o & want to use triptan.
    7. Combo of Triptan + NSAID (e.g. Naprosyn, aspirin) superior to either alone.
    8. Adding anti-emetic often helpful & may also reduce headache
    9. Avoid Bulbalbital (high potential of dependence)- or at least limit to very sparing use.




  • Prophylactic tx:
    1. The decision to pursue prophylactic therapy is highly individualized, and necessitates careful discussion with the patient. There are no well-accepted “rules” for initiation of prophylactic therapy. The frequency, duration, and responsiveness to acute therapy is important, but less so than the overall impact upon the patient’s life. 
Often the patient’s medical history can dictate appropriate interventions. For example, in a patient dealing with hypertension, a beta-blocker may be suitable for both conditions, and reduce the risk of drug interactions from multiple agents. 
It is important to allow the prophylactic regimen ample time before proclaiming it ineffective. Often several months are required, depending upon the frequency of migraine flares.
    2. Treat HTN thoroughly. Good evidence that antihypertensives in general can prevent migraine headaches, although the mechanism of action is unclear. A meta-analysis of 94 studies reporting the effectiveness of various drugs (thiazides, beta-blockers, ACEI/ARBs) at controlling hypertension, analyzed the number of patients reporting headache (of any type). One third fewer people reported headache in the treated groups (8.0%) than in the placebo groups (12.4%) (Law, 2005
      1. Anti-HTN drugs:
        1. Beta blockers: e.g. Timilol, blocadren
      2. Anti-depressants:
        1. Amitriptyline works well for prophylaxis
        2. SSRI’s & SNRI’s
      3. Anti-convulsant meds (often limited by SEs):
        1. Topamax (avoid if nephrolithiasis)
        2. Gabapentin blocks sodium channels. It is used primarily in chronic neuropathic pain, blocking extracellular pain signaling. It has been shown to clearly reduce migraine frequency, and also positively impact duration, and quality of life among migraineurs. Mild adverse effect profile, with dizziness and somnolence predominating.
        3. Zonisamide is an anti-epileptic drug with multiple putative mechanisms of action that has been suggested to be effective in migraine prophylaxis in small case series and is used in clinical practice
        4. Depakote – valproate. Can produce weight gain, nausea, tremor, and alopecia
        5. Lacosamide, a newer anti-epileptic drug that may work by decreasing cortical hyper-excitability by blocking sodium channels, has been found to be useful in chronic migraine and medication overuse headache in small non-controlled case series (Krusz, 2010)
      4. NSAID, e.g. Naprosyn during menstrual migraines shown effective in studies.
      5. Placebo effect very strong in migraine. Example: rizatriptan (Maxalt) labeled as placebo was no more effective than placebo labeled as Maxalt


  1. How to handle analgesic rebound:
      1. If tapering off analgesics (don’t stop analgesics abruptly), consider steroids, e.g. Prednisone 100mg or Decadron 4 mg TID & taper over about 10 days, possibly with nasal Imitrex or DHE.
      2. Tramadol can be used to help rebound.
      3. Try to avoid opioids – have vasodilator effect & can lead to rebound and dependency.
      4. Anti-inflammatory meds have less chance of rebound.
      5. Caffeine has strong rebound.
      6. New evidence that overuse of analgesics may actually damage neurological center that turns off pain in CNS.”

Integrative approach to anxiety





  1. Overview
    1. Anxiety disorders in ¼ adolescents & ~ 1/5 adults
    2. Main driver of anxiety is often thoughts and images. Focusing on breath helps people get out of this mind trap.
    3. Often co-morbid with depression, substance abuse
    4. Commonly have impaired judgment & memory, vague somatic sx
    5. Patterns include generalized anxiety, panic, OCD, PTSD, phobias. Many patients do not meet DSM specific criteria for a discrete sub-type.
      1. Panic attacks
        1. May have different sx with different attacks in same pt.
        2. ½ become depressed.
        3. Often associated with chronic medical conditions such as asthma, COPD, arrhythmias, hyperthyroidism
      2. Risk & aggravating factors:
        1. High stress load, insomnia, losses
        2. Lack of exercise
  • Poor diet, esp. high GL, low Mg, B6, B12, Folate, Vit. D
  1. Food scarcity
  2. Meds/substances:
    1. Rx: Sympathomimetics, Beta agonists, Corticosteroids, OCPs
    2. OTC: Energy drinks, SAMe (esp. > 1 G/d), Guarana, Yerba mate
    3. Drug abuse: Cocaine, Meth, ETOH
  3. Diagnosis:
    1. Clinical
      1. BAI
      2. Visceral Sensitivity Index – validated for GI anxiety (Jerndal, P. 2010, 920367800)
  • Ddx:Disease States Associated with Anxiety
    1. Endocrine: Hypo- or hyperthyroidism, Hyperadrenalism, Pheo
    2. Vestibular dysfunction
    3. Cardiac: CHF, arrhythmia
    4. Respiratory: COPD, PE, Pneumonia, Hyperventilation, Oxygen Hunger
    5. Vitamin B12 deficiency
    6. Porphyria
    7. Neoplasms
    8. Encephalitis
    9. Drugs: methamphetamine, cocaine, stimulants
  • Munchausen’s Syndrome
  • Environmental: Lead toxicity, Pesticide exposures


  1. Studies
    1. HRV
    2. EDST (Electro dermal skin testing) may differentiate responders to relaxation and energy therapies
  2. Labs:
    1. R/O anxiety mimics: e.g. TSH, RBC Mg
    2. FLP: Anxiety increases T. cholesterol (depressed pts. tend to have low T. cholesterol)
  • Serum or salivary cortisol increases (burnout or chronic fatigue associated with low awakening cortisol)
  1. Treatment overview: Allow several months for patient to implement suggestions, one simple small change a week.
    1. Avoid stimulants such as:
      1. Mental/Emotional: Horror/action movies, Media news of crimes
      2. Avoid/resolve angry or conflicted relationships
  • Medications: Decongestants such as phenylephrine, appetite suppressants, methylphenidate and other drugs to treat ADHD, migraine meds that contain caffeine such as Excedrin, albuterol, corticosteroids (check with your doctor first of course)
  1. Eliminate all caffeine: coffee, strong tea, sodas, energy drinks.
  2. Stimulating herbs: yerba mate, guarana, high dose SAMe
  1. Healthy lifestyle:
    1. Re-connect with the body to help ground the mind and avoid un-anchored imagination that drives much anxiety. The body is designed to move and needs to do so for health and wholeness. It is our friend and unlike our ordinary mind it never lies, guiding us on how we reallyfeel. Virtually all physical tensions are a sign of lack of emotional clarity – of blockage of the flow of our body’s energy. Listen to and learn to trust the body’s deep wisdom.
      1. Regular physical activity – aerobics, strength, mind-body
      2. Meditation
    2. Whole foods: Key aspects:
      1. Low glycemic load, especially commercial baked (i.e. flour) products including whole wheat
      2. Adequate healthy fat:
        1. Balance Omega 3/6 fatty acids:
        2. Use extra-virgin olive oil as a main cooking oil.
        3. Fat in avocado, omega-3 eggs support brain functions.
      3. Vegetables 5 – 7 servings daily
      4. Magnesium– def. can trigger anxiety and depressive sx. Sources: nuts, green vegetables
      5. Vitamin D
  • Healthy sleep.
    1. Insomnia (in 80% of psych dx, 25% of children) is prodromal, exacerbating and comorbid with most anxiety & depression – all ‘feed on each other’.
    2. Decrease REM latency leads to REM replacing deep restful sleep early in night.
    3. Loss of REM leads to lack of nocturnal suppression of CNS neurotransmitters and lack of normal down regulation of amygdala based emotional reactivity. Anxiety suppresses REM, leading to more emotional reactivity and a vicious cycle. – See Sleep handout
  1. Exercise:
    1. Contralateral movements such as walking establish healthy rhythms in the brain
  2. Gut microbiome normalization:
    1. Bifidobacterium longum NCC3001 normalized anxiety-like behavior and levels of brain-derived neurotropic factor in mice with infectious colitis(Bercik, 2011).
  3. Psychotherapeutic approaches with clinical research support:
    1. CBT, DBT – (involves moderating their emotions, rather than talking a lot), Exposure therapy have less relapse rate than treatment with just medications.
      1. Panic with abnormal HRV responds to CBT but not very well to pharmaceuticals
    2. Online & telephone mental health programs – preliminary studies show benefit
  • Situation-specific anxiety tx, e.g. phobias, PTSD:
    1. Virtual Reality Graded Exposure Therapy (VRGET) – preliminary evidence of benefit for phobias, GAD, Panic, PTSD
    2. Systematic desensitization,
    3. Clinical hypnosis and other similar techniques.
    4. Kundalini yoga left-nostril breathing technique reduces OCD sx in a small controlled trial.
  1. Relaxation (all require regular practice)
    1. Mindfulness alone or as part of MBSR
    2. Autogenic training, Guided imagery, Clinical hypnosis
    3. Progressive Muscular Relaxation (PMR): isolate 1 muscle group, tense for 10 sec, then let go all at once. Muscles if not moved will continue to relax further.
      1. PMR can help OSA, CPAP adherence, anxiety, sleep, caregiver stress, pain.
    4. Breathing techniques:
      1. ‘Breathing is the bridge between mind and body, the connection between consciousness and unconsciousness, the movement of spirit in matter’ ‘The single most effective relaxation technique I know is conscious regulation of the breath’ – A. Weil.
      2. Bridge between the voluntary and involuntary nervous systems.
  • Exhalation is ‘first’ in some cultures.
  1. Most people do not know how to breathe.
  2. Slow deep breathing can improve HR, BP, emotional state
  3. Need to be more alert: Bellow breathe:
    1. 10 – 30 seconds
    2. Stimulating, alerting
    3. Indications: need to be more alert, e.g. driving, on call
  • Need to calm down: 4-7-8 Breath. MUST DO TWICE A DAY, including prior to sleep.
    1. Powerfully balances autonomic tone. The ‘7’ pause is when get strong PNS stimulation. At least a month to see clinical effects. Make take several months to improve excess SNS in some cases.
    2. Breathe in thru nose, out thru mouth with whoosh thru pursed lips.
    3. Start 4 cycles (after a month can increase to 8 cycles), at least twice a day. Can do as many times per day as needed for facilitating calmness, but no more than 8 cycles at a time. Lowers BP, HR. Helps sleep, digestion. May help PTSD, A fib, etc.
  • Other calming breathwork minis:
    1. Ten to one: Count down from 10 to 1 on slow outbreaths
    2. 1,2,3, 4: As breathe in count slowly from 1 to 4, as breathe out also count slowly from 1 to 4.
    3. Breathe counting: count 1,2,3 between in & outbreaths
    4. In & out: Inbreathe ‘I am’, outbreath ‘at peace’
    5. Square breathing: Inbreathe visualize vertical & horiz, outbreath vertical & horiz. to form square.
    6. Alternate nostril breathing in 90 minute cycle. Stimulates contralateral brain hemisphere.
  1. Craniosacral therapy works with restoring the ‘CNS respiratory cycle’ called ‘primary respiration’, which can be disturbed by birth trauma, lack of a large first breath of life, extreme emotional trauma or any trauma in early life if no crying or screaming. Need evidence base.
  2. Biofeedback such as Heart Rate Variability (HRV).
  1. Psychopharmaceuticals
    1. DOC: SSRIs, e.g. paroxetine; SNRIs, e.g. venlafaxine.
      1. Start low, build up
      2. Adverse effects: transient nausea, headache; drowsiness, decreased sex function
  • Folate 1 –5 mg/d can augment SSRI, SNRIs (caution with excess folate)
  1. Benzodiazepines (not to be used beyond 2–4 wks.). Occasional prn use ok. Dependency issues. ~1/2 get withdrawal after only 1 month of use.
  2. Antihistamines: hydroxyzine
  3. TCAs: Imipramine tx GAD and panic, clomipramine tx OCD.
    1. TCAs have more side effects than either SSRIs or venlafaxine, so are generally used when patients do not tolerate or respond to SSRI/SNRI therapy. TCAs should be avoided in patients considered at risk of suicide, due to their potential cardiac and CNS toxicity after overdose.
  4. Buspirone 5-HT1A receptor,
    1. Indications: GAD. Up to two weeks to begin working.
    2. SEs:generally well tolerated, adverse effects include headache, nausea, dizziness and nervousness, insomnia
  5. Beta-blockers
    1. Indications:not FDA approved but used for physical symptoms of anxiety and panic, such as trembling and sweating, e.g. when person with social phobia must face a stressful situation, such as giving a speech.
    2. Dose:propranalol
      1. Adverse effects:caution in diabetics as it can mask symptoms of hypoglycemia. The most common side effects are dizziness and fatigue.
  • Contraindicated: asthma, severe heart failure
  1. Pregabalin (Lyrica) (not FDA approved for anxiety)
  2. Hydroxyzine (takes up to 6 weeks to have an effect?)


  1. Supplements/ Botanicals: Best evidence is for Kava kava & Inositol, others have modest evidence
  2. Kava Kava( Piper methysticum)
    1. Indications:Good evidence for GAD, anxiety symptoms associated with menopause, likely effective and safe approach for discontinuing benzodiazepines following chronic use
    2. Dose:standardized kava preparations (use dried root powder or aqueous extracts only) 100–200mg/day. For benzodiazepine withdrawal, titrate up to 300mg/day while tapering off benzo’s
    3. Adverse effects: Kava is generally well tolerated. Uncommon adverse effects include GI distress, rash, headaches and dizziness. More serious questions of its safety were raised after case reports suggested that it might cause liver damage.
      1. Traditionally, kava was made into tea by adding water to the roots. Almost all cases of liver damage that have been reported were from kava products that had been extracted with alcohol and/or acetone or used areal parts. Patients should purchase kava from a reputable manufacturer and only use dried powdered root (not an extraction), or until the evidence is clearer, look for products sold as “aqueous” extracts, meaning that water was used as a solvent instead of acetone or alcohol.
    4. Interactions:kava interacts with numerous drug metabolizing enzymes


  • Inositol: part of the vitamin B-complex is required for proper formation of cell membranes and is important for nerve transmission.
    1. Indications: Good evidence that Inositol in doses up to 20g/day reduces the severity and frequency of panic attacks. RCT: inositol 12 g/day and imipramine equally effective in reducing the frequency and severity of panic attacks and agoraphobia (Benjamin, 1995). RCT: inositol (up to 18g/day) and fluvoxamine (up to 150mg/day) had similar efficacy in reducing the frequency of panic attacks (Palatnik, 2001).
    2. Dose:start with 2–4 grams BID, increasing to 4–6 grams TID as needed e.g. in juice. Titrate up gradually to avoid GI distress. The powder provides 2.4 grams per teaspoon or 7.2 grams per tablespoon.
    3. Adverse effects:Well tolerated. GI distress


  • 5-HTP & L-tryptophan
    1. Background:L-tryptophan and 5-hydroxytryptophan (5-HTP) are essential precursors for serotonin synthesis and there are small studies evaluating their role in anxiety. 5-HTP is extracted from the G. simplicifolia, a plant native to West Africa. In a double-blind study, 58% of generally anxious patients (N=79) randomized to L-tryptophan 3g/day reported significantly greater reductions in baseline anxiety compared to placebo. Preliminary findings suggest that 5-HTP may inhibit panic attacks.
    2. Indications:Anxiety, panic, insomnia. Likely safe to use with SSRIs but monitor for Serotonin syndrome (rare)
    3. Dose:5-HTP at 50mg to 100mg, three-times-daily is generally well tolerated without excessive daytime sedation. Gradually increasing 5-HTP in increments of 50mg to 200 to 400mg at bedtime often reduces daytime anxiety and improves the quality of sleep in chronically anxious patients. 5-HTP at 50mg to 100mg TID is generally well tolerated without excessive daytime sedation.
    4. Adverse effects:In 1989 and 1990, ingestion of contaminated l-tryptophan caused an epidemic of eosinophilia myalgia syndrome (EMS) that affected over 1500 people and caused at least 38 deaths (FDA 1998). There have only been a very small number of cases (10) of EMS possibly linked to the use of 5-HTP in more than 20 years of use and most experts believe the risk is rare to non-existent.
    5. At dosages of less than 50 mg/kg/day, there appear to be no toxicities associated with 5-HTP administration (Semont, et al. 2000). Serotonin syndrome has not been observed in patients administered 5-HTP in combination with SSRIs or MAOIs. Thus, it appears that 5-HTP may be safely combined with conventional anti-anxiety drugs, though, it is still prudent to monitor for treatment-emergent symptoms of serotonin syndrome including insomnia, agitation and nervousness (Turner, 2006).
    6. Side effects include nausea, vomiting and insomnia and are related to dose and can minimized when 5-HTP is started at doses of 25mg/day and gradually increased over several weeks to a daily regimen that is well tolerated and produces consistent anti-anxiety effects.


  • Bacopa (Bacopa monnieri)
    1. Background:Bacopa leaf is used in Ayurvedic medicine to help with memory, cognition, as a treatment for epilepsy and enhance learning.
    2. Indications:Anxiety, cognition? Bacopa in combination with gotu kola (Centella asiatica) has been shown in DBRCT to effectively reduce general anxiety symptoms.
    3. Dose:200–400 mg per day in 2-3 divided doses of standardized extract (20% bacosides A + B).
    4. Adverse effects: Safety studies are very reassuring.
    5. Interactions?


  • Gotu Kola (Centella asiatica)
    1. Background:Gotu kola leaf has been valued as a medicinal herb in India, China and Indonesia for millennia. It was traditionally used to heal wounds, enhance cognition, improve circulation and treat leprosy. Clinical studies support some of these uses including the treatment of wounds and burns, improve chronic venous insufficiency, and improve insomnia. A animal study demonstrated anxiolytic activity.
    2. Indications:Gotu kola in combination with Bacopa monnieri has been shown in DBRCTs to effectively reduce general anxiety symptoms.
    3. Doseis generally 1 gram 2–3 times per day of leaf or 300 mg standardized extract (10% asiaticosides) taken twice daily
    4. Adverse effects
    5. Interactions:


  • Lemon Balm (Melissa officinalis)
    1. Background:Member of mint family used to relieve stress and anxiety for millennia. ESCOP (European Scientific Cooperative On Phytotherapy) endorses lemon balm for tenseness, restlessness, irritability, and symptomatic treatment of digestive disorders, such as minor spasms, and externally for herpes labialis (ESCOP, 1997). The German Commission E approves the internal use of lemon balm for nervous sleeping disorders and functional gastrointestinal complaints.
    2. Few studies evaluating the use of lemon balm for anxiety as a monotherapy. Studies of the combination of lemon balm and valerian (Valeriana officinalis) suggest it is beneficial for anxiety and insomnia.
    3. Indications:Adjunct for anxiety
    4. Dose:~ 1 G of lemon balm herb BID
    5. Adverse effects:Lemon balm is quite safe and may be taken as tea or in capsule.
    6. Interactions:


  • L-Theanine
    1. Background: L-theanine is an amino acid extracted from green tea (Camellia sinensis). Widely used to treat anxiety symptoms and depressed mood in Japan and other Asian countries. Studies demonstrate a calming effect within 30 to 40 minutes after ingestion when taken at doses of 50 to 200 mg. The calming effect lasts approximately 8–10 hours. Theanine is also found in some mushrooms. Theanine has historically been used for its relaxing and anti-anxiety effects. It’s thought that theanine might work for anxiety by increasing levels of GABA and serotonin.
    2. Indications:Anxiety
    3. Dose:Use Sun L-theanine. Moderate anxiety symptoms often improve with a regimen of 200mg once or twice daily. More severe anxiety symptoms may require doses up to 600mg to 800mg daily, taken in increments of 100mg to 200mg evenly spaced throughout the day.
    4. Adverse effects:L-theanine does not cause drowsiness, slowed reflexes or impaired concentration, there is no risk of developing tolerance or dependence, and there have been no reports of serious adverse side effects
    5. Interactions:no known interactions with other natural products, benzodiazepines or other pharmacological agents. Might mildly lower BP, so might be additive with anti-hypertensives.


  • Passion flower(Passiflora incarnata)
    1. Background:The dried aerial parts of passion flower (Passiflora incarnata) were traditionally used as a sedative and it is approved by the German Commission E, as well as in France and other European countries, for the treatment of insomnia and nervousness. Passion flower extract is commonly used to treat anxiety; however, few double-blind, placebo-controlled studies have been done. In one small study, passion flower extract 45 drops/day and oxazepam (a benzodiazepine) were equally effective in reducing generalized anxiety (Akhondzadeh, 2001). Patients taking oxazepam reported significant impairments in job performance at doses that lowered anxiety however patients in the passion flower group did not experience similar impairments.
    2. Indications:adjunct to tx anxiety, often mixed with other herbs
    3. Dose:500–2000 mg per day
    4. Adverse effects:
    5. Interactions:


  • Rhodiola (Rhodiola rosea)
    1. Background:Rhodiola (Rhodiola rosea) or Arctic root or golden root, used in traditional medicine in Russia and the Scandinavian countries for centuries. There are many possible actives in rhodiola but the most striking appear to be rosavins, rosiridin and salidroside.
    2. Indications:Anxiety, fatigue. Small studies show improved anxiety with 340 mg rhodiola extract per day for 10 weeks.
    3. Dose:SHR-5 is a proprietary extract standardized to 3% rosavin and 0.8% salidroside (Swedish Herbal Institute, Vastra Frolunda, Sweden). The dose used in clinical trials ranges from 200–680 mg/d. It is wise to start with the lower dose (100–150 mg/d) for 1–2 weeks and then increase up to a dose of 340–400 mg/d.
    4. Adverse effects:Generally well tolerated. Can cause agitation and irritability, dizziness, dry mouth
    5. Interactions:


  • Valerian  (Valeriana officinalis)
    1. Background:Traditional use & lower quality studies support mild sedative and anxiolytic. Commission E approved as an anxiolytic and a sleep aid. May combine with St. John’s wort (Hypericum perforatum) for the treatment of depression and depression with co-morbid anxiety, combined with lemon balm (Melissa officinalis) for relaxation & insomnia in adults & children.
    2. Indications:Anxiety, chronic insomnia
    3. Dose:The dose range for anxiety is typically 2-6 grams per day of valerian root in capsule or extract.
    4. Adverse effects:smells like dirty socks
    5. Contraindications:The German Commission E lists no contraindications, ESCOP contraindicates its use in children under 3 years, the World Health Organization (WHO) contraindicates is use in pregnancy.
    6. Interactions:
  • N-Acetylcysteine (NAC)
    1. Background: When used as add-on therapy, acetylcysteine has produced favorable results in patients with autism, OCD, bipolar disorder, or schizophrenia;
      1. See: NAC for Neuropsych disorders – Am J Health-Syst Pharm—Vol 72 Jun 1, 201
      2. Oral acetylcysteine for neuropsychiatric disorders – Am J Health-Syst Pharm—Vol 72 Jun 1, 2015 p 923 – 928
    2. Indications: OCD and it’s variants, other Neuropsych disorders
    3. Dose: Average effective dose is about 1200 mg – 2 G/day. Can start at 600 mg/day.
    4. Adverse effects: generally safe and well tolerated
    5. Contraindications:
    6. Interactions:
  1. Calm Aid or Silexan (Natures Way) for anxiety has been clinically studied and is comparable to lorazepam. Int J Neuropsychopharmacol.2014 Jun;17(6):859-69. doi: 10.1017/S1461145714000017. Epub 2014 Jan 23. Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep – A randomized, placebo-controlled trial Siegfried Kasper Ion Anghelescu, Angelika DienelDOI: (some funding bias possible).



  1. Combination botanicals:
    1. Phytocalm
  2. Aromatherapy
    1. Essential oils can have potent effects on balancing autonomic nervous system, esp. Lavender or Bergamot in limited studies.
    2. Aromatherapy, a complete guide to the healing art, by Keville and Green; Crown publishing group, Random house



  1. Energy Medicine
    1. Regular Reiki treatments –preliminary evidence helps anxiety
    2. Healing Touch (HT) and Therapeutic Touch (TT) –preliminary evidence helps anxiety, effect may last 2 weeks
      1. TT studies show benefit for chronically anxious patients and in anxious non-demented elderly nursing home patients but there is limited evidence for anxiety reducing effects of TT in healthy adults. High patient satisfaction
    3. Emotional Freedom Technique – basic tutorial at:
      1. Emotional Freedom Technique (EFT) is “an emotional, needle free form of acupuncture.” invented by Gary Craig from his work with Roger Callahan and Thought field theory, a branch of psychology aimed at overcoming phobias. EFT is an energy psychology technique that uses fingertip tapping of facial and chest points to move energy and help shift psychological difficulties. It is advertised to be an effective treatment for eating disorders, fears, phobias, depression, PTSD, and addiction. Practitioners of EFT state that EFT often works when nothing else does, and that it works for almost everything. Research is lacking for EFT; there are a few small studies published with promising results for phobias fibromyalgia, PTSD, and anxiety.
      2. Certification in EFT is obtained by studying course material by video and completing 100 treatment sessions. The material may be downloaded off the EFT website, Patients can work with a practitioner, or learn the points and treat themselves on a regular basis.
  • Basic premise of EFT: “The cause of all negative emotions is a disruption in the body’s energy system.” Once one finds those energy disruptions, use the tapping process to correct them. The EFT Tapping Basic Recipe blends focused wording with a 9 point Tapping sequence.
  1. Basic steps EFT:
    1. Choose a target for EFT – an emotion, block, belief or abundance issue.
    2. Scale the intensity of the belief or issue (1 – 10)
    3. Tap Karate chop point while repeating the set up statement, e.g. ‘Even though I have these money blocks, I deeply and completely accept myself’
    4. Negative tapping sequence Say your reminder phrase at each tapping point, e.g.“these money blocks” (8 points, 7 – 10X each): Top of head, eyebrow (at the beginning of the eyebrow, just above and to one side of the nose),side of eye (on the bone bordering the outside corner of the eye), under eye (on the bone under an eye about 1 inch below your pupil),under nose (on the small area between the bottom of your nose and the top of your upper lip),chin (midway between the point of your chin and the bottom of your lower lip), collarbone (the junction where the sternum collarbone and the first rib meet), under arm (on the side of the body, at a point even with the nipple (for men) or in the middle of the bra strap (for women). It is about 4 inches below the armpit)
    5. Positive tapping sequence: (same points, positive statement(s) – same or different each point), e.g. “I cultivate abundance’, ‘I choose peace’, ‘I embrace change’
    6. Finish with two deep breaths.Can rescale issue to assess for change
  2. Evidence for EFT: Small RCTs show benefit for anxiety (UI: 27125158, UI: 26539218), in war-injured vets (UI: 25530137), tension headaches (UI: 23452711). Promising results from WHEE (wholistic hybrid derived from eye movement desensitization and reprocessing and Emotional Freedom Techniques (WHEE), Emotional Freedom Techniques (EFTs), and cognitive behavioral therapy (CBT) (UI: 19913760, UI: 16290899).
  1. Traditional Chinese medicine (TCM)
    1. Balance of Yang (energy, alerting) predominant during day, and Yin, predominant during night. Shen – spirit or mind shines out thru the eyes. At night, with adequate Yin, Shen returns to rest in the heart.
    2. Depression – three forms:
      1. Lack of Yang vitality. Example: SAD – tx w light therapy
      2. Chi stagnation (liver depression) The liver is in charge of the smooth flow of all the energy (chi) in the body. Depression, irritability. Acupuncture & exercise ideal for this form of depression. Modern sedentary society leads to chi stagnation.
  • ‘Dampness clouding the heart’ – Shen or spirit gets stuck in the heart. Lifestyle change and herbals main therapeutics. Acupuncture not as helpful.
  1. Anxiety – lack of Yin calmness leads to scattered, agitated mind. Yin is the foundational ‘ballast’ for the mind.
    1. Menopause with drop of estrogen (which is yin) leads to anxiety and insomnia
  2. Bipolar – complex. Swings from yang and yin deficiency
    1. Liver depression/ chi stagnation often severe – becomes ‘hot’, transforming into ‘fire’ – mania.
    2. Severe dampness congeals into phlegm which can overheat and become ‘phlegm fire’ with disordered thinking.
  3. PTSD/major stress – auricular 5 needle nada protocol
  4. Drug addiction/ psychosis – auricular acupuncture plus biway at top of head
  5. Oil/fat is Yin and calms the brain.
  6. Chinese herbal formulas for many mental illnesses. Includes ‘dragon bones’ – fossilized dinosaur bones, ground pearls, resins such as amber are in formulas to calm the spirit – ‘shen calming’.
  7. Acupuncture & Qigong – Preliminary evidence of benefit for anxiety
  8. Resources Licensed acupuncturists:National Certification Commission for Acupuncture and Oriental Medicineor the American Academy of Medical Acupuncture
  9. Tai chi – good evidence of benefit for anxiety
  10. Massage– some evidence benefit for anxiety. Can be used even in ICU preemies, with benefit such as weight gain.
  13. Music – particular types of music likely ease anxiety. RCT conventional cognitive therapy versus music-assisted reframing showed latter had greater reductions in overall anxiety (Kerr, 2001).
  14. Binaural sound: When headphones are used to route slightly different frequencies of sound to the right and left hemispheres, the brainstem constructs binaural beats on the basis of the frequency difference between sounds. Particular binaural beats consistently induce a calm, relaxed state, while others facilitate increased attention or arousal (Atwater, 1999).

Sample Protocol‐Anxiety

  • Inositol‐ 4 to 6 grams bid or tid
  • 5HTP 50 to 200 mg tid
  • Relaxation, meditation, walking, yoga, journaling
  • Psychotherapy, EMDR if trauma
  • L‐theanine 200 to 400mg bid
  • No caffeine
  • If obsessive: NAC 600‐1200mg bid