Anxiety Panic Disorder Naturopathic Protocol

Health Condition Naturopathic Protocol

This Anxiety Panic Disorder Naturopathic Protocol is provided as information for patients of HealthMasters Naturopath Kevin Tresize ND as part of a treatment plan to assist patients with understanding of their treatment plan. It is important to note that this is a summary only and is intended to assist discussion between practitioner and patient as part of consultations. This Anxiety Panic Disorder  Naturopathic Protocol may be changed to suit the individual requirements of the patient and should not be substituted for medical advice, diagnosis or treatment.

 HealthMasters Naturopath Kevin Tresize ND

 

Pathophysiology: Anxiety Panic Disorder Naturopathic Protocol

  • Anxiety disorders are associated with an imbalance of activity in the hippocampus and the amygdala (emotional centres of the brain).[1]
  • The amygdala activates the hypothalamic-pituitary-adrenal (HPA) axis and is responsible for the expression of fear, aggression and defensive behaviour. Together, the amygdala and hippocampus (memory, learning and emotional context of events) are involved in retrieval of both emotional and fear-related memories.
  • Chronic HPA axis activation stimulates microglia to move into a proinflammatory immune state, known as M1 phenotype. Once in this state, microglia generate proinflammatory cytokines, increase oxidative stress[2] and amplify glutamate levels.[3],[4] Long-term microgliosis leads to changes in brain architecture (enlargement of the amygdala and shrinkage of the hippocampus), a disturbance of the serotonergic system (reducing serotonin levels),[5],[6] and the pathological presentations seen in anxiety.
  • Noradrenalin plays a central role in amygdala memory consolidation, while adrenalin and cortisol have been shown to compromise hippocampus function and volume.[7]
  • Decreased gamma-aminobutyric acid (GABA) signalling and increased excitatory neurotransmission by glutamate also underlie anxiety disorders.[8] Specifically, a hyperglutamatergic state in the basolateral amygdala drives fear and sleep disturbances, common to anxiety disorders.[9],[10]
  • Generalised anxiety disorder (GAD) is diagnosed in people with excessive worry and anxiety, which the person finds difficult to control. Anxiety occurs more days than not and has been present for at least six months.[11]
  • Panic disorder is characterised by an abrupt surge of fear that reaches peak within minutes, in which four or more of the following symptoms develop, palpitations, sweating, trembling/shaking, feeling of choking, chest pain, nausea, feeling dizzy/lightheaded, feelings of unreality, fear of losing control, fear of dying, paraesthesia, and heat sensations.[12]

 

Consultation Overview: Anxiety Panic Disorder Naturopathic Protocol

Identify Risk Factors

In Clinic Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for further guidelines:

  • Have patient complete the Mood and Stress Questionnaire and the Depression Anxiety Stress Scales (DASS).
  • Examine family history of anxiety or other psychiatric disorders.
  • Investigate the presence of comorbid depression or other psychiatric disorders.
  • Examine sleep patterns.
  • Investigate substance abuse/dependency including illicit drugs, nicotine, alcohol and caffeine.
  • Screen for symptoms of dysglycaemia as a driver of anxiety.
  • Screen for additional comorbidities including cardiovascular disease and gut dysfunction.

Pathology Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for further guidelines:

  • Consider the cortisol awakening response (CAR) test or adrenocoretex stress profile to examine HPA axis function.
  • If presenting with cardiovascular symptoms, refer patient for medical tests including homocysteine, erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hs-CRP).
  • If presenting with blood glucose regulation, refer patient for fasting and/or random blood glucose testing.

 

Identify Signs of Anxiety

  • How many days per week does the patient experience anxiety?
  • How many episodes occur throughout the day and what is their duration?
  • Have patient evaluate intensity using a severity scale of 1 to 10.
  • Assess anxiety presentation e.g. chest palpitations, shortness of breath, tachycardia etc.
  • Assess the presence or history of panic attacks

Physiological alterations in sleep, appetite, cognition and psychomotor activity are commonly seen in anxiety and depression, and various clinical symptoms may present, as outlined in Table 1.[13]

Table 1: Clinical picture of anxiety and depression.[14],[15],[16]

Physical Psychological  Behavioural

Changes in weight

Changes in appetite/cravings

Sleep disturbances

Fatigue

Shortness of breath/rapid breathing

Chest/body pain

Low sex drive

Gastrointestinal symptoms

Crying spells

Constant worrying

Mood swings

Irritability

Lack of concentration

Indecisiveness

Feeling overwhelmed

 

Anhedonia

Withdrawal from family and friends

Relying on substances e.g. alcohol, drugs – stimulants/sedatives

Psychomotor agitation e.g. constant pacing, tapping

Withdrawal from family and friends

 

 

 

 

 

 Key Drivers: Anxiety Panic Disorder Naturopathic Protocol

  • Childhood trauma: Childhood trauma and maltreatment is associated with the onset and symptom severity of anxiety. Childhood trauma disturbs the ability to regulate emotions in a healthy manner, resulting in fewer adaptive emotion regulation skills. Emotion regulation deficits in anxious individuals can lead to maladaptive coping with fear-related stimuli, increasing the possibility of chronic avoidance.[17]
  • Acute or chronic stressors: Chronic or severe stressed-induced activation influences the function and structure of the amygdala neurons, creating maladaptive neuroplasticity and structural changes.[18]
  • Substance abuse: Acute use of many drugs, including cocaine, opiates, nicotine, alcohol, and caffeine activate the HPA axis. Increased corticotropin-releasing hormone (CRH) neuronal signalling increases amygdala activity, which mediates anxiety-like behaviour.[19]
  • Sleep disturbances/insomnia: Insufficient sleep is associated with emotional and mental health problems, including anxiety. Many cases of chronic insomnia have an emotional or psychological basis, with anxiety prevalent among individuals who experience insomnia Additionally, It is common for insomniacs to become anxious about not sleeping, thereby compounding the problem.[20]
  • Inadequate glucose supply: Amygdala function is dependent on an adequate glucose supply. Recurrent hypoglycaemia causes increased noradrenaline transmission in the amygdala and creates anxiety symptoms.[21] Heightened anxiety can occur after high glycaemic index meals (reactive hypoglycaemia) or during times of glycogen depletion such as fasting or prolonged activity.[22]
  • Hyperthyroidism: Anxiety and mood changes are clinical manifestations of persistent elevated levels of free thyroxine (T4) and free triiodothyronine (T3).[23]
  • Gut dysfunction including irritable bowel syndrome (IBS): Gut dysfunction is strongly associated with anxiety. Dysbiosis is prevalent among IBS patients, which can alter mood and emotion via activation of the vagus nerve via gut lumen inflammation (created by dysbiosis).[24]
  • Genetic Predisposition: GAD is a heritable condition with a moderate genetic risk (heritability of approximately 30%).[25]

 

Treatment Priorities: Anxiety Panic Disorder Naturopathic Protocol

  • Remove and/or manage anxiety triggers, including acute/chronic stressors, stimulants (caffeine, alcohol), dysglycaemia, thyroid dysfunction, and/or poor sleep patterns.
  • Regulate HPA-axis activity, reducing excessive production of corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), cortisol, and catecholamines, which induce excitatory glutamate release in the hippocampus.
  • Enhance GABAergic activity to reduce glutamate excitation necessary for strengthening dendritic branching in neuroplasticity, improving the structure and function of the amygdala and hippocampus.
  • Monitor anxiety progression using the symptom diary available in the Your Guide to Stress Less patient booklet, in addition to the DASS and MSQ questionnaires.
  • Monitor changes in pathology
  • Monitor patient’s adherence to dietary, lifestyle and supplementary recommendations using Your Guide to Stress Less patient booklet.

 

Red Flags: Anxiety Panic Disorder Naturopathic Protocol

  • Comorbidity with depression or other psychiatric disorders: Anxiety disorders have a high rate of comorbidity with other psychiatric disorders, including major depressive disorder, bipolar disorder and substance abuse disorders. Additionally, patients with GAD are at risk for poorer quality of life and suicidality.[26] Use the Mood and Stress Questionnaire and DASS questionnaire to assess the patients mental wellbeing and refer to General Practitioner/Psychologist/Psychiatrist where indicated. If patient is deemed at risk of self-harm or harm to others, seek immediate guidance from a Crisis Assessment and Treatment Team (CATT) or call Triple Zero (000) Emergency.
  • Cardiovascular conditions: Anxiety disorders are associated with poor cardiovascular health, including the development and progression of coronary artery disease and heart failure.[27] Screen patient for cardiovascular signs and symptoms using the Cardiovascular Risk Assessment, monitor blood pressure and refer patient for pathology testing, including homocysteine, ESR and hs-CRP. Refer patient to a General Practitioner for assessment if CVD is suspected.

 

Treatment Recommendations: Anxiety Panic Disorder Naturopathic Protocol

Core Recommendations

 

Herbal Support for Hyper HPA and Stress

Dosage: Take 1-2 tablets three times daily

Anxiolytic herbs that enhance GABA activity and work against glutamate-mediated excitability in the brain to alleviate anxiety, nervous tension and agitation.

Mechanism of Action/Clinical Research:

  • Zizyphus has been shown to modify the GABAα receptor subunits expressional levels,[28] which opposes glutamate-mediated excitability in the brain, contributing to its anxiolytic effects.[29]
  • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[30]

A clinical trial involving 154 participants with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety, poor concentration, nausea, tremors, and palpitations.[31]

  • Kudzu has demonstrated β-adrenoceptor blocking activity[32],[33] similar to pharmacological beta-blockers, which are used to reduce the physical effects of anxiety and stress such as palpitations, high blood pressure, tremor and sweating.
  • Magnolia exhibits muscle relaxing effects via GABAergic mechanisms,[34] as well as neuroprotective properties.[35],[36]

 

OR for insomnia or panic attacks, consider:

California Poppy and Passionflower for Sleep

Dosage: For mild anxiety, take 1 tablet twice daily with food.  For insomnia, take 2 tablets once daily with your evening meal.

A blend of sedative herbs that modulate neurotransmitter pathways, including GABA and glutamate, monoamine and catecholamine activity (which support sleep quality), HPA function, formation of synaptic pathways, and brain plasticity.

Mechanism of Action/Clinical Research:

  • Zizyphus activates glutamic acid decarboxylase, which catalyses GABA synthesis, while also sensitising GABA receptors by increasing their subunit expression.[37]
  • Lavender oil promotes a GABAergic response by blocking calcium ion channel activity within neurons and suppressing glutamate excitation, with inhibitory effects comparable to those seen in pregabalin (a pharmaceutical agent that mimics the effects of GABA).[38]

A double-blind, randomised, multi-centre trial involving 170 patients that were prescribed 80 mg/d of lavender oil for 12 weeks showed significant improvements in in anxiety and sleep quality.[39]

  • California poppy stimulates binding of the GABAα receptor site, providing sedative effects.[40]

 

Meta Mag Magnesium, Taurine & Glutamine for Stress

Dosage: Add 2 level scoops (11.9 g) to 200 mL of water, twice daily.

Nutrients that decrease excessive neuronal activity in the amygdala and reduce catecholamine levels, to support a healthy stress response and reduce the effects of physical and psychological stress on the body.

Mechanism of Action/Clinical Research:

  • Magnesium improves resistance to neuropsychological stressors, such as glutamate excitotoxicity, through its actions as a voltage-gated antagonist at the glutamate, N-methyl-D-aspartate (NMDA) receptor site.[41] The reduction of glutamate activity has been shown to increase the actions of the GABAergic systems.[42]
  • Taurine acts as an inhibitory neurotransmitter or neuromodulator, interacting with NMDA receptors to suppress glutamatergic transmission and protect against glutamate excitotoxicity.[43]
  • Zinc acts as an inhibitory neuromodulator of glutamate release, regulating NMDA receptors.[44]

A study of 100 adolescent female students with mood disorders found decreased serum zinc to be inversely correlated with symptoms of anxiety and depression.[45]

  • L-Glutamine is involved in neurotransmitter synthesis and is the precursor for glutamate and GABA.[46]
  • Vitamin C (ascorbic acid) is required for the synthesis of neurotransmitters, including noradrenaline and serotonin.[47]
  • Vitamin B6 is fundamental to the production of many neurotransmitters[48] and is specifically involved in the creation of histidine to histamine, tryptophan to serotonin, glutamate to GABA, and dihydroxyphenylalanine to dopamine,[49] as well as the synthesis of adrenaline and noradrenaline.[50]

 

Vitamins B5, B6 & C for Stress and Adrenal Health

Dosage: Take 1 tablet twice daily with food

Nutritional that support neurotransmission and steroid hormone synthesis, to regulate HPA-axis activity (adrenalin, noradrenalin and cortisol synthesis) and sympathetic and parasympathetic arms of the stress response.

Mechanism of Action/Clinical Research:

  • Vitamin B5 forms part of coenzyme A (CoA), which is essential for the production of acetylcholine[51] CoA is also required for the synthesis of steroid hormones including cortisone.[52]

A meta-analysis investigating the effects of multivitamin supplementation on mood and mild psychiatric symptoms demonstrated significant improvements in perceived stress levels, mild psychiatric symptoms and anxiety, with the most pronounced effects attributed to high-dose B vitamin use.[53]

  • Vitamin B6, is a vital cofactor for transaminase enzymes, which are fundamental in the creation of GABA, dopamine, histamine and serotonin.[54] Research also suggests that vitamin B6 diminishes sympathetic output and acts peripherally to blunt the physiological impact of corticosteroids.[55]
  • Biotin (vitamin B7) is an important cofactor for the enzyme pyruvate carboxylase, which is involved in cortisol production.[56]
  • Vitamin C has involvement in dopamine production and is required for the activity of enzyme, dopamine β-hydroxylase (dβh), which requires vitamin C as a cofactor.[57]
Vitamin C is essential for HPA axis restoration. It plays a role in anxiolytic neuropeptide synthesis, glutamatergic regulation and attenuating oxidative stress.[58]

Vitamin C has been shown to lower anxiety symptoms in as little as two weeks, with one study demonstrating a reduction of 25.4% compared with placebo.[59],[60]

 

Additional Considerations

 

Restore essential fatty acid (EFA) status following chronic stress and increased inflammatory load:

High Purity, Low Reflux, Concentrated Fish Oil

Dosage: 5mL (1 tsp) daily or 2 capsules twice daily.

Omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to provide structural building blocks in brain membrane phospholipids, required for normal neuronal function, as well as reducing inflammatory load common to patients with anxiety.

Mechanism of Action/Clinical Research:

  • Omega-3 EFAs modulate BDNF levels by promoting neurogenesis.[61]
  • EPA and DHA have been found to increase neuronal growth in the hippocampus and cortical regions in vitro,[62] while also promoting neurotransmitter signalling,[63] reducing oxidative stress (thereby protecting neurons from apoptosis)[64] and shifting microglial polarisation towards an anti-inflammatory phenotype.[65]
  • DHA is essential for healthy synaptic function[66],[67]and is an important contributor to membrane fluidity of neuronal cells.[68]
  • EPA and DHA modulate the production of eicosanoids, cytokines and other factors such as peroxisome proliferator-activated receptors (PPARs), which regulate the inflammatory response.[69],[70],[71]EPA and DHA also attenuate NFκB activation, a transcription factor and master regulator of pro-inflammatory mediators including IL-1β and TNF-α.[72]

 

OR

Specialised Pro-Resolving Mediators[1]

Dosage: 1 capsule twice daily.

Specialised Pro-resolving Mediators (SPMs) to lower systemic and neuroinflammation, which contribute to anxiety and depression pathogenesis.

Mechanism of Action/Clinical Research:

  • SPMs, including resolvins, protectins and maresins, may assist with anxiety and depression via modulation of microglial behaviour.[73]

Microglia contain several receptors for SPMs and in vitro studies demonstrated resolvin (Rv) D1 and RvE1 shifted microglia from M1 phenotype into an anti-inflammatory phenotype.[74]

  • SPMs trigger the switch from the M1 to the M2 phenotype, therefore reducing inflammation and tissue damage, and promoting resolution,[75] which may be associated with neuroinflammation in bipolar.[76]

 

COMBINED WITH

Vitamin D3

Dosage: Take 0.25 - 1.0 mL (by measuring dropper) daily with food or take 1 - 4 capsules daily with food depending on pathilogy test results.

Vitamin D to provide neuroprotection and enhance neuronal survival against the depleting effects of microgliosis caused by persistent HPA axis activation.

Mechanism of Action/Clinical Research:

  • Inadequate levels of serum 25-hydroxy-vitamin D3 have been associated with anxiety and depression,[77] with the degree of deficiency correlated with the severity of anxiety symptoms.[78],[79]

Two studies demonstrated vitamin D3 supplementation, at doses of 50,000 IU weekly or fortnightly, significantly lowered inflammatory and oxidative markers in participants with anxiety after 12 and 16 weeks.[80],[81]

  • Vitamin D3 functions as a neurosteroid, playing a role in serotonin synthesis and degradation,[82] cerebral antioxidant enzyme activity and BDNF levels.[83] Therefore, ensuring adequate serum levels with Vitamin D may help offer protection against mental illness.[84]
  • Evidences has shown that vitamin D may have a neuroprotective effect on dopaminergic pathways in the adult brain by increasing the levels of tyrosine hydroxylase, which modulate dopaminergic processes.[85]

 

If presenting with symptoms of gastrointestinal dysfunction:

Glutamine & Boswellia (Bospure Boswellia) for Intestinal Integrity

Dosage: Add 2 level scoops (7.7 g) to 200 mL water twice daily with food, or as directed by your healthcare professional.

Anti-inflammatory herbs combined with nutrients to support and maintain healthy intestinal integrity, protect the gastrointestinal mucosa and assist overall gut health and function.

Mechanism of Action/Clinical Research:

  • Aloe has been shown to promote the rapid repair of damaged membranes in the gastrointestinal tract.[86]
  • Boswellic acid compound, AKBA, acts as a potent antibacterial against gram-positive pathogens, with an ability to disrupt the permeability barrier of microbial membrane structures. AKBA has also demonstrated an inhibitory effect against the growth of microbial biofilms, particularly the growth of staphylococcus-containing biofilms.[87]
  • Glutamine serves as a precursor for nucleotide synthesis in rapidly dividing cells such as intestinal cells, therefore supporting healthy cellular reproduction and decreasing intestinal permeability.[88]
  • Larch arabinogalactans act as a prebiotic, enhancing beneficial gut microflora such as bifidobacteria and lactobacilli. Arabinogalactans are fermented by intestinal bacteria to create short chain fatty acids, particularly butyrate, which acts as a fuel source for epithelial cells, thereby aiding their replication and integrity and supporting intestinal health and barrier function.[89]
  • Zinc is involved in the initial step of epithelial wound healing, a process called epithelial cell restitution.[90]
  • A primary function of vitamin A includes its role in cellular differentiation, where it acts as a transcription factor, supporting mucosal immunity via induction of Tregs and increased secretory immunoglobulin A (sIgA), which protect the mucosal barrier.[91]

 

If patient is both anxious and depressed:

BCM-95™ Turmeric & Saffron for Depression

Dosage: Take 1 capsule twice daily with food

BCM-95™ Turmeric and saffron to alleviate heightened neuroinflammation, HPA axis dysfunction and sympathetic drive, while also supporting mitochondrial function and increasing BDNF production for enhanced neurogenesis.

Mechanism of Action/Clinical Research:

  • Both saffron and turmeric have been found to inhibit the activity of inflammatory transcription factors including NFκB.[92] Saffron and turmeric also inhibit pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, all of which can affect synaptic plasticity and neurotransmitter metabolism.[93],[94]

A randomised, double-blind, placebo-controlled study involving 123 participants that were prescribed 500 mg/d of BCM-95™Turmeric combined with 30 mg/d of saffron revealed significant reductions in depression and anxiety symptoms after 12 weeks.[95]

  • Saffron’s active constituent, safranal, has also been shown to have anxiolytic and sedative effects via innervation of the GABAergic pathway.[96]

Saffron, at a mean dose of 30 mg/d, provided a large positive effect size when compared with placebo for anxiety and depression, and a selective serotonin reuptake inhibitor (SSRI) for depression in a meta-analysis.[97]

  • Turmeric’s curcumin constituent facilitates neurogenesis through enhancement of BDNF, preventing structural changes that impede synaptic plasticity.[98],[99],[100] Curcumin has been found to block stress-induced decreases in BDNF and its upstream transcription factor, cyclic adenosine monophosphate response element-binding protein (CREB), in the hippocampus and frontal cortex by attenuating oxidative stress and inflammation.[101]
  • Curcumin has been shown to increase oxygen consumption, enhance Krebs cycle and electron transport chain function, and promote mitochondrial biogenesis and ATP production.[102]
  • Turmeric activates glutamate decarboxylase (GAD), which converts glutamate to GABA.[103]

A randomised, double-blind, placebo-controlled study involving 123 participants that were prescribed 500 mg/d of BCM-95™Turmeric combined with 30 mg/d of saffron revealed significant reductions in anxiety and depressive symptoms after 12 weeks.[104]

 

If presenting with blood glucose dysregulation:

Cocoa, Cinnamon and Chromium for Metabolic Syndrome

Dosage: To support healthy blood glucose and emotional wellbeing- Take 1 tablet twice daily with food.

Antihyperglycaemic herbs and nutrients that moderate glucose uptake and metabolism via 5’adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma (PPARγ)/phosphatidylinositol 3’-kinase and protein kinase B (PI3K/Akt) pathways, while also stimulating insulin secretion.

Mechanism of Action/Clinical Research:

  • Cocoa polyphenols may assist in the maintenance of cellular redox states in pancreatic β-cell lines, thereby exerting a protective influence against β-cell dysfunction.[105]
  • Cocoa polyphenols, cinnamon,[106] chromium[107] and gymnema[108] may reduce fasting glucose and facilitate glucose uptake, in addition to downregulating markers correlated with diminished glucose transport.

A randomised clinical trial in 66 subjects with type 2 diabetes given 4.8 g/d of cinnamon found significant reductions in fasting glucose and glycosylated haemoglobin A1c (HbA1c) after 12 weeks of treatment.[109]

 

If presenting with symptoms of hyperthyroidism:

Herbal Support for Thyroid Health

Dosage: 1 tablet three times daily.

Herbal ingredients that regulate abnormal thyroid levels, reducing T3 and T4 concentrations that potentiate central nervous system overactivity and altered synaptic plasticity.

Mechanism of Action/Clinical Research:

  • Lemon balm exerts anxiolytic activity, which is attributed to an elevation of GABA levels via inhibition of GABA transaminase (an enzyme that metabolises GABA).[110]

A clinical trial involving stressed individuals with mild to moderate anxiety disorders and sleep disturbances were administered 600 mg/d of lemon balm 15 days. Results demonstrates an 18% reduction in anxiety manifestations, a 15% reduction in anxiety-associated symptoms, and 42% reduction in insomnia.[111]

  • Rehmannia and lemon balm influence thyroid hormones by inhibiting conversion of T4 to T3,[112],[113] with lemon balm further disrupting TSH binding to its receptor.[114]

 

Supportive Programs: Anxiety Panic Disorder Naturopathic Protocol

The Metagenics Shake It Practitioner Weight Management Program is designed to help patients comfortably transition from a hypercaloric diet to a hypocaloric diet, facilitating sustainable weight loss while also improving insulin sensitivity and optimising metabolic function. Given the association between mood disorders and cardiovascular disease, addressing any underlying metabolic drivers may improve brain function and associated symptoms.

The Metagenics Shake It Practitioner Weight Management Program is designed to help patients comfortably transition from a hypercaloric diet to a hypocaloric diet, facilitating sustainable weight loss while also improving insulin sensitivity and optimising metabolic function. Given the association between bipolar disorders and cardiometabolic diseases, addressing any underlying metabolic drivers may improve brain function and associated symptoms.

 

Diet and Lifestyle Recommendations: Anxiety Panic Disorder Naturopathic Protocol

Diet: 

  • Adherence to a Mediterranean diet is associated with lower incidences of anxiety, depression and psychological distress.[115]
  • The Mediterranean diet is inclusive of high intake of fruits and vegetables, lean protein, quality essential fatty acids, and whole grains (limiting starchy grains and vegetables).
  • Wholefoods containing large amounts of polyphenols have demonstrated various anti-depressant activities including[116],[117]:
Increasing hippocampal BDNF levels (resveratrol).
Lowering inflammation and modulating monoamine neurotransmission (fisetin from strawberries).
Increasing neuronal plasticity (proanthocyanidins from blueberries).
Modulating the HPA axis (green tea polyphenols).
  • Wholefood diets have also been found to increase hippocampal volume compared to ‘Western’ diets, which were associated with hippocampal atrophy.[118]
  • The Metagenics Wellness Diet reflects the whole-food principles of the Mediterranean diet and also provides a simple guide to moderate portion size and the overall balance of macronutrients.
  • The composition and function of the gut microbiota has been linked to anxiety and depression.[119] Fermented foods and prebiotic fibres can be used to improve intestinal health as they promote the expression of short-chain fatty acids (SCFA), anti-inflammatory cytokines and modulate the gut microbiota.[120]

Prebiotics, at 5 g/d for four weeks, have been shown to significantly improve anxiety symptoms in irritable bowel syndrome patients.[121]

  • Consuming low glycaemic index carbohydrates, avoiding refined carbohydrates and regular protein intake may assist with blood glucose stabilisation.
  • Reduce intake of dietary stimulants, including caffeine and alcohol.

Lifestyle:

  • Aerobic exercise has been shown to increase hippocampal levels of BDNF as well as hippocampal volume,[122],[123],[124] with increases in BDNF secretion occurring after an acute bout of exercise.[125]
  • Reduce physical symptoms of stress and anxiety through regular relaxation and exercise, including activities that involve progressive muscle relaxation and breathing control (yoga, Pilates, meditation) and cardio exercise. Thirty-minute sessions, three times per week are recommended.[126]
Applications such as Headspace provide access to guided meditations, including specific sessions that concentrate on anxiety, stress, sleep and focus.
Yoga practice produces beneficial outcomes for anxiety and depression. Results from systematic reviews and meta-analyses report a ‘large and statistically significantly reduction in anxiety symptoms,’[127] and ‘positive effect(s) on improving depressive symptoms.’[128]
  • Often patients with anxiety or panic disorder cease exercising because they misinterpret bodily sensations produced as worsening of their symptoms, such as increased heart rate, shortness of breath or sweating. This can be managed by careful explanation and encouraging gradual introduction of exercise.[129]
  • Emotional freedom technique (EFT), also known as tapping, is an evidence-based intervention that combines exposure and cognitive therapies with stimulation/percussion of eight acupuncture points.[130]
  • EFT decreases hyperarousal in the amygdala and hippocampus[131] and has been shown to regulate six genes associated with inflammation and immunity (i.e. downregulation of inflammation and upregulation of immunity),[132] as well as significantly reduce salivary cortisol within one hour.[133] EFT intervention appears to generate relevant changes in the neurochemistry sustaining the issue (e.g. the pain, cravings, anxiety).[134]
  • EFT has demonstrated efficacy for various physiological and psychological symptoms including anxiety,[135] depression,[136] post-traumatic stress disorder (PTSD),[137] pain and cravings.[138],[139] Treatment gains are also reported to persist over time.[140],[141]
  • Vagal nerve stimulation produces various benefits relevant to cognitive and mental health, including but not limited to increasing heart rate variability (HRV),[142] reducing inflammation[143] and increasing monoamines (norepinephrine, serotonin).[144]

Transcutaneous vagal nerve stimulation (tVNS) provides a non-invasive alternative, involving the use of externally applied devices to stimulate the vagus nerve, typically at the auricular branch on the ear (e.g. TENS device) or cervical branch on the neck (e.g. gammaCore device).

  • The Beyond Blue organisation can provide information and additional support to patients affected by anxiety, depression, substance abuse and additional mental health conditions.

 

Clinical Investigation and Pathology: Anxiety Panic Disorder Naturopathic Protocol

 Clinical Screening Rationale
Mood and Stress Questionnaire

A questionnaire designed to help Practitioners establish:

  • Levels of stress, anxiety and mood concerns, prioritised in relation to each other.
  • Appropriate treatment strategies based on common response patterns under stress and neurotransmitter patterns.
Depression Anxiety Stress Scales (DASS) A self-report questionnaire designed to measure the three related negative emotional states of depression, anxiety and tension/stress.
Blood Pressure

Monitor if patient is at risk of or presenting with cardiovascular complications.

  • Optimal reading: under 120/80 mmHg
  • Normal to high: over 120/80 mmHg and up to 139/89 mmHg
  • High: over 140/90 mmHg

 

  

Pathology Testing Ideal Reference Range Rationale
Cortisol Awakening Response Profile (CAR)

Cortisol waking: 8.0 to 18.0 nmol/L 

Cortisol waking +30min: 8.0 to 18.0 nmol/L

Cortisol waking +60min: 8.0 to 18.0 nmol/L

Cortisol profile, Total CAR: 23.0 to 42.0 nmol/L

A non-invasive saliva test that serves as a reliable marker of stress response. The CAR test measures the predictable rise and fall in cortisol within the first hour of awakening and can be used to evaluate the overall function of the HPA axis.
Adrenocortex stress profile

Cortisol morning: 6.0 to 42.0 nmol/L

Cortisol noon: 2.0 to 11.0 nmol/L

Cortisol afternoon: 2.0 to 11.0 nmol/L

Cortisol evening: 1.0 to 5.0 nmol/L

DHEA profile morning: 2.5 to 25.0 nmol/L

DHEA/cortisol AM: 0.20 to 0.60 ratio

Salivary cortisol and dehydroepiandrosterone (DHEA) testing is a non-invasive saliva test that evaluates bioactive levels of the body’s important stress hormones. This test examines four saliva samples over a 12-hour period for levels of cortisol and DHEA at 8 am, 12 pm, 4 pm, and 8 pm.
Serum TSH

Ideal range: 0.4 to 2.0 mlU/L

Subclinical hypothyroid: 2.0 to 4.0 mlU/L

Overt hypothyroid: <4.0 mlU/L

 

Ideal range for preconception/pregnancy-

Preconception: <2.5 mlU/L

First trimester: 0.1 to 2.5 mlU/L

Second trimester: 0.2 to 3.0 mlU/L

Third trimester: 0.3 to 3.0 mlU/L

Currently, TSH concentration is the most reliable indicator of thyroid status at the tissue level.
Serum fT4 10 to 25 pmo/L Considered to provide a reliable indication of true thyroid function.
Serum fT3 4 to 8 pmol/L Performed as part of a more comprehensive evaluation of thyroid function.
ESR

Female:

17 to 50 years: 3 to 12 mm/hr

>50 years: 5 to 20 mm/hr 

Male:

17 to 50 years: 1 to 10 mm/hr

>50 years: 2 to 15 mm/hr

Raised ESR may be indicative of acute inflammation and is often elevated in cardiovascular presentations.
Hs-CRP

Normal value < 10 mg/L

However, ideal is <1 mg/L

Raised CRP may be indicative of chronic inflammation and is often elevated in cardiovascular presentations.
Homocysteine 5 to 15 µmol/L A driver of cardiovascular disease and endothelial dysfunction.
Vitamin B12 Normal levels in adults and children: 120-680 pmol/L. Vitamin B12 is a key nutrient required for various cellular process, including methylation, DNA synthesis and neurotransmitter production.
Folate Normal levels in adults and children: 360-1,000 nmol/L Folate is a key nutrient required for various cellular process, including cellular division, methylation, DNA synthesis and neurotransmitter production.
Glucose (fasting) 3.5 to 6.0 mmol/L Assessment of hypoglycaemia.
Glucose (random) 3.5 to 9.0 mmol/L Assessment of hypoglycaemia.

   

Pharmaceutical Treatments: Anxiety Panic Disorder Naturopathic Protocol

  • Benzodiazepines: Benzodiapepines act as positive allosteric modulators on the GABAα receptor, facilitating inhibitory GABA neurotransmission and reducing excitability of neurons.[145]
  • Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs block the reuptake of serotonin in the presynapse from the synaptic cleft, increasing levels of serotonin in the brain.[146]

 

Additional Resources: Anxiety Panic Disorder Naturopathic Protocol

  • Depression Anxiety Stress Scales (DASS): A self-report questionnaire designed to measure the three related negative emotional states of depression, anxiety and tension/stress.
  • The E-Mental Health in Practice guide provides practitioners with an extensive list of evidence-based digital mental health resources.

 

Footnotes: Anxiety Panic Disorder Naturopathic Protocol

[1] Ensuring patients maintain an omega-3 index above 8% is essential to SPM production. Omega-3 status can be evaluated/monitored using the Omega-3 Index Test (refer to pathology testing section). In the instance of deficiency, consider co-prescribing High Purity, Low Reflux, Concentrated Fish Oil Liquid or Capsules.

 

References: Anxiety Panic Disorder Naturopathic Protocol

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