Complementary meds for migraines and depression

Potential triggers of migraine

- Stress

- Poor sleep

- Excessive amount of caffeine or alcohol

- Fasting

- Fatigue

- Weather

- Hormonal

- Auditory, olfactory

- Alcohol

Feverfew (tanaxetum parthenium) Migraine and MoA

A herb rich in sesquiterpene lactones, parthenolide

Inhibits 5-HT release from platelets = excessive 5HT in pathophysiology

Inhibits COX and LOX = ↓ inflammation

Feverfew evidence

Possibly effective in reducing frequency, low quality evidence

Feverfew dose

50-150 mg d for up to 4 months

Feverfew Adverse Effects

Well tolerated.

Mild reversible AE

Long term: GI sx, mouth ulceration

Chewing leaves: Contact derm, sore mouth, lip swelling, dizziness, stiff joint, headache, weight gain, menstrual change

Feverfew cautions

Not recommended in pregnancy and BF

Contra indicated in < 18 (hypersensitivity)

Magnesium MoA

In migraine, Deficiency in pts/ during attacks = CSD, altered neuro transmitter release, platelet hyper-aggregation

MOA

NMDA receptor - role in controlling vascular tone, reactivity to endogenous hormones and neurotransmitters

Magnesium evidence

Possibly effective in ↓ frequency and intensity - maybe in Mg deficiency only

Effective in preventing menstrual migraine

Magnesium dose

300-600 mg d for upto 3 months

Magnesium Adverse Effects

Diarrhoea, gastric irritation

Inorganic preparations >350 mg/d may be associated with AE

Magnesium Contraindications

Heart block

Renal failure

Overuse of Mg OH/SO4 = other deficiencies

Riboflavin (B2) Migraine MoA

Water soluble B vitamin . Component of Flavin coenzymes: PAD, FMN. Dietary or intestinal bacteria sources.

Improves mitochondrial energy metabolism

Important for ATP production - mitochondrial deficit in pathophysiology

Riboflavin Evidence

Possibly effective in ↓ frequency

Doesn't reduce pain severity/duration

SR probably effective prophylaxis

Riboflavin Dose

200-400mg d for 3-4 month

Riboflavin AE and toxicity

Diarrhoea, polyuria, anaphylaxis (rare)

No toxicity for 400mg d

Co-enzyme Q10 Migraine MoA

Endogenous enzyme cofactor

Role in energy metabolism, oxygen utilisation in brain/muscles

Antioxidant against migraine inflamm markers

↓ cytokine and MMP9 expression

Important in mitochondria ETC

Both pro and anti-coagulant effects

Co-enzyme Q10 Evidence

Possibly effective in ↓ frequency and duration

Possibly prevention

Paediatric: ↓ frequency + severity

Co-enzyme Q10 Dose

150-300mg d

Paediatric: 1-3mg/kg/d (liq cap)

Co-enzyme Q10 AE

<1% (>200mg d): Dizziness, nausea, epigastric discomfort, anorexia, diarrhoea, photophobia, irritability, skin rash

Diet for depression

Features:

- Higher intake of fruit, vegetables, nuts

- Lower intake of pro-inflammatory food: processed meat, trans fat)

- Alcohol in moderation

- High quality fats

Lifestyle:

- Diet, sleep, exercise

- Role in depression aetiology, progression, and treatment

Association with depression:

- Confers some protection against depression

- Prevents diet-induced 'damage' to the brain: oxidative stress, insulin resistance (med diet = low GI = slow release of sugar = ↓ insulin resistance), inflammation, vascularization changes

- Higher intestinal barrier integrity - inflammatory theory important in pathogenesis

- Correlation between functioning of digestive, nervous, and immune system

- Gut microbiota involved in tryptophan metabolism, 5HT synthesis, BDNF levels

St Johns wort MoA

MOA: Modulate 5-HT, DA, NE effects, may inhibit reuptake

St Johns wort Dose

Dose: 600-1800 mg d

St Johns wort Interactions

CYP3A4 and p-glycoprotein inducer

Do not combine with standard treatment

SSRI/SNRI: risk of serotonin syndrome

St Johns wort Safety

Bipolar: mania induction

Photosensitivity

Potential issues of quality and standardisation

No pregnancy or BF

St Johns wort Evidence

Monotherapy +++

Likely as effective as mild-mod standard anti-depression treatment

Curcumin for depression

- MOA: Anti-inflammatory - comorbid inflammatory disorders

- Adjunct/monotherapy ++

- Safety issues: hepatoxicity

- Pregnancy/ BF: likely unsafe

Considerations:

- Formulations with sufficient bioavailability advised - liposomal forms

Saffron (Crocus sativus) for depression

Evidence:

- adjunct/monotherapy: ++

Dose: 30 mg od-tds

Safety:

- Minor AE: GI, increase perceived mental stimulation

Consideration:

- Quality and standardisation of extracts essential (expensive)

Folic/ Folinic acid, methyl folate (depression)

MOA

- Folate: B9 from diet

- Needed for DA, NA, 5-HT synthesis, cognitive function

Adjunct therapy ++, not for monotherapy. Potential extra benefit if raised inflammation, obesity, pregnancy.

Dose: methylfolate 15 mg d

Interactions:

- Anticonvulsants (phenytoin)

- MTX (separate by 24h)

- SSZ (↓ folic acid)

- Warfarin, Anticoagulants

- Fluorouracil (↑ AE/toxicity)

Safety

- Fair

- Large doses of synthetic folic acid linked to slight increase in some cancers

Considerations

Higher risk of deficiency:

- Pregnant or childbearing age

- Alcoholics

- Malabsorption (CD, coeliac)

- MTHFR polymorphism

Zinc (sulfate or hydroaspartate) (depression)

MOA

- Anti- inflammatory

- Neuro/ Immunological- modulating

Deficiency: increase proinflammatory cytokines +altered 5-HT function

Adjunct ++

Specialised use in comorbid low immunity,oxidative stress, inflammation

Dose: 25 mg d

AE

Long term use -> Cu deficiency -> anaemia

Lozenges: dry mouth, GI, burning, nausea, dizziness

Intranasal: permanent loss of smell - advise against use

Interaction:

- Coffee (separate by 4h)

- NSAID, tetracycline, quinolone (separate by 3h)

Safety:

- Caution with higher doses

- Nausea on empty stomach. Chelations more absorbable

Higher risk of deficiency populations:

- Pregnant/ BF

- Alcoholics

- Vegetarians

- Sickle cell disease

> 6 months infants breastfed

Vitamin D (depression)

MOA

- Increase expression of genes encoding tyrosine hydroxylase (DA and NE synthesis)

Adjunct +. Potential extra benefit in winter

Dose: 1500IU -4000IU d

AE

> 275 mcg/ d = hypercalcaemia, vascular calcification

Small daily/weekly doses

High risk of deficiency pt:

- Housebound/ avoids sun

- Dark skin

- Clothing that covers skin

- Malabsorption

- Meds that breakdown vitamin D (some epilepsy meds)

Omega 3 (EPA) (depression)

MOA

Antidepressant activity - modulates NE, DA and 5-HT activities + enhanced glutathione antioxidant capacity

- Inadequate dietary intake + imbalance of O-6:O-3 EFAs associated with depression

Adjunct: +++

Not for Monotherapy - possibly if raised inflammation, obesity, dietary deficiency

Dose

- 1-2g EPA adjunct

Up to 4g d if raised inflamm markers

Interactions: Anticoagulants

Quality may be an issue

Encourage dietary fish + EPA supplementation

Probiotics (depression)

Adjunct: ++

Monotherapy: + (weekly dosing)

Dose: Lactobacillus and Bifidobacterium spp 1-10billion units d

Optimal strains not confirmed - likely affected by genetics, diet, microbiome