The Ecology of Mental Health

scott shannon, md abihm

Agenda

PhilosophyConcerns with psychiatry Assessment-Treatment formatDepressionAnxietyAddictions

What is Integrative Psychiatry?

It is the ecologically sound care of the whole person: body, mind and spirit*.

*mental, emotional, social or spiritual issues may predominate as presenting complaints

Integrative Psychiatry

Ecological in scopeIntuitive in cognitive styleScientific in frameworkHumanistic in approach to the patientDevelopmental in conceptCollaborative in practice

Ecological in scope

Person as ecosystemInterconnected and interdependentThe myth of narrow treatments Precautionary principleHomeostasis and stability

Intuitive in style

Intuition vs Logical thoughtPattern recognitionNon-linear and non-algorithmicLooking for imbalancesCan’t be forcedMindfullness and receptivity

Scientific in FrameworkUse of evidenced based approachesSafety vs efficacyThe limitations of RCTsCommercial biasLevel of Risk should determine cautionPower of placebo

Humanistic in approach

CaringRespectful SupportiveInspiration and motivationEmpowerment as crucial concept

Developmental in concept

We grow from one cell, we reach an incredible level of complexityWe are neuro-plastic and ever changing-the cns rewires as we goEpigenetics can make change lastIntegration as frontal lobe capacityNutrition, environment, familyIllness? or deficit of nutrient, skill or nurturing

Collaborative in practice

The need to listen and listen some moreNeed vs wantDecision making as real partnersProvide choices“The Empowered Patient”

Psychiatric Disorders

Complex PatternMulti-faceted causePower of Mind and SpiritRelational FoundationSelf-correcting PowerMental/Emotional/Spiritual Homeostasis

Mechanistic Assumptions

in PsychiatryComplex triggers often ignoredNarrow measures of efficacy and successAssumes isolation of effect Mind has no effect on brainTreatment is often narrowly focusedIgnores self-correcting capacityAssumes static/non-plastic CNSIgnores epigenetics

The Power of Epigenetics

The Human Genome Project has disappointedAffected 1 to 2% of psychiatric care at mostEpigenetic changes from diet, trauma, environment, can last years to generations-the Agouti MiceSwedish farmers and harvest

Challenged Assumptions

Psychiatric illnesses represent fundamental imbalances of brain biochemistryOur current psychiatric diagnostic system is valid or reliableOver the long term psychiatric medications are safe and effective treatmentsPsychiatric treatments other than psychopharmacology represent second tier options

Low Reliability

Large meta-analysis38 studies16,000 patientsLow correlation between clinical evaluations and standardized diagnostic interviews (SDIs)K value: 0.27 overall (poor)

Rettew, DC et al Int Methods Psych Res 2009, 18:169-184

STEP-BD Study of Bipolar Relapse

1,469 patients with Bipolar Disorder48.5% relapse within two yearsDepression more common than maniaLamotrigine better than antidepressants“Recurrence common and highlights the need for more treatment options”

Perlis, R, American Journal of Psychiatry 2006, 163:217-24

CATIE Study of Anti-Psychotics

Largest and longest study of its kindOver 1,400 patients with schizophrenia18 months: Tolerability and EfficacyEfficacy and Tolerability: poor74% stopped meds for any reasonSubstantial side effects: 64% to 70%FGA fared as well as Atypicals

Stroup, T and McEvoy, J. American Journal of Psychiatry 2006, 163: 600-622.

STAR*D Study of Major Depression

Largest US study of Major Depression.3,671 patients over one year.No medication better than another. 37% remission after 1 trial, 67% after 4.Massive drop out rates= 21, 30 and 42%More than one med= more likely to relapse“The 67% rate is almost certainly an over estimate of what would happen in the real world”

Rush, J, American Journal of Psychiatry 2006, 163:1905-17

Common Themes

Research not sponsored by pharmaceutical industryLooks at long term resultsDesigned to mimic clinical practiceOffers much more pessimistic view of medsHumbles us in psychiatry

Is Psychiatry Evidenced Based?

Does the current clinical practice of psychiatry follow evidence?The trend towards polypharmacy grows13,079 psychiatric visits monitored:1996-2006Visits with 2 or more psychiatric medications-increased from 42% to 60%Very little evidence to support this1.2 million children on 2 or more psych meds: even less evidence

Mojabai, R Arch Gen Psych 2010; 67: 26-36

Anti-Depressants and Depression Severity

Meta-analysis of RCTs from 1980 to 2009Effect size for mild to moderate depression : non-significantSeparation increases as depression severity increasesReaches significance at HDRS of 25 (very severe= 13% of depressed patients)Reinforces Kirsch’s prior articles

Fournier, JC et al JAMA 2010 303 (1): 47-53

Kirsch, I et al PLoS Med 2008 5(2): 45

Kirsch meta-analysis 2008

Publication Bias in Psychiatry12,564 patients and 74 FDA registered studies

reviewed31% not published94% of published trials positive (51% positive by FDA)37 positive published, 1 positive notVast majority of unpublished: negativeCompared FDA effect size to published: increase ranged from 11 to 69%, average distortion = 32%

Turner, E NEJM 2008, 17;358(3):252-60

Questions Long-Term Efficacy

Robert Whitaker-Anatomy of an Epidemic 2010

Safety, Efficacy and the Patient

RCTs highlighted as gold standard, highly scrutinizedSafety appears to be less severely scrutinizedSafety vs Effectiveness: a paradigmatic split----CAM vs ConventionalPatient preference should help to determine directionTrue informed consent rarely provided

Shannon, Weil, Kaplan Alternative and Complementary Therapies 2011,17 (2):84-91

Depression as a Model

Ecosystem: Environmental, physical, emotional, mental, social, or spiritual triggersFinal common pathwayLack of core pathophysiologyVery broad assessment needed

Depression—Overview

What is it? What heals it?Mood disorder spectrumCurrent treatment trendsVulnerability and resilience

The Six Realms

EnvironmentalPhysicalMentalEmotionalSocialSpiritual

Depression—Holistic AssessmentHistory (also collateral)PhysicalMental/EmotionalSpiritual

Depression—History

First onset—age, situationChronicity/severityResponse to treatmentHistory of traumaRelational historySpecific quality of experience

Assessment: Environmental

Time outside and sunlightChaotic settingsCommuteHeavy metalsPesticidesAir quality

Assessment: Physical

ExerciseEnergy/vitality/sexualityAppetite/diet/food allergyWeightSleep (also rule out sleep apnea)Physical illness/symptoms

Assessment: Lab

Thyroid: TSH, T3, T4 (antibodies?)Adrenal: DHEA-s, cortisol patternBlood: CBC/ferritinGI/dysbiosis and elimination dietVitamin D levelCholesterolHigh Sens CRPHomocysteine/MTHFR

Assessment: Emotional

Emotional regulationAffective expressionHistory of traumaFamily of origin

Assessment: Mental

Recreational/relaxationWorkHobbiesAddictions/patternsCreative outlet

Assessment: Social

Primary relationshipsFamily time/playFamily relationships/dynamicsFriends-type and varietyCommunity connectionNeighbors

Assessment: Spiritual

Worship/pathPrayerCenteringLove

Depression Treatments: Physical–1 Overview

ExerciseNutrition/oilsHerbs and supplementsEnergy medicineAcupunctureSomaticPharmacologyHormonal

Depression Treatments: Physical–2Aerobic Exercise: increases BDNF15-20 minutes4 times per weekLots of supportive/encouragement neededPrescribe itSMILE study: 10 months later 70% response vs. 48%. Relapse 8%v38%

Babyak, D Psychosomatic Medicine 2000 (62): 633-38

Depression Treatments: Physical–3Nutrition

High proteinFood allergy concernsCaffeine freeLow sugarOmega 3 oils—1,000 mg of EPA/day minimum (EPA/DHA better than flax)

Food Allergy

Colic or reflux as infantEczemaChronic otitis media; lots of anti-bxInsomniaIBS or chronic constipationMood issues/irritibilityNarrow food interest

Cookbook from the1940’s

EFA and Psychosis

Randomized, placebo controlled, DB 12 wk trialHigh risk group (sub-threshold psychosis) 13-25 years old-81 patients1.2 gm/d of omega 3 EFA for 12 weeksProgression to psychosis monitored over next 40 wks.Active: 4.9% vs 27.5% placebo

Amminger, GP et al, Arch Gen Psych 2010 67(2): 146-154

EFA in Pregnancy

Randomized placebo controlled DB trialEFAs in Pregnancy with MDDOne month washout, 8 week trial33 subjects (all female)3.4 grams Omega-3 EFAsSignificantly higher response rate (p=.03) and lower HAM-D (p=.001)

Su, KP et al, J Clinical Psychiatry, 2008 69(4): 644-51

Depression Treatments: Physical–4Herbs and Supplements

St. John’s Wort (0.3%)—600mg a.m./300mg p.m. (mild to moderate depression)5-HTP—50-400 mg/day–sedatingGinkgo Biloba—80-120 mg BID–stimulatingTonics (Ginseng/Ginger)B-6 and B-12- (B complex 50mg best)

Depression Treatments: Physical–5SAMé

S–adenosyl methionine (crucial methyl donor)Enhances methylation in bodyProfound, effective and synergistic antidepressantStimulating, works quickly (2 weeks)Headache, insomnia, nausea200-800 mg twice daily, start low, give on empty stomachCan induce mania

St. John’s wort

Common roadside plant

Traditional use for centuries

Few side effects (headache, nausea, rash)

Non-fatal in overdose

Three to four week onset of action

St John’s wort: Cochrane29 studies from a variety of countries

with 5,489 patients, randomized and double blind.

Major Depression only Placebo or antidepressants Superior to placebo in treating patients

with major depression and are "similarly effective" as standard antidepressants

Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database of Systematic Reviews 2008, 4. October

St. John’s wort: RisksCytochrome P450 effects-Decreases potency of:BCPcyclosporinedigoxinwarfarinprotease inhibitorsTheophyline

Increases potency of: MAOi, SSRI, Alcohol, triptans,

narcotics

St. John’s wort

Safe, effective treatment for depression (mild to major)

No Black Box warningUse quality product; 0.3%

hypericins is a general markerCost $8–20 per monthBID dosing best: 900mg/day

total, age 8 up

S-adenosyl-l-methionine (SAM-e)

B12 B12

Folate5MTHF + Homocysteine MethionineSAM-e

Methyl Donation DA

SAM-e 5HT

NE

SAMe in Depression

28 acceptable studies vs either antidepressants or placebosSuperior to placeboComparable or more effective than antidepressants Faster (1-2 weeks)Better tolerated, fewer side effects

AHRQ Reviews: (www.ahrq.gov/clinic/epcsums/samesum.pdf

Depression Treatments: Physical–6Energy Medicine

Light—10,000 lux, 18 inches, 30 minutes in the a.m. Dawn simulator also helpfulCranial electrical stimulationNegative ionsHomeopathy–Cochrane meta- analysis does not support

Depression Treatment: Physical–Acupuncture

Electro-stimulationMeta-analysis: 9 RCTs, 4 good quality“Odds ratios suggests some evidence for the utility….General trends suggests acupuncture as effective as antidepressants.” Sham looks similar

Leo, R et al J Affective Disorders 2007 (97): 13-22

Depression Treatments: Physical–8Hormonal Augmentation

Desiccated thyroid (1-2 grains in the a.m.)Cytomel (10-25 mg once or twice daily)DHEA Check DHEA sulphate blood level firstEstrogen/Testosterone

Arch Gen Psych. 2005;62:154-162 (90mg and 450 mg of DHEA for 6 weeks)

Depression Treatments: Physical–9Medications

SSRIsBuproprionVenlafaxineStimulantsIatrogenic CauseOther

Depression Treatments: Physical—10Somatic

Massage/RolfingQi GongCranial Manipulation (head injury, headaches)Reiki

Vitamin D and depressionVitamin D receptors exist in the brainLow level of serum 25-hydroxyvitamin D and high PTH are significantly associated with a high depression score (Jorde, 2005)25-hydroxyvitamin D3 and 1,25-dihydroxvitamin D3 levels are significantly lower in psychiatric patients than in normal controls (Schneider, 2000)Lowest Vit D in fibromyalgia assc with depression (Armstrong, 2007)

Vitamin D and Mood

RCT of 441 overweight pts in NorwayVit D levels less than 40 ng/ml= more depressionVit D supp with 20k or 40k IU/wk= significant reduction in BDI over 1 yr

Jorde R et al J Int Medicine 2008, 264(6): 599-609

Sunshine

Vitamin D deficiency is “a pandemic”Cause: tall buildings, unbanization, obesity, pollution, cars, sunblock, sun fear11 million in US with SADVitamin D deficiency found in many illnessesVitamin D improves serotonin levelsLevels drop significantly summer to winter

Holick, MF NEJM 2007 Jul 357 (3): 266-81 Veith, R Nutritional Journal 2004 Vol 13: 213-18 Zillerman, A British J Nutrition 2003 Vol 89 (5): 552-72

Light Therapy for Depression

TreatmentGet active and outside, midday bestTemper melanoma hysteriaMeasure Vit D levels: 25(OH)D not D3Target = 50-65 ng/ml not 30Use Cholecalciferol (D3) not ergocalciferol or calcitriolRDA: prob insufficient, should exceed 1,000iuIf mood disorder: Measure level, if low add 3,000 to 6,000 iu/day of D3 and retest in 6 wks.

Gloth, FM J Nutr Health, 1999 3(1):5-7

Treat Depression with Photons

Not just SAD alone: any depressed mood d/oEffective for pediatric SAD: RCTAs effective as 20mg of fluoxetine with fewer sides and faster onset. No blackbox warning10,000 Lux for 30 to 60 minutes in AM-earlyDawn simulation looks to be as good or better

Avery, DH et al Biol Psych 2001 50(3):205-16 Lam, RW et al Am J Psych 2006 163(5):805-12 Swendo, SE et al JAACAP 1997 36(6): 816-21

Depression Treatments: Mental PsychotherapyRecreationSocial/RelationshipsWorkHobbiesEducation

Depression Treatments: Mental–Therapies

Cognitive–BehavioralSolution OrientedDBT (Dialectical Behavior Therapy)Hakomi, Somatic Experiencing (body oriented)Meridian Therapies (Energy Psychology-EFT, etc)Groups

Depression Treatments: Spiritual

RetreatSpiritual CounselingDream WorkServiceExistential Exploration: meaning and life purposePrayerLove, Joy, Hope

Sample Protocol-Depression

Vitamin C 1,000 mgB complex 50 mg with Folate 1 mgEPA 1-2 gramsSAMe or SJW or SSRI based on pt preferenceInositol 3-6 grams bidHigh Protein dietExercisePsychotherapyInner workSunlight, Vit D (if needed) and nature

Anxiety

What is it? What heals it?Anxiety Disorder SpectrumDevelopmental ContextVulnerability and Trauma

Anxiety Treatments: BodySupplements and Herbs

St. John’s Wort (0.3%)—900 mg/dayCalcium/Magnesium glycinate 200-600 mg of Mag; 600-1,200 mg of Calcium per dayInositol—2 to 6 grams TIDL-theanine 200-400mg BIDValerian BID or qhs Melatonin—0.5 mg qhs

Anxiety Treatments: PhysicalNutrition

No caffeine and low sugarConsider gluten free trialComplex carbohydratesFood allergiesWatch additives/nutrasweet

Anxiety Treatments: PhysicalExercise

WalkingSwimmingYogaTai Chi

Anxiety Treatments: PhysicalSomatic

AcupunctureCranial manipulationCranial Electrical Stimulation (CES)MassageHot bathsYoga

Cranial Electrical Stimulation

First clinical trail in 1804Prescription device in USApproved by FDA and VALow level pulsed current between ears (less than one milliampere)40 clinical studies: 8 of them quality Safe and effective for anxiety

Klawansky, S J Nervous Mental Dis, 1995 183 (7): 478-84

Anxiety Treatments: PhysicalMedications

SSRIs – low doseBuspironeAvoid Benzo s beyond 6 wksBeta-blockers

Benzos

Problems with Benzos

Meta-analysis: 13 studies Cognitive decline noted on meds: ALL 12 areas of psychological evaluation 3 mos to 3 yrs AFTER withdrawal:

Significant cognitive decline noted in 5 areas: visual-spatial, attention and concentration, problem solving, general IQ, psychomotor speed.

Stewart, S J Clinical Psych 2005, 66: (2): 9-13

Inositol

Part of cell membranesFound in our foodIsomer of glucose: sugar alcoholNeeded for proper functioning of serotoninCSF of depressed patients=low inositolKey second messenger-relays info to nucleus

Inositol

Effective for depression [Evidence level A-RCT]Effective for panic [Evidence level A-RCT]Effective for bulimia [Evidence level B]Effective for OCD [Evidence level A-RCT]Not effective for schizophrenia, Alzheimer’s or ADHD [Evidence level A-RCT]

Inositol and Panic

Compared to placebo (sugars)RCT/cross-over; 21 completed study6 grams twice daily after washoutWell toleratedSignificant decrease in panics and phobias

Benjamin, J et al American J Psychiatry 1995 ; 152: 1086

Inositol and OCD

RCT of 15 patientsPlacebo vs 18 grams per day6 weeks each phaseSignificant improvement on inositolSubscale: Compulsions >> ObsessionsSSRI responders did wellResisters resisted again

Fux, M et al American J Psychiatry 1996; 153: 1219-21

Inositol in Panic

RCT-cross over/random order of 20 ptsFluvoxamine 150 mg vs. inositol 18 gramsInositol superior at 4 wks; equal at 9 wksInositol had fewer side effects

Palatnick, A et al J Clinical Psychopharmacology 2001 ; 21: 335-39

Inositol: UseSweet tasting powder-mix in any liquidWell toleratedDosing: 1 to 6 grams BID or TIDExcellent sleep aid or stress moderatorChildren love it

L-theanine

L-Theanine

Natural component of teaAnalog of glutamine and glutamateIncreases GABA and dopamine Promotes alpha waves/non-sedatingNeuroprotective and non-toxicDose: 100 to 800 mg/dayEvidence level: +

Haskell, R Biol Psychiatry 2008 77(2): 113-22

Clinical Actions of L-TheaninePromotes relaxation- described as a calm alert

without sedation (Ito 1998). Reduces stress-induced reactions in humans

(Kimura 2007).

Heart rate variability: reduced activation of the sympathetic nervous system (Kimura 2007).

Increased EEG alpha waves, consistent with relaxation (Ito 1998, Abdou 2006, Gomez-Ramirez 2007).

Enhances attentional functioning in humans (Gomez-Ramirez 2007).

Improves memory and learning in humans and animal models.

Trichotillomania

N-acetylcysteine seems to restore glutamate conc in nucleus accumbens12 week RCT of 50 peopleNAC: 1200 to 2400 mg (vs placebo)56% much or very much improved vs 16% (p= .001)9 weeks to initial improvement

Grant, JE et al Arch Gen Psych 2009; 66 (7): 756-763

Anxiety Treatments: Mental

BiofeedbackRelaxation TrainingBreath WorkMeditationEducationEMDR

Anxiety Treatments: Spirit

Faith vs. FearDeathRitualCenteringPrayerSpiritual Community

Sample Protocol-Anxiety

Inositol- 4 to 6 grams bid or tid5 HTP 50 to 200 mg tidRelaxation, meditation, walking, yoga, journalingPsychotherapy, EMDR if trauma L-theanine 200 to 400mg bid No caffeineIf obsessive: NAC 600-1200mg bid

NAC in schizophrenia

RCT of 140 pts-refractory schizophreniaAverage duration of 12 yearsNAC- 1,000 mg BID over 6 monthsSignificant benefit: negative symptoms, global function, abnormal movementsOther effects: better insight, self-care, social interaction and mood regulation.

Berk, M et al Biological Psychiatry 2008 ; 64: 361-368.

N-acetylcysteine (NAC)

Precursor of glutathione: most common and powerful antioxidant in bodyCrucial in detoxification processModulates dopamine and glutamateMultiple positive studies in addictionRCT (75 pts) in bipolar: + for depression- 1 gm bid over 6 months

Berk, M Biological Psychiatry 2008 ; 64: 468-475

Addictions—Overview

NutritionAcupunctureEEG BiofeedbackAA/NAExercise

Addictions: Nutrition

High proteinAvoid sugar, simple carbohydratesTaper off caffeineEFA = (1-2 gm of EPA/DHA/ daily)

Addictions: Supplements Detox Period B Complex—50-100 mg of each in a.m. and p.m.Vitamin C (ester)—1,000 mg 2 or 3 times a dayZinc—20 mg twice dailyCal/Mag (Citrate)—400/200 mg 3 times a dayInositol—4 gm two or three times dailyMelatonin—0.5 to 2 mg qhsFree form amino acids 4 to 6 caps AC TID

Addictions: Acupuncture

Michael Smith, MD–Lincoln Hospital, Bronx500,000 plus treatments there4 needles in each ear NADA protocol, 200 plus facilitiesReduces cravings and recidivismHazleton and Hennepin County, MN

Bullock, ML Lancet; 1989 24:1435-1439

Addictions: Summary

Coordinated, combined treatment criticalBill W’s three legged stool—Body, Mind, SpiritSupport, inspire and confront

Sample Protocol-Addictions

Acupuncture B complex 50 mg in am, Vit C 1,000 TID, Cal/Mag 500/250 TID, 4 to 6 caps of free form amino acids TID and Inositol 4 to 6 grams TID ExerciseHigh Protein, low sugar, low carb dietLoose the caffeine

Summary

People are unique and multi-dimensionalEducation, support and motivation are invaluableAvoid simple solutions and one-dimensional thinkingStrive for balance and harmonyEmbrace the complexity and potential in each personLove yourself and those you serve

Scott Shannon, MD ABIHMWholeness Center

2620 E Prospect Rd. #190

Fort Collins, Colorado 80525

970.221.1106 scott@wholeness.com

www.wholeness.com

Micronutrient Supplementation in Young Adult Prisoners

RCT in 231 young offendersBroad array of minerals, vitamins, EFA’sActive group—26.3% fewer rule violationsActive group—35.1% fewer violent acts

Gesch et al (Oxford), British Journal of Psychiatry, 2002, 181:22-28

Multivitamins and Mood

Placebo controlled trial of 129 adults for one yearQuarterly psychological testing10x DRI of 9 vitaminsAt 12 months hostile subscale significantly improvedMood status related to thiamine (B1) riboflavin (B2) and pyridoxine (B-6)statusThe delay in results suggests resolution of chronic nutritional deficiencies is responsible

(Benton et al, Neuropsychology 32:98-105, 1995)

Multivitamins and Mood

Randomized placebo controlled trial of 80 adultsB vitamins, calcium, magnesium, zinc (12x DRI)Within 28 days—significantly lower anxietyDepression scores significantly improvedPerceived stress significantly lower

(Carroll et. al. Psychopharmacology 150:220-225, 2000)

Multivitamins and Mental Health

8 week placebo controlled trial of 1081 menCompared mood, cognitive factors: MVI vs. placeboDeficiency levels = increased irritability, nervousness, fear, depressionSignificant improvement only in deficient group

(Hesker et. al. Annals NY Academy of Science 669:352-357, 1992)

Multivitamins and Mental Health

Baseline Vit C deficiency when supplemented = significantly reduced depression, anxiety and mood labilityBaseline folate deficiency = significantly improved mood lability, concentration, self-confidence, extroversion and moodConclusion: nutritional status is correlated with psychological functioning and that even slight deficiencies, if chronic, can result in clinically significant impairment

(Hesker et. al. Annals NY Academy of Science 669:352-357, 1992)

ReferencesDepression

Apparent fish consumption and the prevalence of major depression: a cross-national perspective[letter]. Lancet 1998;351:1213.Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early and late onset alcoholics. Biol Psychiatry 1998;44:235-42.A replication study of violent and non-violent subjects: CSF metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol Psychiatry 1998;44:243-9.

ReferencesMore on Omega-3 Fatty Acids in Depression

Low plasma concentrations of DHA predict low CSF levels of 5-hydroxyindolacetic acid.

A marker of brain serotonin turnoverSuch low concentrations are strongly associated with depression and suicide

World Rev Nutr Diet 82:175-86, 1996

ReferencesSt. John’s Wort

Shelton, RC and Keller, MB Effectiveness of St. John’s Wort in Major Depression, JAMA 2001; 285: 1978-86Linde, K. et al., St. John’s Wort for Depression–Overview and Meta-analysis, Br.Med. J. 1996; 313: 253-8Hypericum Depression Trial Study Group: Effects of Hypericum in Major Depressive Disorder, JAMA 2002; 287: 1807-14

References SAMe

Bressa, GM, SAMe as Antidepressant: Meta-analysis of Clinical Studies. Acta Neurologica Scand. 1994; 154: 7-14

Kagan, BL, et al: Oral SAMe in Depression. Am. J. Psychiatry, 1990; 147: 591-595

References 5–HTP

Angst, J., et al, The Treatment of Depression with 5–HTP Arch. Psychiatrica Nerv. 1977; 224: 175-186

Turner, S., Tryptophan and 5—HTP for Depression, Cochrane Database Syst. Review, 2002 (1): CD003198

Burley, WF, et al, 5—HTP: A Review of its Anti-depressants Efficacy and Adverse Effects, J. Clin. Psychopharmacology, 1987 (7), 127-137.

References Kava–Kava

Volz, H.P. and Kieser, M. Kava–Kava Extract in Anxiety Disorders, Pharmacopsychiatry, 1997, Jan.; 30(1): 1-5

Pittler, M.H. and Ernst, E., Kava Extract for Treating Anxiety, Cochrane Database Syst. Review, 2003 (1): CD003383.

Boerner, R.J. et al, Kava–Kava Extract in Generalized Anxiety Disorder, Phytomedicine, 2003; (10) 4: 38-49

Schulze, J. et al, Toxicity of Kava Pyrones, Phytomedicine, 2003; (10) 4: 68-73.

References Inositol

Levine, J., Controlled Trials of Inositol in Psychiatry, European Neuropsychopharmacology, 1997, May; 7 (2): 147-155

Palatnik, A. et al, Double-Blind, Controlled, Crossover Trial of Inositol vs. Fluvoxamine for the Treatment of Panic Disorder, J. Clinical Psychopharmacology, 2001; 21: 335-339

Gelber, D. et al, Effects of Inositol on Bulimia, Int. J. Eating Disorders, 2001, April; 29(3): 345-8

Levine, J. et al, Double-Blind, Controlled Trial of Inositol Treatment of Depression, Am. J. Psychiatry, 1995, May, 152(5): 792-4.

Fux, M. et al, Inositol Treatment of Obsessive-Compulsive Disorder, Am. J. Psychiatry, 1996, Sept.;153(9)

Resources

Emmons, H., The Chemistry of Joy Simon and Schuster: NYC, 2006Kemper, K., Mental Health, Naturally AAP: Elk Grove, Il, 2010Lake, J and Spiegel D Complementary and Alternative Treatments

in Mental Health Care APPI: Washington DC, 2007.Lake J Textbook of Integrative Mental Health Care Thieme Medical

Publishers: NY, 2007Larsen, J. Seven Weeks to Sobriety Ballentine Books: NY 1997Logan, A., The Brain Diet Cumberland House: Nashville TN, 2007Murray, M., Encyclopedia of Nutritional Supplements, Prima Press:

NY 1996Pizzorno, J. and Murray, M., Encyclopedia of Natural Medicine,

Prima Press: NY 1997Ratey, J., Spark: Exercise and the Brain Little, Brown: NYC, 2008Shannon, S., Handbook of Complementary and Alternative

Therapies in Mental Health, Academic Press: San Diego, CA 2002

Zuess, J., The Wisdom of Depression, Harmony Books: NY 1998

Resources

Nordic Naturals (Pro EPA), 1-800-662-2544 ext. 102www.nordicnaturals.comOmega Brite (Hi EPA), 1-800-383-2030www.omegabrite.comPharmax (Frutol), 1-425-467-8054www.pharmaxllc.comSynergy (EM Powerplus), 1-888-878-3467www.truehope.com

Scams

Urinary Neurotransmitter TestingMLMsChelation?

Scams

Urinary Neurotransmitter Testing

Aggressively promoted Three major companiesTest: urinary metabs: Serotonin, E, NE, Dopamine, Glutamate, Glycine, Taurine, etc

Recent IFM Debate

Chip Watkins, MD FP, Chief Medical Officer, Sanesco

Jay Lombard, MD Neurologist, Assistant Professor-

Cornell Medical SchoolTopic: what is the value of UNT

testing

Chip Watkins’ points

It is an accurate and reliable testWe are testing a complex systemWe should be testing the brainA variety of studies show changes with UNT and psychiatric illnessMany people improve with testing and treatment

Jay Lombard’s Points

No relationship between serotonin in CNS and urine5-HIAA research not clear, quite conflicting biomarker in psychiatryNot clear what high or low 5-HIAA meansDopamine extremely complex in CNSNE has some correlation in urine, but phenotype is so obvious testing is just not neededIf you want to test: cortisol males more sense

Other Points

These companies provide conflicting advice with same dataNIH research: RCT, 84 patients No difference between depressed patients and controls: HVA/5-HIAAThese companies sell proprietary products linked to their testing

Mixed Effect on ExcretionPrevious studies (small) gave mixed

results824 healthy individualsGiven doses of up to 2700 mg of 5-HTP and 17 grams of Tyrosine (up to qid dosing)No correl with 5-HTP and urine serotonin1671 data points: 390=inverse relationship and 375=no changeResponsive group: 150 to 900 mg (Cont..)

Tyrosine

Consistent suppression of dopamine with supplementation across dose rangeMajority of both neurotransmitters synthesized in kidney or gut. (95% or more from outside brain)No value to test UNT prior to treatment

Trachte, GJ et al Neuropsychiatric Disease and Treatment 2009:5 227-35

Summary

Patient Response to oral loading: 1/3 up. 1/3 same. 1/3 down

“The uncoupling of NT excretion from the ingestion of precursors is most likely caused by the degradation of blood born NT in the kidney. Most of the serotonin or dopamine found in the urine is made by the kidney.”

Scams

Urinary Neurotransmitter TestingMLMsChelation?