Pediatric Depression from an Pediatric Depression from an Inte - PowerPoint PPT Presentation

Pediatric Depression from an Pediatric Depression from an Inte Integrative grative Pe Perspe rspective ctive scott shannon, md faacap university of colorado

Agenda — Our current situation — New ways of thinking — Depression — Treatment options — Bipolar and Ketamine

Unanticipated Consequences

New York Times Lead Story: April 7, 2018

Depression as a Model Depression as a Model — Environmental, physical, emotional, mental, social, or spiritual triggers — Final common pathway — Lack of core pathophysiology — Very broad assessment needed — Unique expression of imbalance

New ways of thinking New ways of thinking

A new wilderness to navigate

Overweight Children in US CDC 20% 20% 15 15% 10 10% age age 6 6-1 -11 age 1 age 12-1 -19 5% 5% 0% 0% 71 71-74 76 76-80 88-9 88-94 99-00 99-00 200 2001- 1- 2003- 2003- 02 02 04 04

IL-6 IL-6 Pre Predicts late dicts later illne r illness ss — 4,500 children assessed age 9 and again at 18 years old (ALSPAC). — Measured IL-6. Broken into thirds — High group 2x as likely to develop depression or schizophrenia — Higher levels associated with risk in dose-dependent manner Khandaker, GM JAMA Psychiatry 2014 Aug 13 epub 1332

Does inflammation change psychiatric outcomes? — Etanercept (Enbrel) improved MDD more than placebo in psoriasis study Tyring 2006 — — Adjunctive aspirin speeds response time to SSRI (fluoxetine) for depression phenotype in rats Mendlewicz 2006 — — Adjuctive celecoxib (Celebrex) improves outcomes to SNI (reboxetine) for MDD Muller 2006 — — In animal models, cytokine antagonists and anti- inflammatory drugs block depression phenotype after immune activation. — Dantzer 2008

Contributors to inflammation • Abnormal microbiome • Trauma = ACEs: inflammation via SNS activation • Stress • Obesity or metabolic syndrome • Diet, SAD, GMOs, HFCS, sugar • Toxic burden, amalgam fillings, organic pollutants • Infections • Intestinal permeability (leaky gut) • Injury, surgery

Decreasing Inflammation Decreasing Inflammation • Diet – loose weight and eat well – Mediterranean, Anti Inflammatory Diet for Dummies, New Atkins Diet, low carb diet. • Exercise – reduces cortisol levels • Meditation and other mind/body therapies • Supplements – Omega 3 Fatty Acid, 2G daily – Ashwaganda, 500mg bid – N Acetyl Cysteine, 1G bid – Vitamin D, 5,000iu/day • Medications – Statins, TCAs, Lovaza (Omega 3)

Mitochondrial Modulation Mitochondrial Modulation — CNS function places huge demands on energy production — There is increasing recognition that mitochondrial dysfunction may play a critical role in major psychiatric illness — Symptoms of mito dys: anxiety, mood d/o, cognitive dysfunction, psychosis and OCD — Studies correlate anxiety with mitochondrial abn in hippocampus Anglin RE Transl Psychiatry 2012 November 13

Mitochondrial Modulation Known Modulators: — 1. N-acetyl Cysteine (NAC) — 2. Acetyl-L-Carnitine — 3. S-adenosyl Methionine (SAM-e) — 4. CoQ10 — 5. Alpha-Lipoic Acid — 6. Creatine Monohydrate — 7. Melatonin Nierenberg AA Aust NZ J Psychiatry 2012, June 18

Huge in US: athletes and body builders

Buff up the Buff up the Brain? Brain? — Creatine monohydrate (CM) used to build muscle mass — Creatine Kinase (CK) plays key role in energy metabolism — Serum CK fluctuates with mood, depression and bipolar phase — May be gender differential-only female rats respond — 3-5 gm q am Allen PJ Neuroscience Biobehavioral Review 2012, 36 (5): 1442-1462.

Creatine in Teens — Pilot study with creatine for augmentation and MRI spectroscopy comparison with controls — 5 teen girls with TRD who failed fluoxetine — 4 grams daily for 4 weeks — Mean CDRS fell from 69 to 30 — A significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up Kondo, D J Affective DO 2011 135 (0): 354

Peds: Exercise for Depression — Meta-analysis: 50 studies (89, 894 pts). 2000-15 — Mean effect size: Significant ( r = -0.14; 95% confidence interval [CI] = -0.19 to -0.10) — Stronger effect sizes: measures of frequency and intensity of physical activity versus intensity alone Korczak, D et al Pediatrics 2017, 139 (4).

Chronotherapeutics — RCT of 62 adolescents (13-18 yrs) with moderate to severe depression — Compared bright light therapy vs wake therapy — BLT effective for mood at two weeks post intervention — No added benefit with WT to mood — Sleep quality improved in both groups Gest, S et al Eur Child Adol Pyschiatry 2016 Feb;25(2):151-61

Cookbook from the1940 ’ s

St John t John ’ s wort: Cochrane s wort: Cochrane l 29 studies from a variety of countries with 5,489 patients, randomized and double blind. l Major Depression only l Placebo or antidepressants l Superior to placebo in treating patients with major depression and are "similarly effective" as standard antidepressants Linde K, et al Cochrane Database of Systematic Reviews 2008, 4. October

Systemic Review of SJW vs Antidepressants Apayden, E et al, Syst Rev 2016; 5(1): 148 .

St. John’s wort: Risks Cytochrome P450 effects- Dec Decrea eases es potency of: l BCP l Cyclosporine l Digoxin l Warfarin l Protease inhibitors l Theophyline Incre Increase ases potency of: MAOi, SSRI, Alcohol, triptans, narcotics

St. John’s wort l Safe, effective treatment for depression (mild to major) l No Black Box warning l Use quality product; 0.3% hypericins is a general marker l Cost $8–20 per month l BID dosing best: 900mg/day total, age 8 up

SAM-e in Depression SAM-e in Depression

About the same as SSRI

SAM-e SAM-e — S–adenosyl methionine (crucial methyl donor) — Enhances methylation in body — Safe and synergistic antidepressant — Stimulating, works quickly (2 weeks) — Headache, insomnia, nausea — 200-800 mg twice daily, start low, give on empty stomach — Can induce mania

Saffron Saffron

Saffron (crocus sativus) Saffron (crocus sativus) — Greek frescos depict Saffron as medicine 3600 years ago — Herbalists: antispasmodic, thymoleptic, carminative, cognition enhancer, aphrodisiac, and emmenagogue. — Stigma and petals both studied — 15 mg-30mg twice daily used in all studies

Saffron in Depression and Anxiety — Systemic Review and Meta-analysis — 23 RCTs — Large effect sizes Depression (0.99); Anxiety (0.95) — Augmentation helpful: (1.23) — Concern: possible publication bias and regional concern Marx, W Nutrition Revi ew 2019 May 28. pii: nuz023

Depression Treatments: Depression Treatments: Mental/Emotional Mental/Emotional — Psychotherapy-indiv and family — Recreation — Social/Relationships — Work — Hobbies — Education

Depression Treatments: Depression Treatments: Spiritual Spiritual — Retreat and Nature — Spiritual Counseling — Dream Work — Service — Existential Exploration — Prayer — Love, Joy, Hope

Support Energy Support Energy — Adaptogens-Rhodiola: 2-400mg/am — Acetyl L Carnitine: 1-2,000mg/d — CoQ 10: 100-200mg/d — B Complex 50 mg in am — Vit C: 500-1,000mg BID — Think gut and candida — Explore sleep, think apnea

Catalysts for Profound Change — Retreat — Calamity — Psychedelics — Shamanic journey — Spiritual conversion — World travel/pilgrimage — Near death experiences (NDE) — Major events: birth, illness, divorce and death

Depression: tools — Supplements — Cognitive work (CBT/DBT) — CES — Gut/ Food Allergies — Exercise — Diet — Acupuncture — Family/Couples work — Hormones — New job/career — Light — Spiritual work — Medications — Animals/pets — Meditation — Mitochondria — Heavy metals removal — Herbal remedies

Assessment: Lab Assessment: Lab — Thyroid: TSH, T3 and T4 — Adrenal: DHEA-s & salivary cortisols — CBC/ferritin and Cholesterol — B-12 and folate — GI/dysbiosis: elimination diet — Vitamin D — Homocysteine — High Sens CRP — MTHFR

Depression-opinion what to avoid — Over emphasizing the physical — Over emphasizing medications — Getting stuck in a narrow path — Forgetting psychotherapy — Forgetting family dysfunction — Adding medications to medications

Depression: opinion what to do — Evaluate all ecosystems — Explore and support diet and sleep fully — Exercise — Supplements: SAM-e, SJW, Vit C, Saffron, Rhodiola, etc. — Low energy-diet/gut, adrenals or mitochondria — Explore sleep fully — Rule out inflammation and toxic overload — Address software and family issues — Inspire the patient to make changes

Opinion: Depression Opinion: Depression — SJW or SAMe or Saffron based on patient — B Complex 50mg (B-6 and 1 mg methylfolate) — EPA: 1 gram or more — Vitamin C: 500-1,000 mg — Exercise — Higher protein, high quality diet — Consider mitochondrial modulation or adaptogen if energy concern — Psychotherapy or education — Light therapy/sunlight

Bipolar Disorder in Kids — Previously extremely rare — Increasing rates— 40 fold rise in Dx in 10 yrs — Cultural, nutritional roots — Omega 3 oil deficiency=inflammatory CNS? — ADHD 80-90% co morbid — Anxiety, hallucinations, suicidality common Moreno, C. Archives Gen Psychiatry September 64 (9) 2007