Natural Therapies for Adolescent Depression: Do they work Are they safe

1
Natural Therapies for Adolescent Depression Do
they work Are they safe

• Kathi J. Kemper MD FAAP
• Caryl J Guth Chair for Holistic and Integrative
  Medicine
• Author The Holistic Pediatrician
• Wake Forest University School of Medicine

2
Faculty Disclosure

• In the past 12 months I have had no relevant
  financial relationships with the manufacturers of
  any commercial products and/or providers of
  commercial services discussed in this CME
  activity. I do not intend to discuss an
  unapproved or investigative use of a commercial
  product or device in my presentation.

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Objectives (by the end of this session you will
be able to)

• Define the role of patient-centered communication
  for adolescent depression visits
• Describe the importance of a healthy lifestyle
  and the safety and effectiveness of dietary
  supplements in promoting healthy moods.
• Refer patients to evidence-based resources for
  additional information about lifestyle and
  complementary therapies to promote mental health

4
Depression Case

• A 17 year old girl who is sad has had a drop in
  grades recently broke up with her abusive
  boyfriend less interested in participating in
  band has stopped taking her SSRI after hearing
  about black box warnings.
• Her only medications are oral contraceptives.
• Will St. Johns wort help (the news reports are
  very confusing)
• How do you advise her

5
Management Issues

• Process (communication skills)
• Content (focus on healthy lifestyle if its good
  for the heart its probably good for mood)
• Speed (baby steps)
• Resources

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Process Communication Skills

• Standard approach
• Patient-centered care
• Health promotion focus

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Standard approach

• Diagnose
• Provide diagnosis-specific treatment
• Challenges
• Making a diagnosis what if they dont meet
  criteria
• Mastering medications

Wissow and Gadomski 2008
8
Parental expectations

• Dont believe they are effective change agents
• Have prior beliefs about what will help
• Want help but afraid of what you might say
• Want empathy but expect child is the agenda

Wissow and Gadomski 2008
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Adolescent Expectations

• Here to be fixed or punished
• Not used to having a substantive role in visit
• Uncertain about confidentiality
• Different agenda than parent
• Incomplete and stigmatizing views of mental
  health

Wissow and Gadomski 2008
10
Physician Expectations

• Will be presented with insoluble problems
• Double drowning everyone will leave more
  hopeless and/or angry than they started
• Will lose control of time

Wissow and Gadomski 2008
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Evidence-based skills

• Agenda setting
• Engaging both child and parent
• Prioritizing specific concerns goals define
  success
• Problem formulation and solving
• Finding reasons to hope and first steps to
  solutions
• Framework health promotion and stress management
• Time management
• Managing rambling and interruptions
• Promoting hope and confidence
• Diagnosing and Advice giving
• Avoiding and managing resistance

Pediatrics 2008 Feb121266-75.
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Finding a common agenda

• Commitment to eliciting it from both parent and
  child/youth
• Setting up and enforcing turn-taking
• Respecting confidentiality
• Encouraging and modeling the ability to talk in
  front of each other

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Crude 6-month change in child clinical measures
as a function of change in providers
patient-centeredness
Change in SDQ symptom score
Change in SDQ impact score
p
p.015 adjusted for baseline function
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Content Conventional

• Psychotherapy
• Medications

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Cognitive Behavioral Therapy

• From an evidence-based perspective
  cognitive-behavioral therapy is currently the
  treatment of choice for anxiety and depressive
  disorders in children and adolescents.
• Compton SN. JAm Acad Child Adolesc Psychiatry.
  2004

16
Conventional Treatment Rx

• TCAs - no evidence of efficacy in pre-pubertal
  children
• SSRIs - no overall evidence of efficacy in
  pre-pubertal children
• SSRIs marginally better than placebo in teens
  with MDD Prozac OK for teens by FDA
• SSRIs are HELPFUL in OCD and anxiety disorders
  even in pre-pubertal children
• Safer DJ. Pediatrics 2006 118 (3) 1248

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SSRI Side effects 1

• GI upset
• Headache sleep disorders
• Sexual side effects Dizziness Fatigue Sweating
• Neonatal withdrawal syndrome
• Drug interactions

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SSRI Side effects 2

• Serotonergic syndrome (HTN tachycardia mania)
• Agitation and hostility
• Suicidal ideation esp in those with
  agitation/hostility
• Review of 22 RCT pediatric with 9 antidepressant
  drugs.
• 2298 patients with active drug 1952 with
  placebo
• Serious suicidal adverse events
• 78/2298 versus 54/1952
• Incidence rate ratio 1.89 (95 CI
  1.18-3.04)
• Mosholder AD. J Child Adolesc Psychopharmacol.
  2006

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Psychiatric Meds in kids

• Little science of long term safety
• 1.6 million kids on 2 or more meds science
• Neurological and hormonal impact mostly unknown

20
Content natural therapies

• Depression is one of the top 10 diagnoses for
  which patients seek natural therapies
• Commonly used among depressed adolescents
• Fewer than 30 of depressed teens tell docs they
  are using natural therapies
• Clinicians need to ask!

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Integrative Approach

• Lifestyle Environment Exercise/Sleep
  Nutrition Mind-Body
• Supplements
• Massage
• Acupuncture

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Lifestyle - overview

• Environment More Sunshine Less TV
• Exercise/Sleep (more of both)
• Nutrition (Essential nutrients for optimal brain
  function EFA amino acids vitamins minerals)
• Mind-Body Therapies manage stress
• Meditation
• Biofeedback

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Sunshine circadian rhythms and sleep

• Desynchronization of internal rhythms plays an
  important role in the pathophysiology of
  depression.
• Resetting normal circadian rhythms can have
  antidepressant effects.
• Winter depression was first modeled on
  regulation of animal behavior by seasonal changes
  in day length and led to application of light as
  the first successful chronobiological treatment
  in psychiatry.
• Fuchs E. Int Clin Psychopharmacol 2006
• Wirz-Justice A. Int Clin Psychopharmacol. 2006

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Light Therapy for Depression

• Plus 3 studies not included in this review
  comparing dim light to bright light. Golden R. Am
  J Psychiatry. 2005

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Light therapy

• Proven effective for SAD (Terman M Evid Based
  Ment Health 2006)
• Meta-analysis of studies from 1987-2001 (effect
  size0.53 95 CI0.18 to 0.89 similar to
  medications) for non-SAD
• RCT of 29 women with non-seasonal depression
  light therapy for 28 days significantly better
  than control (McEnany GW 2005)

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Light Therapy 2

• Benefits onset within 2 days effective in
  institutionalized elderly and community
  effective in summer and winter
• Side effects hypomania autonomic
  hyperactivation
• (Terman M 2005)

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Turn off Depressing TV

• Respondents who repeatedly saw people falling or
  jumping from the towers of the World Trade
  Center had higher prevalence of PTSD (17.4) and
  depression (14.7) than those who did not (6.2
  and 5.3 respectively).
• Depressive symptoms after the hurricane were
  predicted by watching television coverage of the
  looting that occurred in New Orleans
• Ahern Psychiatry 2002
• McLeish. Depress Anx 2008

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Lifestyle 2 Exercise

• Depressed mood / fatigue are common in those
  deprived of usual exercise.
• Mood changes noted in patients with injuries and
  mono.
• Changes over time in kids exercise/gym/playground
  time
• Exercise benefits depression
• Common sense precautions

Berlin AA. Psychosomatic Med 2006
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Exercise as Therapy Yes
Lawlor DA. BMJ 2001
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Yoga for depression

• Five RCTs --each used different forms of yoga.
• All trials reported positive findings
• No adverse effects except fatigue and
  breathlessness
• Pilkington K. J Affective Disord 2005

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Lifestyle 3 Sleep

• Poor sleep is barometer of depression
• Reduced sleep equals impaired focus and labile
  mood (ADHD Learning problems)
• Sleep quality is a good screen for good mental
  health in pediatric population
• We sleep 20 less than we did 100 yrs ago
• Promote healthy sleep!

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Lifestyle 3 Sleep Hygiene

• Regular time Routine
• Hot bath cool room dark room
• Massage before bed
• Lavender chamomile melatonin
• No caffeine within 8 hours of bedtime
• Music calm orderly quiet
• NO TV IN BEDROOM
• NO vigorous exercise right before bed
• GET MORE versus intentional sleep
  reduction/deprivation (in those with excessive
  sleep)

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4 Nutrition essential nutrients for optimal
brain function

• Omega-3 fatty acids
• Amino acids (SAM-E Trp 5-HTP)
• Vitamins (B vitamins Vitamin D)
• Minerals (Iron Calcium Magnesium Zinc)

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Omega-6 Fatty Acids
Omega-3 Fatty Acids
Linoleic Acid (182n-6)
a-Linolenic Acid (183n-3)
-6 Desaturase
(GLA) -Linolenic Acid (183n-6)
Stearidonic Acid (184n-3)
Elongase
(DHGLA) Dihomo--Linolenic Acid (203n-6)
Eicosatetraenoic Acid (204n-3)
-5 Desaturase
Eicosanoids
(AA)Arachidonic Acid (204n-6)
(EPA) Eicosapentaenoic Acid (205n-3)
Elongase
245n-3
Eicosanoids Leukotriene 5-series Prostaglandins
E3 Thromboxanes A3
-6 Desaturase
Eicosanoids Leukotriene 4-series Prostaglandins
E2 Thromboxanes A2
246n-3
ß-Oxidation
(DHA) Docosahexaenoic Acid (226n-3)
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Omega 3 EFAs mechanism

• Neuronal membrane structure and function
• Brain development
• Second messenger inside cells

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Mood and Omega-3s

• Inverse correlation between fish intake and
  depression (Hibbeln Lancet 1998 3511213
  Crowe Am J Clin Nutr 2007)
• Effective for bipolar patients (Stoll Arch. of
  Gen. Psych. 1999 56 407-12)
• Effective for major depression (Nemets Am. J.
  Psych. 2002 159 (3) 477-9)
• Effective for depression in Children ( Am J
  Psychiatry 20061631098-0)

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Fish Oil Doses Safety Brands

• Dose 1 gram daily of EPA probably enough.(Peet
  M 2002) Frangou S. Br J Psychiatry 2006)
• Safety fish allergies taste belching very
  high doses increased risk of bleeding
  nosebleeds Little risk of mercury dioxin
  PCBs
• Brands Compare brands at www.consumerlabs.com
• My family takes Coromega Carlsons or Nordic
  Natural
• Read labels Omega 3 does NOT necessarily all
  equal EPA/DHA

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Amino Acids SAM-E

• Produced from ATP and methionine
• Low folate can lead to low levels
• Meta-analysis SAMe significantly improves
  depression comparable to antidepressant
  medications (http//www.ahrq.gov/clinic/epcsums/sa
  mesum.htm)
• In an open trial of 30 adults with MDD for whom
  antidepressant meds ineffective SAM-E led to
  significant improvements in 50 and remission in
  43 (Alpert 2004)
• All tested products approved by ConsumerLab buy
  on sale!

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SAM-E Doses duration products

• Dose 800 1600 mg daily (adult)
• Benefits appear within 2-4 weeks of starting
  daily use
• Problems poorly absorbed (need enteric coating)
  mania in bipolar patients interactions with SSRI
  meds see http//www.consumerlabs.com/results/sam
  e.asp
• http//www.umm.edu/altmed/ConsSupplements/SAdenosy
  lmethionineSAMecs.html

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Amino Acids 5-HTP and L-tryp

• Acute tryp depletion leads to depression
• Dietary L-tryp - 5-HTP - serotonin
• Meta-analysis 5-HTP and L-trp better than
  placebo for depression (Shaw K Cochrane. 2002)
• Food sources dairy eggs poultry meat soy
  tofu nuts WHEY protein

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L-tryp doses and side effects

• Doses - start at 50 mg TID max dose 1200 mg
  daily
• Side effects EMS related to contaminated lot
  from one manufacturer nausea drowsiness May
  potentiate SSRI medications decreased
  carbohydrate intake and weight loss

42
Vitamin B6 - pyridoxine

• Low levels of pyridoxal phosphate (PLP) are
  associated with depressive symptoms (Hvas AM
  2004)
• Dose 100 200 mg daily benefits PMS-
  depression Odds ratio 2.(Wyatt KM. BMJ 1999)
• Side effects nausea vomiting abd. pain
  anorexia headache somnolence lower B12 levels
  sensory neuropathy (typically with doses over
  1000 mg daily can occur lower)
• Food Beans nuts legumes fish meat

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Folate and B12

• Folate
• Lower levels of folate in depressed persons
• Low folate associated with poorer response to
  antidepressant meds
• Supplemental folate can improve response to meds
• B12
• Lower levels in depressed persons

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Bottom line on Amino acids andB vitamins

• Healthy diet rich in green vegetables and
  nutritious protein sources
• Consider B-complex supplement

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Vitamin D and depression

• Vitamin D receptors in brain
• Low level of serum 25-hydroxyvitamin D and high
  PTH are significantly associated with depression
  (Jorde 2005)
• 25-hydroxyvitamin D3 and 125-dihydroxvitamin D3
  levels are significantly lower in psychiatric
  patients than in normal controls (Schneider
  2000)
• RCT of 44 Australian patients (none 400 IU
  versus 800 IU vitamin D) vitamin D3 significantly
  enhanced mood (Landsdowne 1998)

46
Mood and Minerals Iron

• Iron deficiency associated with depression
• Correcting iron deficiency helps with mood and
  attention
• Beard JL. J Nutr 2005
• LE Murray-Kolb. Am J Clin Nutr 2007

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Mood and Minerals Calcium

• Lower levels of calcium in depressed persons
• Higher PTH in depressed persons
• Estrogen regulates calcium and PTH metabolism
  sometimes dysregulates (Thys-Jacobs S. J Am Coll
  Nutr 2000)
• Supplementation may benefit women with
  PMS-related depression (Dickerson LM. Am Fam
  Physician 2003)
• 1000 1200 mg daily

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Non-dairy sources of calcium

• Soy beans tofu
• Calcium fortified OJ
• Green leafy vegetables (broccoli)

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Nutrition Summary

• Healthy fat (omega 3) not fried foods saturated
  fats
• Healthy protein (essential amino acids)
• Foods rich in minerals and vitamins (vegetables
  beans grains)
• Multivitamin-mineral supplement
• Fish oil supplement
• Consider SAM-E B vitamins Calcium
• Iron if deficient

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Lifestyle Stress management

• Stress is common
• Stress commonly triggers mood problems
• Managing stress exercise sleep nutrition
  mind/emotion/body/spirit
• Meditation
• Biofeedback

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Meditation

• Meditation training left-sided anterior
  activation a pattern associated with positive
  affect in meditators compared with the
  nonmeditators
• No RCTs specifically on depression though
  positive effects on anxiety
• Few side effects can combine mindfulness with
  CBT
• Davidson RJ Psychosom Med 2003

52
Stress Emotion and Physiological Activation
High Arousal/High Energy SYMPATHETIC
Low Arousal/Low Energy
PARASYMPATHETIC
53
Stress Emotion and Physiological Activation
High Arousal/High Energy SYMPATHETIC
Fight-or-Flight
LOW PERFORMANCE
HIGH PERFORMANCE
Negative Emotion
Positive Emotion
Low Arousal/Low Energy
PARASYMPATHETIC
54
Stress Emotion and Physiological Activation
High Arousal/High Energy SYMPATHETIC
Fight-or-Flight
Frustration Anger Hostility
Exhilaration Passion
Fear Worry Anxiety
Joy Happiness
Judgment Resentment
Love Care
LOW PERFORMANCE
HIGH PERFORMANCE
Feeling Overwhelmed Anguish
Kindness Appreciation
Negative Emotion
Positive Emotion
Hopelessness Submission
Compassion Tolerance
Despair Depression
Acceptance Forgiveness
Burnout Withdrawal Boredom Apathy
Serenity Inner Balance Reflection Contentment
Low Arousal/Low Energy
PARASYMPATHETIC
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Stress management biofeedback

• HRV biofeedback appears to be a useful adjunctive
  treatment for the treatment of MDD
• Significant improvements in
• Hamilton Depression Scale (HAM-D)
• Beck Depression Inventory (BDI-II) by week 4
• Karavidas et al. Appl Psychophysiol Biofeedback.
  2007
• Nolan RP. Am Heart J 2005

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Promote Social Support

• Religiosity (participation) helps protect against
  depression
• Participation in extracurricular clubs helps
  protect teens against depression
• Participation in organized athletics is
  protective
• Ongoing volunteer work is protective
• Connected people are happier people

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After lifestyle and stress management what

• St. Johns wort
• Massage
• Acupuncture

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Saint Johns wort

• Most commonly used CAM therapy for depression
• Comparable to sertraline in German RCT of 241
  depressed adults (Gastpar. Pharmacopsychiatry
  2005)
• 2 open label trials in teens showed improvement
  within 2 weeks in 25/33 and 9/11 patients
  (Findling 2003 Simeon 2005) Improvement in 2
  weeks predicts long-term response if no benefit
  in 2 weeks stop
• Current evidence regarding hypericum extracts is
  inconsistent and confusing different products
  used in different trials different kinds of
  patients in some studies St. Johns wort is as
  effective as standard medications but no more
  effective than placebo. (2005 Cochrane review)

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Herb- drug interactions SJW

• Speeds elimination of many drugs digitalis
  theophylline clarithromycin erythromycin
  protease inhibitors and OCPs

60
SJW safety

• Other side effects - photosensitivity
  serotonergic syndrome
• Product variability see www.consumerlabs.com
  Gaia Kira Sundown Natures Bounty
• Products used in POSITIVE TRIALS Laif 900
  (German STW3-VI) LI160 (Kira) WS5572 WS5570
  (Perika by Natures Way)
• St. Johns wort patient handouts are available
  from
• University of Maryland Medical Center
• Wake Forest University Baptist Medical Centers
  Best Health internet site (www.besthealth.com)

61
Massage

• Increased blood flow and lymphatic drainage
  Muscle relaxation Stress reduction
• Balances R L prefrontal cortex activity in
  those with right dominance (Jones N Adolescence.
  1999)
• Decreased levels of cortisol and increased levels
  of serotonin and dopamine in depressed adults
  (Field T. Int J Neurosci. 2005)
• In depressed pregnant women massage compared
  with progressive relaxation led to higher
  dopamine and serotonin levels and lower levels of
  cortisol and norepinephrine (Field T. J Psychosom
  Obstet Gynaecol. 2004 )
• Who volunteers

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Acupuncture

• RCT of 30 patients BDI scores fell from baseline
  by 16.1 points in the intervention group versus
  6.8 points in the sham controls (P(Acupunct Med. 2005)
• Meta-analysis the effect of electroacupuncture
  similar to antidepressant medication(Mukaino Y
  Acupuncture Med 2005).
• Good safety profile. Rare infections broken
  needles forgotten needles bleeding bruising

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Depression SUMMARY 1

• Listen to patients and families
• Negotiate clear goals and agreements
• Support healthy lifestyle including sunshine
  sleep exercise nutrition (supplement when
  necessary) and stress management

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Depression SUMMARY 2

• Correct deficiencies of B vitamins and minerals
• Consider supplements of fish oil SAM-E 5-HTP
• Consider safe therapies including massage and
  acupuncture
• Beware of potential interactions e.g. Saint
  Johns wort
• Be PRACTICAL How

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How Behavioral Pediatrics

• Identify the goal
• Consider various strategies
• Pick a strategy
• Identify a small achievable step that the
  patient and family can support
• Explore pros and cons of change
• Anticipate barriers identify resources
• Plan rewards/celebrations!
• Re-evaluate take the next step

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Goal-setting

• Pick a POSITIVE goal
• E.g. healthier lifestyle.

67
Example Healthier lifestyle

• To promote
• Better mood
• Better focus or concentration
• Greater calm More resilience
• More cheerfulness Greater adaptability
• More confidence More creative
• More clarity
• Better memory
• More harmonious relationships
• Higher self esteem
• More consistent with personal values
• other

68
Pick a specific strategy

• More exercise
• Better nutrition
• Judicious use of supplements
• Better sleep
• Healthier environment
• Stress management biofeedback journal
  meditation
• Use medication
• Massage psychotherapy acupuncture or other
  professional help

69
Identify a small achievable step

• Rome was not built in a day habits are not
  changed overnight BABY STEPS.
• For exercise go from sedentary to 5 minute
  walks with the dog 5 days a week.
• Be specific (with or without an MP3 player with
  or without a parent regardless of weather
  distance vs. time)

70
How important is this to you

• 0 1 2 3 4 5 6 7 8 9 10
• Not Very
• Why did you pick that number and not a lower
  number (e.g. a 7 instead of a 5)
• Asking this question helps the patient/family
  provide their own rationale for why this is
  important. They talk themselves into it!

71
How confident are you that you can do this for
one month

• 0 1 2 3 4 5 6 7 8 9 10
• Not Very
• If they pick an 8 or higher (pretty confident)
  proceed with next step of making a chart and
  planning rewards and follow-up.
• If they pick a number less than 8
• What would it take for you to go from the number
  you picked to a higher number Begin to explore
  their ambivalence. Its OK to be ambivalent
  about change!

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Identify Pros and Cons
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Identify Barriers and Resources

• In addition to (cons listed above) what other
  barriers or challenges might you anticipate as
  you try to make this change Need new tennis
  shoes need leash need pooper-scooper
• What resources do you have/need to help you make
  this change Will Mom commit to getting new
  shoes leash etc. Will the child want/need a
  reminder Is it helpful for Dad to do that Do
  they need a chore chart A calendar

74
Plan celebrations/rewards

• Pick a tangible reward and timing (will it be
  offered after week 1 2 3 4)
• Samples extra time with mom or dad extra phone
  minutes new walking shoes get to pick vegetable
  for dinner! get to pick family movie stickers
  for younger kids money for older kids
  controversial in some families. Support the
  family and child choices.
• Emphasize the importance of the
  reward/celebration. If the family says they
  expect good behavior suggest they consider
  celebrating it (instead of rewarding it).

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Sample behavior diary (OK to copy)
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Follow Up

• Follow- up in 4-6 weeks.
• Ask family/child to bring chart and say you plan
  to be proud of them (build expectation of
  success) and will ask them what theyd like to do
  for next step (involve them in problem solving).
• Do it!

77
Behavioral Pediatrics

• Identify the goal
• Consider various strategies
• Pick a strategy
• Identify a small achievable step that the
  patient and family can support
• Explore pros and cons of change
• Anticipate barriers identify resources
• Plan rewards/celebrations!
• Re-evaluate take the next step

78
Resources

• Kemper KJ Shannon S. Complementary and
  alternative medicine therapies to promote healthy
  moods.Pediatr Clin North Am. 2007
  Dec54(6)901-26
• Motivational Interviewing Preparing People to
  Change by Miller and Roznik
• Natural Medicines Comprehensive Database
• Natural Standards
• http//www.besthealth.com/IntegratedMedicine/