Natural Therapies for Adolescent Depression: Do they work? Are they safe?
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Natural Therapies for Adolescent Depression:
Do they work? Are they safe?Kathi J. Kemper, MD,
FAAPCaryl J Guth Chair for Holistic
and Integrative MedicineAuthor, The Holistic
PediatricianWake Forest University School
of Medicine
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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…):
1. Define the role of patient-centered communication for adolescent depression visits
2. Describe the importance of a healthy lifestyle and the safety and effectiveness of dietary supplements in promoting healthy moods.
3. Refer patients to evidence-based resources for additional information about lifestyle and complementary therapies to promote mental health
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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?
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Management Issues
• Process (communication skills)• Content (focus on healthy lifestyle; if it’s
good for the heart, it’s 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 don’t meet
criteria?
• Mastering medications
Wissow and Gadomski, 2008
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Parental expectations
• Don’t 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
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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 confidenceDiagnosing and Advice giving
• Avoiding and managing resistance
Pediatrics 2008 Feb;121:266-75.
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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 provider’s patient-centeredness
Change in SDQ symptom score Change in SDQ impact score
p<.0001 adjusted for baseline symptoms 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
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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
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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 size=0.53, 95% CI=0.18 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, 2002McLeish. 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 (18:2n-6) a-Linolenic Acid (18:3n-3)
(GLA)γ -Linolenic Acid (18:3n-6)
(DHGLA) Dihomo-γ-Linolenic Acid (20:3n-6)
(AA)Arachidonic Acid (20:4n-6)
EicosanoidsLeukotriene 4-series
Prostaglandins E2
Thromboxanes A2
Eicosanoids
Stearidonic Acid (18:4n-3)
Eicosatetraenoic Acid (20:4n-3)
(EPA) Eicosapentaenoic Acid (20:5n-3)
24:5n-3
24:6n-3
(DHA) Docosahexaenoic Acid (22:6n-3)
EicosanoidsLeukotriene 5-seriesProstaglandins E3
Thromboxanes A3
∆-6 Desaturase
Elongase
∆-5 Desaturase
Elongase
∆-6 Desaturase
β-Oxidation
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Omega 3 EFA’s: mechanism
• Neuronal membrane structure and function
• Brain development• Second messenger inside cells
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Mood and Omega-3’s• Inverse correlation between fish intake
and depression (Hibbeln: Lancet 1998; 351:1213; 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 2006;163:1098-0)
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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, PCB’s;
• Brands: Compare brands at www.consumerlabs.com
• My family takes Coromega, Carlson’s 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/samesum.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/same.asp
• http://www.umm.edu/altmed/ConsSupplements/SAdenosylmethionineSAMecs.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?
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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 1,25-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)
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Mood and Minerals: Iron
• Iron deficiency associated with depression
• Correcting iron deficiency helps with mood and attention
Beard JL. J Nutr, 2005LE 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
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Stress, Emotion, and Physiological Activation
High Arousal/High Energy
SYMPATHETIC
PARASYMPATHETIC
Low Arousal/Low Energy
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Stress, Emotion, and Physiological Activation
High Arousal/High Energy
SYMPATHETIC
PARASYMPATHETIC
Low Arousal/Low Energy
Negative
Emotion
Positive
Emotion
“Fight-or-Flight”
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Stress, Emotion, and Physiological Activation
High Arousal/High Energy
SYMPATHETIC
PARASYMPATHETICLow Arousal/Low Energy
Negative
Emotion
Positive
Emotion
“Fight-or-Flight”Frustration, Anger, Hostility,
Fear, Worry Anxiety
Judgment, Resentment,Feeling Overwhelmed, Anguish
Hopelessness, Submission,Despair, Depression
Burnout, Withdrawal,
Boredom, Apathy
Exhilaration, Passion,
Love, Care,
Joy, Happiness
Kindness, Appreciation
Compassion, Tolerance,Acceptance, Forgiveness
Serenity, Inner Balance,
Reflection, Contentment
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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. 2007Nolan 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
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SJW safety
• Other side effects - photosensitivity, serotonergic syndrome
• Product variability; see www.consumerlabs.com: Gaia, Kira, Sundown, Nature’s Bounty
• Products used in POSITIVE TRIALS: Laif 900 (German STW3-VI); LI160 (Kira), WS5572; WS5570 (Perika by Nature’s Way)
• St. Johns wort patient handouts are available from:University of Maryland Medical CenterWake Forest University Baptist Medical Center’s Best Health internet site (www.besthealth.com)
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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<0.001) (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.
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Example: Healthier lifestyleTo promote
Better moodBetter focus or concentrationGreater calm More resilienceMore cheerfulness Greater adaptabilityMore confidence More creativeMore clarityBetter memoryMore harmonious relationshipsHigher self esteemMore consistent with personal valuesother?
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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
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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)
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How important is this to you?
0 1 2 3 4 5 6 7 8 9 10Not 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!
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How confident are you that you can do this for one month?
0 1 2 3 4 5 6 7 8 9 10Not 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…. It’s OK to be ambivalent about change!
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Identify Pros and Cons
PRO CONChange More cheerful Change routine
More fit and cool Brother might tease
Clothes fit better Yucky dog clean up
Better sleep
Better self-esteem
No Change Easy Continued mood probs
Mom does yucky job Get fat
Feel ugly
Sleep badly
Unhappy with myself
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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?
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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)
Goal Sample: M T W Th Fri Sa Su TotalWalk dog 5 minutes 5 days a week √ √ √ √ √ 5Week 1 Week 2 Week 3 Week 4
Re-evaluate.Celebrate.Next steps?
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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 they’d like to do for next step (involve them in problem solving).
• Do it!
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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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Resources• Kemper KJ, Shannon S. Complementary and
alternative medicine therapies to promote healthy moods.Pediatr Clin North Am. 2007 Dec;54(6):901-26
• Motivational Interviewing: Preparing People to Change by Miller and Roznik
• Natural Medicines Comprehensive Database• Natural Standards
• http://www.besthealth.com/Integrated+Medicine/