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

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.

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

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?

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

Process: Communication Skills

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

Standard approach

• Diagnose• Provide diagnosis-specific treatment

• Challenges• Making a diagnosis; what if they don’t meet

criteria?

• Mastering medications

Wissow and Gadomski, 2008

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

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

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

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.

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

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

Content: Conventional

• Psychotherapy• Medications

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

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

SSRI Side effects 1

• GI upset• Headache; sleep

disorders• Sexual side effects

Dizziness, Fatigue, Sweating

• Neonatal withdrawal syndrome

• Drug interactions

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

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

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!

Integrative Approach

• Lifestyle – Environment, Exercise/Sleep, Nutrition, Mind-Body

• Supplements• Massage• Acupuncture

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

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

Light Therapy for Depression

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

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)

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)

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

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

Exercise as Therapy – Yes

Lawlor DA. BMJ 2001

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

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!

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)

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)

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

Omega 3 EFA’s: mechanism

• Neuronal membrane structure and function

• Brain development• Second messenger inside cells

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)

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

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!

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

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

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?

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

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

Bottom line on Amino acids andB vitamins

• Healthy diet rich in green vegetables and nutritious protein sources

• Consider B-complex supplement

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)

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

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

Non-dairy sources of calcium

• Soy beans, tofu

• Calcium fortified OJ

• Green leafy vegetables (broccoli)

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

Lifestyle: Stress management

• Stress is common• Stress commonly triggers mood problems• Managing stress: exercise, sleep, nutrition,

mind/emotion/body/spirit– Meditation– Biofeedback

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

Stress, Emotion, and Physiological Activation

High Arousal/High Energy

SYMPATHETIC

PARASYMPATHETIC

Low Arousal/Low Energy

Stress, Emotion, and Physiological Activation

High Arousal/High Energy

SYMPATHETIC

PARASYMPATHETIC

Low Arousal/Low Energy

Negative

Emotion

Positive

Emotion

“Fight-or-Flight”

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

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

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

After lifestyle and stress management, what?

• St. Johns’ wort• Massage• Acupuncture

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)

Herb- drug interactions: SJW

Speeds elimination of many drugs: digitalis,

theophylline, clarithromycin, erythromycin,

protease inhibitors and OCPs

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)

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?

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

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

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?

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

Goal-setting

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

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?

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

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)

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!

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!

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

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?

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).

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?

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!

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

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/