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.

3. 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 it’s good for the heart, it’s probably good for mood) • Speed (baby steps) • Resources

6. Process: Communication Skills • Standard approach • Patient-centered care • Health promotion focus

7. Standard approach • Diagnose • Provide diagnosis-specific treatment • Challenges • Making a diagnosis; what if they don’t meet criteria? • Mastering medications Wissow and Gadomski, 2008

8. 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

9. 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

11. 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 Feb;121:266-75.

12. 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

13. 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

14. Content: Conventional • Psychotherapy • Medications

15. 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

17. SSRI Side effects 1 • GI upset • Headache; sleep disorders • Sexual side effects Dizziness, Fatigue, Sweating • Neonatal withdrawal syndrome • Drug interactions

18. 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

19. 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!

21. Integrative Approach • Lifestyle – Environment, Exercise/Sleep, Nutrition, Mind-Body • Supplements • Massage • Acupuncture

22. 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

23. 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

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

25. 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)

26. 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)

27. 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

28. 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

29. Exercise as Therapy – Yes Lawlor DA. BMJ 2001

30. 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

31. 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!

32. 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)

33. 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)

34. Omega-6 Fatty Acids Omega-3 Fatty Acids Linoleic Acid (18:2n-6) a-Linolenic Acid (18:3n-3) ∆-6 Desaturase (GLA)γ -Linolenic Acid (18:3n-6) Stearidonic Acid (18:4n-3) Elongase (DHGLA) Dihomo-γ-Linolenic Acid (20:3n-6) Eicosatetraenoic Acid (20:4n-3) ∆-5 Desaturase Eicosanoids (AA)Arachidonic Acid (20:4n-6) (EPA) Eicosapentaenoic Acid (20:5n-3) Elongase 24:5n-3 Eicosanoids Leukotriene 5-series Prostaglandins E3 Thromboxanes A3 ∆-6 Desaturase Eicosanoids Leukotriene 4-series Prostaglandins E2 Thromboxanes A2 24:6n-3 β-Oxidation (DHA) Docosahexaenoic Acid (22:6n-3)

35. Omega 3 EFA’s: mechanism • Neuronal membrane structure and function • Brain development • Second messenger inside cells

36. 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)

37. 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

38. 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!

39. 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

40. 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

41. 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

43. 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

44. Bottom line on Amino acids andB vitamins • Healthy diet rich in green vegetables and nutritious protein sources • Consider B-complex supplement

45. 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)

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

47. 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

48. Non-dairy sources of calcium • Soy beans, tofu • Calcium fortified OJ • Green leafy vegetables (broccoli)

49. 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

50. Lifestyle: Stress management • Stress is common • Stress commonly triggers mood problems • Managing stress: exercise, sleep, nutrition, mind/emotion/body/spirit • Meditation • Biofeedback