Anorexia is a life threatening illness that is currently poorly understood.

1. Anorexia is a life threatening illness that is currently poorly understood. Treatment is complex, expensive, long-term and frequently difficult to access. The effects of starvation and dehydration is largely ignored by the Medical and Psychiatric professionals. Countertransferance issues with eating disorder patients frequently impair quality of treatment.

2. Am J Psychiatry (2005) • 20 Sessions CBT, IP or Supportive therapy for AN. • Supportive therapy was superior to interpersonal psychotherapy and cognitive behavioral therapy!

3. Prognosis of Early Onset Eating Disorders • Poor prognosis if develop AN before 11 (Bryant-Waugh, et.al., 1988; Ratnasuriya, et.al., 1992) • Early onset – good prognosis (Treasure & Schmidt, 2002)

4. A Life Threatening Illness • Anorexia Nervosa has the highest mortality rate of any psychiatric disorder. The most common causes of death are complications of starvation and suicide. • The mortality rate at five years is 5%, increasing to 20% at 20 years F/U (APA 2000).

5. A Chronic Illness There is a significant risk of relapse for up to two years after weight restoration.

6. Genetics A majority of young woman diet at some point in time yet only a small fraction develop eating disorders. Why?

7. Misplaced Blame • Eating disorders have traditionally been viewed as psychiatric illnesses that are strongly influenced by social pressures towards thinness. • Recent research suggests a substantial influence of genetic factors on the development of an eating disorder. • Family Twin and molecular genetic studies support substantial genetic influences on eating disorders.

8. Family Studies 7 – 12x increase in the prevalence of Anorexia and Bulimia in relatives of eating disorder patients.

9. Twin Studies • 58 – 76% of the variance in the liability to AN and 54 – 83% of the variance in the liability to BN can be accounted for by genetic factors. • No genetic factors in weight preoccupation and eating pathology in 11 year old twins. • 52 – 57% variance in eating pathology in 17 year old twins.

10. Twin Studies • 11 year old twins were divided into a pre- and post-pubertal group. • Genetic factors accounted for zero percent of variance in weight preoccupation and overall eating pathology in pre-pubertal twins. • Genetic factors accounted for 26 – 35% of the variance in post-pubertal twins.

11. Twin Studies Increased heritability in post-pubertal twins relative to pre-pubertal twins provides strong evidence of potential pubertal activation of the heritability of the eating pathology.

12. The Genetics of Eating Disorders • Activation of the heritability of eating pathology may be mediated by ovarian hormones. • Cultural attitudes toward thinness have relevance to the psycho-pathology of eating disorders, but they are unlikely to be sufficient to account for the pathogenesis of these disorders.

13. Genetics - AN Candidate genes for AN has been found on chromosome 1 in an area that controls Serotonin and opiate receptor genes.

14. Genetics - BN A susceptibility gene for Bulimia Nervosa was recently found on chromosome 10.

15. The Cycle of Risk • A mother with a history of anorexia (recovered) continues to have a consistent pattern of under-nutrition during pregnancy. • What is this doing to the fetus?

16. Malnourished Minds • An increasing percentage of a “healthy” random sampling of adolescents and adults are found to be deficient in essential nutrients. • Standards of health inadequate?

17. No Fat Diets! • No source of Fat Soluble Vitamins. • No source of Essential Fatty Acids. • But ... at least 25% of the brain’s white matter consists of phospholipids derived from essential fatty acids. • 60% dry weight of the brain is fat.

18. Fatty Acids • Function as building blocks of every cell in the body. • 20 specific Fatty Acids required by the human body to maintain normal functioning. • The body can make all but two: • Omega 3 – linolenic acid • Omega 6 – linoleic acid

19. Essential Fatty Acids are Involved in Neurotransmission • Synthesis • Degradation • Release • Re-uptake • Binding

20. Anorexia Nervosa • Psychotropic Drug Therapy Adjunctive • Primary Interventions • - Inpatient • - Partial Hospital • - Family Therapy • - Individual Therapy • - Nutritional Intervention

21. Anorexia Nervosa • 1960’s --Chlorpromazine/Insulin • 1980’s --TCAs--Clomipramine, Amitriptyline --Neuroleptics--Pimozide, Sulpiride --Other--Cyproheptadine

22. Anorexia Nervosa • More recently • SSRIS • Atypical Neuroleptics

23. Anorexia Nervosa FindingsEvidence Low Weight SSRIs don’t work + + Atypicals in resistant + Weight SSRIs help prevent + + Recovered relapse 3

24. SSRIs in Low Weight AN • Low tryptophan levels (↓L-Tryp./LNAA) • Inadequate serotonin response? • Tryptophan supplementation not helpful

25. Antipsychotics • 1960’s - CPZ tried for everything - CPZ + Insulin + Bed rest • 1970’s/1980’s - Haldol - Not well to tolerated/little effect • 1990’s/2000’s - Atypical, Zyprexa, Risperdol

26. Atypical Antipsychotics • 5HT2A:D2 Blocking Profile • ↓EPSE

27. Atypical Antipsychotics NDrugDosage 1996 Fosman 1 RIS 1 Mg 1999 Hansen 1 OLA 5 mg 2000Jansen & Mejlhede 3 OLA 5 mg 2000 LaVia et al. 2 OLA 5 mg 2000 Newman-Toker 2 RIS 1.5 mg 2001 Mehler et al. 5 OLA 5-12.5 mg 2001 Ruggiero et al. 35 Variable Variable 2001 Gaskill et al. 23 OLA 1.25-15mg* 2002 Carver et al. 15 RIS 0.5-1.5 mg* 2002 Powers et al. 18 OLA 10 Mg 2003 Boachie et al. 4 OLA 2.5 mg 2004 Powers et al. 13 QUE Variable * Negative (Non-randomized or retrospective)

28. Anorexia Antidepressants • Controlled studies have failed to demonstrate any advantage to adding an SSRI to nutritional and psychosocial interventions in the Tx of hospitalized malnourished patients with AN

29. Anorexia THE LITERATURE……… • Medications are used after weight restoration and normalized eating behaviors to maintain weight and treat Co-Morbid Psych illness

30. Anorexia Clinical Experience • Atypical Neuroleptics • Anticonvulsant/Antidepressant combinations • Zinc and targeted Nutritional Repletion

31. Anorexia Nervosa Low WeightIf resistant } Add Olanzepine if very obsessional } Add Olanzepine If not making } Add Progress Olanzepine Wt. RestoredUse SSRI (usually Fluoxetine) at least one year

32. Other Agents Negative - Lithium - THC - Zinc - Cyproheptodine

33. Cyproheptadine • Double blind placebo controlled trial 4-8Mg TID was associated with weight gain and ↓ depressive symptoms in anorexia nervosa patients • Up to 28m/day • Does not ↓ BP or ↑ HR

34. Zinc • Similarities between symptoms of Zinc deficiency and Anorexia Nervosa: - Weight loss - Alterations in taste and appetite - Depression - Amenorrhea

35. Zinc • Lower levels of zinc excretion in adolescent patients with AN compared to controls • Serum levels may be normal in cases of mild but chronic zinc deficiency

36. Zinc • Melatonin production is regulated by Zinc • Melatonin has direct effects on dopominergic noradrenergic and serotonergic functions

37. Zinc • Inadequate Dietary Intake? - Zinc Intake – 12 Healthy Control, 33 EDPfs - Controls – 11.95 mgs/day - Bulimics – 8.93 mgs/day - Anorexia's – 6.46 mgs/day

38. Zinc Birmingham et al (1994) • DBPC 100mg/day Zinc vs. Placebo • 35 female inpatients • Baseline Zinc levels normal • The rate of increase in BMI was significantly faster in patients receiving daily zinc than those receiving placebo

39. Zinc Lack et al (1993) • DBPC 50mg/day • 12 wk crossover design with 26 hospitalization children • No significant difference was seen in rate of weight gain between zinc supplements and placebo groups

40. Zinc • Zinc deficiency may act as a sustaining factor for abnormal eating behavior in certain eating disorder patients • Zinc Supplements are safe, inexpensive and may benefit many malnourished AN

41. Pediatric Psychopharmocolgy • AN and BN typically have their onset during adolencence and early childhood, the overwhelming majority of medication trials have been conducted among patients 18 years of age and older • Substantial Clinical and biological heterogereiting among patients with anorexia may obscure benefits of medication in some patients

42. Pediatric Psychopharm • Double blind studies in progress for (age 12-21) Zyprexa and Risperdal • Atypical Neuroleptics have no pediatric indications • There is a higher risk of side effects (TD & EPS) in children treated with neuroleptis

43. Pediatric Psychopharm • There are no medications approved to treat eating disorders in children or adolescents

44. Pediatric Psychopharm • Only Fluoxetine is approved for the treatment of depression in children • Recent SSRI controversy has led to more conservative prescribing • Fluvoxomine and Sertroline approved for pediatric OCD

45. Bulimia Diagnosis – Eating binges followed by purging behaviors such as self induced vomiting or laxative abuse • 1 - 3% of adolescent girls and young women • 5 – 10 times more common in women

46. Bulimia Nervosa DrugFindingsEvidence Fluoxetine ↓BE/P + + + SSRI’s Fluoxetine Prevent Relapse + Fluvoxamine No evidence o ________________________________________________________________________________ Imipramine ↓BE/P + + TCAs Desipramine ↓BE/P + + Amitriptyline +/- ↓BE/P + ________________________________________________________________________________ Pheneizine ↓BE/P + + MAO’s Meclobemide ↓BE/P + + Isocarboxazide ↓BE/P + ________________________________________________________________________________ Bupropion ↓BE/P Contraindiction OTHER Trazadone ↓BE/P + Mianserin No evidence O

47. Bulimia Nervosa Start 20 mg 60 mg Fluoxetine Start 60 mg Citalopram Start 20 mg 60 mg ConsiderConsiderConsider TCAAs Topiramate Naltrexone Effexor Ondansetron Strattera

48. Bulimia Nervosa • Psychotropic drug therapy well established • Primary intervention - CBT - Begin Drug Therapy if lack of early response - Begin Drug Therapy if depressed

49. A Chronic Persistent Illness • Approximately 50% of bulimic patients including those who have been treated continue to show eating disorder features on long term follow up.

50. Psychiatric Comorbidity • Most bulimic patients report a history of other psychiatric disorders. • Psychiatric comorbidities may occur before, during or after Bulimia Nervosa. • Unlikely a cause or consequence of Bulimia.