Anorexia Nervosa

The Eating Disorders are broken down into two categories: Anorexia Nervosa and Bulimia. Anorexia is characterized by a refusal to maintain a minimal adequate normal weight. Bulimia has repeated episodes of binge eating followed by self-induced vomiting, misuse of laxatives, diuretics, or other medications which are used to offset the over-eating. Simple obesity is considered a medical, not a psychiatric disorder. In fact, medical causes play important roles in both anorexia nervosa and bulimia.

Anorexia Nervosa

Anorexia nervosa (AN) has an individual who refuses to maintain a minimally adequate normal weight, is intensely afraid of gaining weight, and has a disturbance in the perception of the shape or size of his or her body. Females usually stop menstruating because their weight becomes so low. While there is no specific weight cutoff, individuals below 85% of their ideal weight or who have a BMI under 17.5 kg/m2 fall in this range. Individuals suffering from this disorder usually restrict their normal food intake to remain underweight but may also induce vomiting, use laxatives or diuretics, and/or engaging in excessive exercising. They have an intense fear of gaining weight and often think of themselves as fat. Their fear often increases even as they get thinner and thinner. Some may realize that they are thin, but think particular parts of their bodies are too fat.

Anorexics become obsessed with their body shape and weight, often repeatedly measuring body parts or persistently using a mirror to check their shape. They consider weight loss a tremendous accomplishment and weight gain a terrible loss of self-control. Anorexics often suffer from depression, social withdrawal, irritability, insomnia, and a diminished interest in sex. Most are preoccupied with food. They may collect recipes or hoard food. They may be concerned about eating in public, feel ineffective, engaging in inflexible thinking, and be over-restrained emotionally.

The mean age of onset is 17 and it is most common in teenage and young adult females and homosexual men. About one in 100-200 teenage women mean the full criterion for diagnosis and still more suffer many of the features but are not severe enough to receive the diagnosis. Although some patients do die from starvation or medical complications, recent large studies have not been able to document an increased death rate.

AN Lower Suicide Risk: Study of death records of 5 million women found those with AN died of suicide only 1.4% of time vs. 4.1% for matched controls. This is a finding the opposite of anecdotal reports by various clinicians. Coren, U Brit Col, Am J Publ Health ’98:88:1206-7

No Decreased Survival: Mayo study following 208 eating disordered patients found only one death due to disorder with follow-up up to 63 years of Minnesota patients. 93% survived for 30 years after diagnosis of anorexia nervosa, identical to controls. Deaths = 1 AN, 2 suicides, 6 alcoholism, 3 cardiovascular (10 expected!). Lucas, 3/13/03, Mayo Clinic Proceedings

CART Hormone Increased: Cocaine- and amphetamine-regulated transcript (CART) is increased in AN and decreases as patients gain weight. British Endocrine Societies' annual meeting, Dr. Sarah A. Stanley, Imperial College of Science, Technology and Medicine in London. CART is known to affect appetite in animal studies. Researchers also measured alpha-melanocyte-stimulating hormone and glucagon-like peptide in 13 women with anorexia nervosa being treated at the Maudsley. CART levels were raised by about 50% compared to normal controls. The level of the two other hormones did not differ. 4/4/03

Autoantibodies Common in Anorexia Nervosa, Bulimia: 57 pt and 13 controls tested. 75% pts positive for antibodies bound to melanotropes or corticotropes in rat brain pituitary preparations vs. 16% of controls. 20% of the positives had specific antibodies to hypothalamic alpha-MSH producing neurons. alpha-MSH is the first 13 peptides of ACTH. Serguei Fetissov, Karolinska Inst. Proceedings Natl Acad Sci 12/9/02.

Meat: Half Anorexics Become Red Meat Avoiders: A retrospective study was carried out of 116 consecutive patients with anorexia nervosa to ascertain the extent and nature of vegetarianism in this population. Sixty-three (54.3%) patients were found to be avoiding red meat. In only four (6.3%) of these did meat avoidance predate the onset of their anorexia nervosa. Of the remaining 59 patients (best termed pseudovegetarians), 25 (42.4%) patients continued to avoid red meat by the end of treatment. Vegetarianism in anorexia nervosa? A review of 116 consecutive cases. O'Connor MA, Touyz SW, Dunn SM, Beumont PJ. Med J Aust 1987 Dec 7-21;147(11-12):540-2

Medical Abnormalities Common in Anorexia: In a cross-sectional, community-based study of 214 women with anorexia nervosa, the prevalences of medical findings were as follows: anemia, 39%; leukocytopenia, 34%; hyponatremia, 20%; hypokalemia, 20%; bradycardia, 41%; hypotension, 16%; hypothermia, 22%; elevation of alanine aminotransferase concentration, 12%; osteopenia, 52%; osteoporosis, 35%; and primary amenorrhea, 15%. Moreover, 30% of the women reported histories of bone fractures. Except for leukocytopenia (P = .01), bone loss (P = .04), and bradycardia (P = .01), the probability of specific medical findings could not be predicted by the degree of undernutrition. Medical findings in outpatients with anorexia nervosa. Miller KK, et al. MGH-Harvard. . Arch Intern Med. 2005 Mar 14;165(5):561-6.

Melatonin Cycle Flattened; Same in Obesity: Researchers measured the circadian rhythms of plasma melatonin, serum cortisol, growth hormone (GH) and prolactin (PRL) in 26 patients with anorexia nervosa (AN), 27 with primary obesity (OB) and 7 with bulimia nervosa (BN). They found daytime persistence of melatonin in AN and OB, and similar cortisol changes in AN and BN. Circadian neuroendocrine functions in disorders of eating behavior. Ferrari E, Magri F, et al. University of Pavia, Italy. Eat Weight Disord. 1997 Dec;2(4):196-202

Mortality High in Anorexia Study: In a cross-sectional study of 954 patients, including all 326 diagnosed with AN from 1981-2000, the standard mortality ratio was 10.5 for AN. This studies reports a high mortality rate within the AN population. The mortality rate from anorexia nervosa. Birmingham CL, et al. University of British Columbia, Vancouver, British Columbia, Canada. . Int J Eat Disord. 2005 Sep;38(2):143-6.

One-Quarter Fall Short of Full Diagnosis: 588 consecutive admissions to an in-patient program. 297 females had some form of AN with 77.4% (230 of 297) meeting full criteria; 22.6% (67 of 297) with core psychopathology and self-starvation were classified as eating disorders not otherwise specified because of some menstrual function or final weight above 85%. The groups showed few statistically significant differences on demographics, illness history, and treatment response, psychopathology, or bone density. Univ of Iowa. A critical examination of the amenorrhea and weight criteria for diagnosing anorexia nervosa. Watson TL, Andersen AE. Acta Psychiatr Scand. 2003 Sep;108(3):175-82

Osteoporosis More Common in Depressed Anorexics: Forty-five Polish anorexic girls aged 13-23 yr, matched by age, the 14 with comorbid depression had lower BMD than those with AN alone (LS Z-scores, -2.6 vs. -1.7; P = 0.02). Quantitative assessment of depression correlated independently with total body BMD (r = -0.4; P < 0.05) and LS BMD (r = -0.6; P < 0.001). Depression in anorexia nervosa: a risk factor for osteoporosis. Konstantynowicz J, et al. University Children's Hospital, Bialystok, Poland. . J Clin Endocrinol Metab. 2005 Sep;90(9):5382-5.

Peptide YY May Play Role in Anorexia: PYY is an intestinally derived anorexigen that acts via the Y2 receptor. Y2 receptor deletion in rodents increases bone formation. Known regulators of bone turnover such as growth hormone (GH), cortisol and estrogen explain only a fraction of the variability in bone turnover marker levels. In 23 AN girls and 21 healthy adolescents 12-18 yr old, AN girls had much higher PYY levels compared with controls (17.8 vs. 4.8 pg/ml, P < 0.0001). Predictors of log PYY were nutritional markers including BMI (r = -0.62, P < 0.0001), fat mass (r = -0.55, P = 0.0003) and REE (r -0.51, P = 0.0006), and hormones including GH (r = 0.38, P = 0.004) and T3 (r = -0.59, P = 0.0001). BMI, fat mass, REE, GH and T3 explained 68% of the variability of log PYY. Log PYY predicted % calories from fat (r = -0.56, P = 0.0002), and independently predicted osteocalcin (r = -0.45, P = 0.003), bone specific alkaline phosphatase (r = -0.46, P = 0.003), N-telopeptide/creatinine (r = -0.55, P = 0.0003) and deoxypyridinoline/creatinine (r = -0.52, P = 0.001) on regression modeling. Elevated PYY may contribute to reduced intake and decreased bone turnover in AN. Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa. Misra M, et al. MGH-Harvard. J Clin Endocrinol Metab. 2005 Nov 8

Thiamine Deficiency Common: Deficiency of thiamin (vitamin B1) causes a range of neuropsychiatric symptoms that resemble those reported in patients with anorexia nervosa (AN). In a study of 37 anorexic patients vs. 50 blood donors, 38% of patients had thiamine deficiency and 19% met the most stringent criterion for deficiency. Deficiency was not related to duration of eating restraint, frequency of vomiting, or alcohol consumption. Prevalence of thiamin deficiency in anorexia nervosa. Winston AP, et al. University of Leicester, UK. . Int J Eat Disord. 2000 Dec;28(4):451-4.

Zinc and Folic Acid Low Even After Refeeding: Anorexics were still low on zinc and folic acid after short-term refeeding. Int J Eat Disord. 2004 Mar;35(2):169-78. Zinc deficiency in animals causes impaired growth and anorexia. Leptin levels in rats increased during zinc depletion. J Med Food. 2003 Winter;6(4):281-9; NPY is released from terminals in the paraventricular nucleus of the hypothalamus of food-restricted animals, this release is significantly impaired in zinc-deficient animals. Zinc deficiency may therefore cause anorexia by inhibiting the release of NPY that is required for receptor. Nutr Rev. 2003 Jul;61(7):247-9

Zinc Low in Anorexics and Bulimics: A Univ. of Kentucky study of hospitalized patients and controls with hospitalized patients started on zinc 75 mg/day found that both bulimics and especially anorexics had low zinc levels (376 vs. 258 vs. 196) and low intakes. Zinc status before and after zinc supplementation of eating disorder patients. McClain CJ, Stuart MA, Vivian B, McClain M, Talwalker R, Snelling L, Humphries L. J Am Coll Nutr. 1992 Dec;11(6):694-700; Some small studies have found no deficiency. Ugeskr Laeger. 1991 Mar 4;153(10):721-3; Eur J Clin Nutr. 1988 Nov;42(11):929-37

Zinc Low in Anorexics and Bulimics: A Univ. of Kentucky study of 62 bulimics and 24 anorexics found 40% of bulimics and 54% of anorexics had biochemical evidence of zinc deficiency. The authors suggest that for a variety of reasons, such as lower dietary intake of zinc, impaired zinc absorption, vomiting, diarrhea, and binging on low-zinc foods. J Clin Psychiatry. 1989 Dec;50(12):456-9

Treatment

Amisulpride did better than Fluoxetine, Clomipramine in One Small Study: Small single blind 36 pt. More wt gain with amisulpride and other factors were equal. A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics. Ruggiero GM, Laini V, Mauri MC, Ferrari VM, Clemente A, Lugo F, Mantero M, Redaelli G, Zappulli D, Cavagnini F. Prog Neuropsychopharmacol Biol Psychiatry 2001 Jul;25(5):1049-59

Fluoxetine Helps: DB PC 35 women hospitalized for AN. 63% fluox 10-60/d stayed on meds for year vs 16% placebo. Only those on fluox had incrases in weights and mood and eating disorder improvement. Bio Psyc 01;49:644. Little, Kay, U Pitt.

Fluoxetine No Benefit: 2 yr matched study prospectively 33 consecutively admitted patients put on fluoxetine 20-40/d. No patient discontinued therapy or was lost to f/u. Family and dietary counseling. Both groups improved with 70% at target wt at 2 yr and only 11% rehospitalized. Strober M, et al: Does adjunctive fluoxetine influence the post-hospital course of restrictor-type anorexia nervosa? a 24-month prospective, longitudinal followup and comparison with historical controls. Psychoph Bull 97;33:425-31, UCLA

Zinc Helps in Anorexia Nervosa: DB 100 mg/d in hospitalized patients (36) found patients on zinc had double the rate of weight gain in supplemented group! Controlled trial of zinc supplementation in anorexia nervosa. Brit. Columbia. Birmingham CL, Goldner EM, Bakan R. Int J Eat Disord 1994 Apr;15(3):251; Anorexia nervosa (AN) and zinc deficiency, found most frequently in young females, have a number of symptoms in common. These include weight loss, alterations in taste and appetite, depression, and amenorrhea. Approximately half of anorexia nervosa patients (ANs) are vegetarian (VANs), a practice that may increase their risk for zinc deficiency. This study compared the dietary intake of zinc and related nutrients in 9 outpatient VANs with that of 11 outpatient nonvegetarian patients with anorexia nervosa (NVANs). VANs reported significantly lower (p < .05) dietary intakes of zinc, fat, and protein, and a significantly higher (p < .05) intake of calories from carbohydrates than NVANs. There were no significant differences between the groups in dietary intake of calories, calcium, copper, iron, or magnesium. These findings indicate that zinc intake should be routinely assessed in VANs and that zinc supplementation of their diets may be indicated. Dietary zinc intake of vegetarian and nonvegetarian patients with anorexia nervosa. Bakan R, Birmingham CL, Aeberhardt L, Goldner EM. Int J Eat Disord 1994 Sep;16(2):205-9. Ed: Zinc supplementation does not appear popular as no other research using is for anorexia has been published in 10 years.

Zinc Low in Anorexics and Depression and Anxiety Lessened in DB: In a DB PC study of teen anorexics, zinc intake was found one-half that of controls and zinc excretion one-third that of controls. Those randomized to 50 mg/day zinc had a decrease in the level of depression and anxiety as assessed by the Zung Depression Scale (p less than 0.05) and the State-Trait Anxiety Inventory (p less than 0.05). Stanford. Zinc deficiency in anorexia nervosa. Katz RL, Keen CL, Litt IF, Hurley LS, Kellams-Harrison KM, Glader LJ. J Adolesc Health Care. 1987 Sep;8(5):400-6

Fluoxetine Helps Anorexia Nervosa: Ten of 16 (63%) subjects remained on fluoxetine for a year, whereas only three of 19 (16%) remained on the placebo for a year (p =.006). Those subjects remaining on fluoxetine for a year had reduced relapse as determined by a significant increase in weight and reduction in symptoms. U Pitt, Double-blind placebo-controlled administration of fluoxetine in restricting- and restricting-purging-type anorexia nervosa. Kaye WH, Nagata T, Weltzin TE, Hsu LK, Sokol MS, McConaha C, Plotnicov KH, Weise J, Deep D. Biol Psychiatry 2001 Apr 1;49(7):644-52

Heat Treatment Helps Anorexia Nervosa: Swedish approach using old technique of having anorexics rest in 104 degree rooms after eating found 75% returning to normal weight in average of 14 months, another 12% improving some, and only 7% relapsing in 7 year study. 7/02 Proceedings of the National Academy of Sciences. Anorexics usually have low body temperatures.

Heat Treatment with Sauna Mentioned: Progress shown by AN patients whose treatment consisted of different strategies of heat supply, which included a protocol of sauna sessions. First recommended by W. Gull, heat-treatment may be relevant to hyperactivity, a significant clinical characteristic in AN. This treatment was developed as an extrapolation from animal research model, where a simple manipulation of ambient temperature was found to impede and reverse excessive running in food-restricted rats. Spain. Do people with anorexia nervosa use sauna baths? A reconsideration of heat-treatment in anorexia nervosa. Gutierrez E, Vazquez R, Beumont PJ. Eat Behav. 2002 Summer;3(2):133-42

Heat Treatment with Warmer Jacket No Benefit: A random assignment 21-patient study by the Univ. of Brit. Columbia with hospitalized long-term anorexics failed to find any between group difference with 3 hours per day for 18 days with a warmer jacket. Randomized controlled trial of warming in anorexia nervosa. Birmingham CL, Gutierrez E, Jonat L, Beumont P. Int J Eat Disord. 2004 Mar;35(2):234-8

Bulimia Nervosa

To qualify for the diagnosis, the binge eater must binge an average of at least twice a week for three months and compensatory behaviors such as self-induced vomiting, laxatives, or diuretic use must be present. Between 80% and 90% use vomiting. Oddly, recent research shows that self-induced vomiting actually increases hunger. This may explain the vicious circle that many patients get into and why vomiting is not a successful method of losing weight. Many teenage girls pick up the habit in high school as a weight control technique only to fall into the cycle of bingeing and purging. Females make up over 90% of this disorder which appears of fairly recent origin. It was virtually unheard of 50 years ago.

Binge-Eating: Fluvoxamine Helped: 85 patients bingeing 3 or more times per week and weighing 85% or more over ideal weight were treated with fluvoxamine 50-300mg/d in a DB PC study. At 9 wk, fluvoxamine patients had at least a 75% decrease in binges in 45% of patients vs. 24% in placebo. CGI also better with 3# wt loss. Upjohn funding. McLean, Hudson, Amer J Psychiatry 98;155:1756

Binge-Eating: Citalopram Helps, Too: Another short 6 week SSRI DB PC trial of just 38 patients found citalopram 20-60mg/d quite helpful. Citalopram in the treatment of binge-eating disorder: a placebo-controlled trial. McElroy SL, Hudson JI, Malhotra S, Welge JA, Nelson EB, Keck PE Jr. Univ. Cincinnati. J Clin Psychiatry. 2003 Jul;64(7):807-13

Bulimia: Vomiting Causes Increased Hunger: Self induced vomiting leads to slower gastric emptying. Small amounts of early gastric emptying during a meal release cholecystokinin CCK which goes to the brain and causes feelings of satiety. Bulimics develop slower emptying. Abstaining from bulimia for three months causes gastric emptying rate to return to normal and return of normal feelings of satiety.

Bulimia: Fluoxetine Successful: DB PC fluoxetine 60mg/d 22 patients failing to respond to cognitive behavioral therapy or interpersonal therapy for bulimia. Therapy reportedly helps 50%. With fluoxetine, binges decreased 22 to 4 vs. increased 15 to 18. Fluoxetine purging decreased 30 to 6 v increased 15 to 38 on placebo. Walsh, Am J Psychiatry 00;157:1332, NIMH, Columbia U

Bulimia: Trazodone Helps in DB: 6-week, placebo-controlled, double-blind study of trazodone in 42 women with bulimia nervosa, trazodone was well tolerated and proved significantly superior to placebo in reducing the frequency of episodes of binge eating and vomiting. Nine- to 19-month follow-up of 36 study subjects revealed that 26 (72%) continued improved, with 18 (36%) in remission. Most remained on trazodone or another antidepressant at follow-up. Harvard: Treatment of bulimia nervosa with trazodone: short-term response and long-term follow-up. Hudson JI, Pope HG Jr, Keck PE Jr, McElroy SL. Clin Neuropharmacol 1989;12 Suppl 1:S38-46; Discussion S47-9

Bulimia: Many Anti-Depressants Work, Fluoxetine Fewer Drop-outs: 16 trials comparing antidepressants with placebo: 6 trials with TCAs (imipramine, desipramine and amitryptiline), 3 with SSRIs (fluoxetine), 4 with MAOIs (phenelzine, isocarboxazid and brofaromine) and 3 with other classes of drugs (mianserine, trazodone and bupropion). Similar results were obtained in terms of efficacy for these different groups of drugs. The pooled RR for remission of binge episodes was 0.88 (p<0,001) favoring drugs. The NNT for a mean treatment duration of 8 weeks, taking the non-remission rate in the placebo controls of 92% as a measure of the baseline risk was 9. The RR for clinical improvement, defined as a reduction of 50% or more in binge episodes was 0.63 and the NNT for a mean treatment duration of 9 weeks was 4, with a non-improvement rate of 67% in the placebo group. Patients treated with antidepressants were more likely to interrupt prematurely the treatment due to adverse events. Patients treated with TCAs dropped-out due to any cause more frequently that patients treated with placebo. The opposite was found for those treated with fluoxetine. Antidepressants versus placebo for people with bulimia nervosa. Bacaltchuk J, Hay P., U Sao Paolo, Cochrane Database Syst Rev 2001;(4):CD003391

Topiramate Helps in DB: An 8-week DB PC trial of 69 patients found a 48% decrease in binging and purging with topiramate started at 25 mg/d and gradually increased at 25 mg/d up to a maximum of 400 mg/d. The placebo group had an 11% decrease. U Utah, Brigham Young, and the producer. Treatment of Bulimia Nervosa With Topiramate in a Randomized, Double-Blind, Placebo-Controlled Trial, Part 1: Improvement in Binge and Purge Measures. Hoopes SP, Reimherr FW, Hedges DW, Rosenthal NR, Kamin M, Karim R, Capece JA, Karvois D. J Clin Psychiatry. 2003 Nov;64(11):1335-1341. Ed: Topiramate has a high rate of side-effects and is much more costly ($250/mo. for 400 mg/d) than fluoxetine, nortriptyline, trazodone, or a number of other well proven treatment. Topiramate does not seem more effective based on the percentages given, although no comparative trials are available.

Eating Disorders

APA 5/17/99: Yale psychiatrist. The number of admissions markedly increased from 1984-98 in one unit because managed care became very restricted. Researchers have been looking for serotonin polymorphisms. Studies have shown AN and bulimia nervosa (BN) run in families. Twin studies show variance accounted for significantly by genetics. Many studies have shown a dysregulation in serotonerigic system in AN and BN. ANR= anorextic restrictive type. Perfectionism preceeds AN. Perfectionism is higher in both AN and BN. AN more perfectionistic than BN but both higher than norms. 64% of ANRs had some obsessions or compulsions and 80% of Binge-Purge Anorexics did, too. Cognitive behavioral therapy did best for BN and interpersonal psychotherapy can help as can fluoxetine and desipramine. Those not responding to CBT have more depression and personality problems. Only 20% responded to fluoxetine or imipramine or to IPT. Fluoxetine helps binge-purgers more. At one year, fluoxetine patients had relapsed at 33% vs. 52% on placebo. Even with fluoxetine, patients continued to have considerable symptoms. Huge dropout rate in studies since AN patients resist treatment. Fluoxetine actually did better than CBT at 6 month in one study. AN is much more common in industrialized countries including Taiwan vs. Mainland China. Family treatment for minors is important according to a Maudsley studies.