Pharmacotherapy
Primary or
initial treatment with pharmacotherapy is not indicated for AN. However, for
acutely ill patients that do not gain weight with psychotherapy and nutritional
rehabilitation, adjunctive pharmacotherapy is indicated.(1,2) Medication is
also indicated when patients have significant comorbid psychopathology (e.g. disabling anxiety or depressive
symptoms).(2) Many patients refuse medication. In addition, there are few double blind, placebo-controlled trials on pharmacotherapy
and most are limited by medical complications, small sample sizes, high dropout
rates and hesitant attitudes toward treatment.(3)
Antidepressants
According to a Cochrane systemic review by Claudino et al., there is a lack of quality evidence for the use of antidepressants in AN 22. Many of the trials have major methodological limitations like large confidence intervals and small trial size.(4) Unless another clinical indication exists antidepressants are not recommended in the treatment of AN.(3)
If an individual weighs less than 85% of normal body weight for their age, data propose that antidepressants are ineffective. Therefore, antidepressants should only be started if anxiety, obsessions, or depression persist after normal body weight is achieved.(3) In a small randomized study by Attia et al., no significant differences in psychological state or measures of eating behavior or body weight existed between the fluoxetine and the placebo group.(5) In this study, treatment was given before weight restoration.(5) In addition, there is debate on the effectiveness of antidepressants after weight is restored. Moreover, to help prevent relapse and maintain weight, psychotherapy along with antidepressants have been used; however there is limited data supporting this.(3)
Selective serotonin reuptake inhibitor (SSRI) antidepressants are preferred by most clinicians since they are safer than monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), in terms of cardiovascular events, and they are better tolerated. If TCAs or MAOIs are chosen low starting doses should be used along with slow titration because AN patients are sensitive to cardiovascular and anticholinergic effects.(3)
The most extensively studied SSRI in AN is fluoxetine. Study results on the effectiveness of fluoxetine in AN are mixed.(6) In a small study with a high dropout rate by Walsh et al., there was no difference in treatment retention or relapse prevention between fluoxetine and placebo when treatments were given after weight restoration.(7) On the contrary, a small randomzied study with a high dropout by Kaye et al. showed that fluoxetine may be correlated with reduction in symptoms and increased body weight over 1 year.(8) The treatments were given after weight was gained.(8) Furthermore, in a small-randomized trial with a high dropout rate by Fassino et al., citalopram seemed to decrease obsessive-compulsive symptoms, depression scores, trait anger and impulsiveness.(9) There is a lack of evidence for the use of TCAs for weight gain in AN.(6)
Antipsychotics
There is insufficient evidence for the use of atypical antipsychotics in AN patients.(6,10) Evidence comes from small trials or case reports using olanzapine 2.5 to 10 mg daily or risperidone 0.5 to 1.5 mg daily.(3) In a small-randomized study by Bissada et al., olanzapine accelerated weight gain and improved obsessive symptoms.(11) In a small randomized study by Mondraty et al., olanzapine reduced the degree of anorexic ruminations.(12) On the contrary in a small study by Brambilla et al., olanzapine was no different than placebo at improving BMI in individuals with AN on CBT.(13) Most studies lasted 3 months or less, therefore optimal duration of treatment is unknown.(3) However, due to the extrapyramidal adverse effects of these medications they should only be used until weight is restored (maximum BMI 17 kg/m2).(13)
Prokinetic Agents
Metoclopramide and domperidone can help reduce abdominal pain, bloating and early satiety. These are common symptoms in AN particularly during early refeeding.(3,14) Domperidone has a lower frequency of extrapyramidal side effects and is therefore preferred. However, if an antinauseant effect is needed thenmetoclopramide is preferred. These medications have the potential to cause QT prolongation and this should be taken into consideration before initiating therapy.(14)
Benzodiazepines
When eating is limited by severe anxiety, low-dose, short-acting benzodiazepines (0.5 mg lorazepam or 0.25 mg alprazolam) are useful when given before meals.(3)
Cyproheptadine
In 3 randomized trials, cyproheptadine was associated with a very small benefit at best for achieving target body weight during hospitalization.(6) Cyproheptide can be used as a hypnotic.(14)
Zinc Gluconate
In a small-randomized trial with a large dropout by Birmingham et al., zinc supplementation was associated with increased rate of weight gain.(15) In another randomized study by Katz et al., zinc supplementation reduced anxiety and depression.(16) Nausea is a side effect of zinc in about 2% of patients, but if it is taken with food this adverse effect can be reduced.(14)
Thiamine
At the start of feeding, thiamine (100 mg/day) should be given for 5 days to prevent Wernicke-Korsakoff syndrome from occurring.(14)
Investigational Approach
For intractable anorexia nervosa deep brain stimulation (DBS) is a potentially safe and beneficial investigational procedure.(1) In a prospective observational study by Lipsman et al., improvement of anxiety and mood symptoms and weight gain occurred in some patients.(17) Side effects include intraoperative panic attack, seizure, air embolus, and pain.(1)
"Brain surgery gives 'new life' to anorexia patient " (18)
Antidepressants
According to a Cochrane systemic review by Claudino et al., there is a lack of quality evidence for the use of antidepressants in AN 22. Many of the trials have major methodological limitations like large confidence intervals and small trial size.(4) Unless another clinical indication exists antidepressants are not recommended in the treatment of AN.(3)
If an individual weighs less than 85% of normal body weight for their age, data propose that antidepressants are ineffective. Therefore, antidepressants should only be started if anxiety, obsessions, or depression persist after normal body weight is achieved.(3) In a small randomized study by Attia et al., no significant differences in psychological state or measures of eating behavior or body weight existed between the fluoxetine and the placebo group.(5) In this study, treatment was given before weight restoration.(5) In addition, there is debate on the effectiveness of antidepressants after weight is restored. Moreover, to help prevent relapse and maintain weight, psychotherapy along with antidepressants have been used; however there is limited data supporting this.(3)
Selective serotonin reuptake inhibitor (SSRI) antidepressants are preferred by most clinicians since they are safer than monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), in terms of cardiovascular events, and they are better tolerated. If TCAs or MAOIs are chosen low starting doses should be used along with slow titration because AN patients are sensitive to cardiovascular and anticholinergic effects.(3)
The most extensively studied SSRI in AN is fluoxetine. Study results on the effectiveness of fluoxetine in AN are mixed.(6) In a small study with a high dropout rate by Walsh et al., there was no difference in treatment retention or relapse prevention between fluoxetine and placebo when treatments were given after weight restoration.(7) On the contrary, a small randomzied study with a high dropout by Kaye et al. showed that fluoxetine may be correlated with reduction in symptoms and increased body weight over 1 year.(8) The treatments were given after weight was gained.(8) Furthermore, in a small-randomized trial with a high dropout rate by Fassino et al., citalopram seemed to decrease obsessive-compulsive symptoms, depression scores, trait anger and impulsiveness.(9) There is a lack of evidence for the use of TCAs for weight gain in AN.(6)
Antipsychotics
There is insufficient evidence for the use of atypical antipsychotics in AN patients.(6,10) Evidence comes from small trials or case reports using olanzapine 2.5 to 10 mg daily or risperidone 0.5 to 1.5 mg daily.(3) In a small-randomized study by Bissada et al., olanzapine accelerated weight gain and improved obsessive symptoms.(11) In a small randomized study by Mondraty et al., olanzapine reduced the degree of anorexic ruminations.(12) On the contrary in a small study by Brambilla et al., olanzapine was no different than placebo at improving BMI in individuals with AN on CBT.(13) Most studies lasted 3 months or less, therefore optimal duration of treatment is unknown.(3) However, due to the extrapyramidal adverse effects of these medications they should only be used until weight is restored (maximum BMI 17 kg/m2).(13)
Prokinetic Agents
Metoclopramide and domperidone can help reduce abdominal pain, bloating and early satiety. These are common symptoms in AN particularly during early refeeding.(3,14) Domperidone has a lower frequency of extrapyramidal side effects and is therefore preferred. However, if an antinauseant effect is needed thenmetoclopramide is preferred. These medications have the potential to cause QT prolongation and this should be taken into consideration before initiating therapy.(14)
Benzodiazepines
When eating is limited by severe anxiety, low-dose, short-acting benzodiazepines (0.5 mg lorazepam or 0.25 mg alprazolam) are useful when given before meals.(3)
Cyproheptadine
In 3 randomized trials, cyproheptadine was associated with a very small benefit at best for achieving target body weight during hospitalization.(6) Cyproheptide can be used as a hypnotic.(14)
Zinc Gluconate
In a small-randomized trial with a large dropout by Birmingham et al., zinc supplementation was associated with increased rate of weight gain.(15) In another randomized study by Katz et al., zinc supplementation reduced anxiety and depression.(16) Nausea is a side effect of zinc in about 2% of patients, but if it is taken with food this adverse effect can be reduced.(14)
Thiamine
At the start of feeding, thiamine (100 mg/day) should be given for 5 days to prevent Wernicke-Korsakoff syndrome from occurring.(14)
Investigational Approach
For intractable anorexia nervosa deep brain stimulation (DBS) is a potentially safe and beneficial investigational procedure.(1) In a prospective observational study by Lipsman et al., improvement of anxiety and mood symptoms and weight gain occurred in some patients.(17) Side effects include intraoperative panic attack, seizure, air embolus, and pain.(1)
"Brain surgery gives 'new life' to anorexia patient " (18)
References
1. Forman SF. Eating disorders: Overview of treatment. UpToDate. http://www.uptodate.com/contents/eating-disorders-overview-of-treatment. Updated March 25, 2013. Accessed June 1, 2013.
2. Treatment of patients with eating disorders,third edition. American Psychiatric Association. American Psychiatric Association. Am J Psychiatry. 2006;163(7 Suppl):4-54.
3. Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC. Chapter 64. Multiple Sclerosis. In: Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7984977. Accessed June 1, 2013.
4. Claudino AM, Hay P, Lima MS, et al. Antidepressants for anorexia nervosa. Cochrane Database Syst Rev. 2006;(1):CD004365.
5. Attia E, Haiman C, Walsh BT, Flater SR: Does fluoxetine augment the inpatient treatment of anorexia nervosa? Am J Psychiatry 1998; 155:548–551 [A]
6. Anorexia Nervosa. DynaMed. http://web.ebscohost.com/dynamed/detail?vid=3&sid=b9c41bae-db1d-4f87-bca4-5bfac549946f%40sessionmgr112&hid=123&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#db=dme&AN=114614. Updated February 20, 2013. Accessed June 1, 2013.
7. Walsh BT, Kaplan AS, Attia E, et al. Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial. JAMA. 2006;295(22):2605-12.
8. Kaye WH, Nagata T, Weltzin TE, Hsu LK, Sokol MS, McConaha C, Plotnicov KH, Weise J, Deep D: Double-blind placebo-controlled administration of fluoxetine in restricting- and estricting-purging-type anorexia nervosa. Biol Psychiatry 2001; 49:644–652 [A]
9. Fassino S, Leombruni P, Daga G, et al. Efficacy of citalopram in anorexia nervosa: a pilot study. Eur Neuropsychopharmacol. 2002 Oct;12(5):453-9.
10. Bosanac P, Norman T, Burrows G, et al. Serotonergic and dopaminergic systems in anorexia nervosa: a role for atypical antipsychotics? Aust N Z J Psychiatry. 2005 Mar;39(3):146-53.
11. Bissada H, Tasca GA, Barber AM, et al. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008;165(10):1281-8.
12. Mondraty N, Birmingham CL, Touyz S, et al..Randomized controlled trial of olanzapine in the treatment of cognitions in anorexia nervosa. Australas Psychiatry. 2005 Mar;13(1):72-5.
13. Brambilla F, Monteleone P, Maj M. Olanzapine-induced weight gain in anorexia nervosa: involvement of leptin and ghrelin secretion? Psychoneuroendocrinology. 2007;32(4):402-6.
14. Psychiatric Disorders: Eating Disorders. e-Therapeutics. https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0108. Updated January 2012. Accessed June 1, 2013.
15. Birmingham CL, Goldner EM, Bakan R. Controlled trial of zinc supplementation in anorexia nervosa. Int J Eat Disord. 1994 Apr;15(3):251-5.
16. Katz RL, Keen CL, Litt IF, et al. Zinc deficiency in anorexia nervosa. J Adolesc Health Care. 1987;8(5):400-6.
17. Lipsman N, Woodside DB, Giacobbe P, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013; 381:1361.
18. Brain surgery gives 'new life' to anorexia patient. Youtube. http://www.youtube.com/watch?v=VrOW1SjewRk. Accessed June 1, 2013.
1. Forman SF. Eating disorders: Overview of treatment. UpToDate. http://www.uptodate.com/contents/eating-disorders-overview-of-treatment. Updated March 25, 2013. Accessed June 1, 2013.
2. Treatment of patients with eating disorders,third edition. American Psychiatric Association. American Psychiatric Association. Am J Psychiatry. 2006;163(7 Suppl):4-54.
3. Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC. Chapter 64. Multiple Sclerosis. In: Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7984977. Accessed June 1, 2013.
4. Claudino AM, Hay P, Lima MS, et al. Antidepressants for anorexia nervosa. Cochrane Database Syst Rev. 2006;(1):CD004365.
5. Attia E, Haiman C, Walsh BT, Flater SR: Does fluoxetine augment the inpatient treatment of anorexia nervosa? Am J Psychiatry 1998; 155:548–551 [A]
6. Anorexia Nervosa. DynaMed. http://web.ebscohost.com/dynamed/detail?vid=3&sid=b9c41bae-db1d-4f87-bca4-5bfac549946f%40sessionmgr112&hid=123&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#db=dme&AN=114614. Updated February 20, 2013. Accessed June 1, 2013.
7. Walsh BT, Kaplan AS, Attia E, et al. Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial. JAMA. 2006;295(22):2605-12.
8. Kaye WH, Nagata T, Weltzin TE, Hsu LK, Sokol MS, McConaha C, Plotnicov KH, Weise J, Deep D: Double-blind placebo-controlled administration of fluoxetine in restricting- and estricting-purging-type anorexia nervosa. Biol Psychiatry 2001; 49:644–652 [A]
9. Fassino S, Leombruni P, Daga G, et al. Efficacy of citalopram in anorexia nervosa: a pilot study. Eur Neuropsychopharmacol. 2002 Oct;12(5):453-9.
10. Bosanac P, Norman T, Burrows G, et al. Serotonergic and dopaminergic systems in anorexia nervosa: a role for atypical antipsychotics? Aust N Z J Psychiatry. 2005 Mar;39(3):146-53.
11. Bissada H, Tasca GA, Barber AM, et al. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2008;165(10):1281-8.
12. Mondraty N, Birmingham CL, Touyz S, et al..Randomized controlled trial of olanzapine in the treatment of cognitions in anorexia nervosa. Australas Psychiatry. 2005 Mar;13(1):72-5.
13. Brambilla F, Monteleone P, Maj M. Olanzapine-induced weight gain in anorexia nervosa: involvement of leptin and ghrelin secretion? Psychoneuroendocrinology. 2007;32(4):402-6.
14. Psychiatric Disorders: Eating Disorders. e-Therapeutics. https://www.e-therapeutics.ca/tc.showChapter.action?documentId=c0108. Updated January 2012. Accessed June 1, 2013.
15. Birmingham CL, Goldner EM, Bakan R. Controlled trial of zinc supplementation in anorexia nervosa. Int J Eat Disord. 1994 Apr;15(3):251-5.
16. Katz RL, Keen CL, Litt IF, et al. Zinc deficiency in anorexia nervosa. J Adolesc Health Care. 1987;8(5):400-6.
17. Lipsman N, Woodside DB, Giacobbe P, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013; 381:1361.
18. Brain surgery gives 'new life' to anorexia patient. Youtube. http://www.youtube.com/watch?v=VrOW1SjewRk. Accessed June 1, 2013.