Treatment Options for Anorexia Nervosa

US Pharm. 32(11):63-70.

Despite the increased prevalence of obesity, there is still a population of patients who suffer from eating disorders such as anorexia nervosa (anorexia), bulimia nervosa (bulimia), or a combination. Due to secretive behaviors and the time frame before the clinical picture of an eating disorder can be identified, the true number of affected individuals is unknown. Individuals from all demographics can develop eating disorders, which affect more than 3% of the general female population between ages 18 and 30.¹ The median age of onset is 17, with rare cases occurring after age 40.² Although more than 90% of patients diagnosed with anorexia are females, eating disorders occur in males as well. Eating disorders among athletes and models have a 10% and 20% incidence for  males and females, respectively, with bulimia occurring more frequently in this population.^1,3

The etiology for anorexia is not fully understood; however, biological, genetic, psychological, and sociocultural factors may play a role. Higher rates of anorexia have been documented among first-degree biological relatives, with an even higher association for monozygotic twins.⁴ Coexisting psychiatric illnesses such as bipolar disorder, depression, dysthymia, obsessive-compulsive disorder (OCD), and anxiety are higher among this population. Many cultural factors can add specific pressures with regard to a patient's weight or shape perception. In today's world, with an abundance of media and peer pressures, patients with anorexia have a desire to be thin and accepted.

The diagnostic criteria for anorexia are set forth by the American Psychiatric Association (APA)and are published in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR).⁵ The current diagnostic criteria for anorexia in the DSM-IV-TR are refusal to maintain a minimally normal body weight, extreme concern about gaining weight, a major aggravation in the perception of shape or size of the body, and (in a female) missing three consecutive menses. ⁵ A person is considered below minimal normal body weight if he or she weighs less than 85% of normal weight for their height and age or has a body mass index (BMI) of 17.5 kg/m² or lower.⁵

Patients with anorexia may exhibit an array of symptoms. Most notable is their low body weight, which they are embarrassed about even though they are thin. Obsessive fears about being overweight and gaining weight along with dissatisfaction over their body image may exist.⁶

Many patients with anorexia are depressed and socially withdrawn and may have obsessive-compulsive characteristics.⁵ Common traits include counting calories, weighing food, hoarding food, lying about food consumption, fasting, and examining diets excessively.^7,8 Odd eating behaviors may develop, such as taking very small bites, chewing food excessively, and pushing food around on the plate. Female patients can experience menstrual irregularities due to the extreme weight loss from not eating and/or from excessive exercise.^5-7

Patients with anorexia may use several aids to attain lower body weight. Those with diabetes may not use their insulin regimens properly due to the fear of gaining weight; therefore, many patients will omit their insulin to minimize weight gain. Some patients suffering from anorexia may also present with bulimia characteristics of binge eating or food purging. Self-induced vomiting, as well as vomiting with the use of ipecac syrup, is common. Other ways used by patients with anorexia to attain weight loss include abusive use of diuretics, laxatives, stimulants, legend or OTC diet or metabolism-enhancing products, and excessive exercise routines.

Anorexia is a very serious condition with many potential life-threatening consequences. Two of the most alarming concerns are the high relapse rates and the fact that of all psychiatric illnesses, anorexia is associated with the highest mortality rate. ^9,10 Of the patients who seek treatment, only half make a full recovery, 20% to 30% show residual symptoms, 10% to 20% continue to be severely ill, and 5% to 10% die from end organ damage and complications (TABLE 1).¹⁰

Anorexia is a complex disease involving many pathways, making it difficult to evaluate medications for treatment. There have been few randomized, double-blind, placebo-controlled trials. The difficulty of getting a well-designed trial under way is due to the low incidence of anorexia and the high drop-out rate in attempted trials; therefore, the results should be considered cautiously. Most studies involve adult women; however, young adolescent women make up the greatest population of anorexic patients. Additionally, the many comorbidities that occur with anorexia complicate treatment and patient compliance. Drug treatment alone is not enough; some form of counseling also needs to be in place for anorexic patients. 

TREATMENT
When anorexia is identified and diagnosed, treatment should begin as soon as possible to minimize the detrimental effects of the condition itself and the complications that often coexist.⁴ Early diagnosis and treatment may reduce the chance of a relapse.^4,6,8,10 According to the American Psychiatric Association, treatment goals include the following: return to and sustain a normal weight; eliminate binge eating and purging of food; motivate patients to be proactive with their heath care regimen; change negative thoughts about eating; improve self-image; address physical problems; treat psychiatric problems that may exist; administer counseling; and prevent relapse.⁴ Weight gain is the primary focus of treatment because this is a key factor in success with other treatments.^4,9,11 High relapse rates are a challenge when treating anorexic patients, and patients should be monitored regularly for relapse. In addition, patients must be educated on healthy nutrition and exercise patterns. It is essential that patients be willing to fully cooperate and have the support to follow the necessary treatment. However, getting patients to comply fully has often proved difficult for clinicians.⁶

Nonpharmacologic Strategies

Nonpharmacologic therapy for anorexia includes weight gain, nutritional rehabilitation, and counseling. The first form of treatment that many practitioners suggest is weight restoration. ^4,6 Some patients may require inpatient treatment to achieve normal weight.⁴ It has been shown that patients who regain weight to a normal BMI at inpatient treatment facilities have better long-term outcomes. ⁴ There appears to be a higher relapse rate associated with patients who leave treatment facilities before their target weight is obtained; therefore, patients should remain hospitalized until the target weight is achieved.⁴

It is strongly recommended that patients receive some form of counseling. Individual, group, or family sessions are commonly utilized.^4,10 The type of counseling that a patient undergoes depends on his or her personal needs. Family counseling appears to be the most commonly used form of psychotherapy for adolescents with anorexia, and results from studies appear promising.^4,10 It is suspected that this form of therapy is beneficial because parents may sometimes play a role in the child's development of anorexia, through either environmental or genetic aspects.⁴ Individual therapy has also shown positive results.¹⁰ Cognitive behavioral therapy (CBT), a form of individual therapy, is the most commonly used method.¹⁰ Group therapy offers a different dynamic that some patients find supportive. Group therapy can provide acceptance and camaraderie and help patients realize they are not alone.⁶ Unfortunately, there is little evidence indicating the best type of counseling. This may be attributed to the high relapse rate and patients' reluctance to comply with either initial treatment or follow-up examinations.

Pharmacologic
Direct pharmacologic treatment for anorexia currently does not exist due to the varied symptoms and range of other psychological problems that often coexist with this disorder. There are currently no FDA-approved agents for the treatment of anorexia. However, clinicians often use medications in anorexic patients to treat comorbidities and to help patients feel more comfortable with themselves. The literature is varied on the best time to begin pharmacologic treatment, and studies have not shown consistent results.⁹ It has been suggested to not begin pharmacologic treatment until weight gain has been established and instead to rely on counseling and the other nonpharmacologic treatments mentioned earlier.^6,8,12 One common problem facing patients is that they are often not willing to begin treatments or take medications.⁶ Conversely, patients may be more willing to regain weight if associated conditions are first alleviated with medication. The following sections discuss the most frequently used classes of medicines for patients with anorexia.

Antidepressant Agents
Two common comorbidities that exist in patients with anorexia are depression and obsessive-compulsive tendencies. Antidepressant medications have been used to alleviate these conditions in the hope that patients' psychological functioning will improve, resulting in weight gain.

The selective serotonin reuptake inhibitors (SSRIs) seem to be favored over the tricyclic antidepressants (TCAs) because of their side-effect profile, lower chance of overdose, and higher tolerability.^4,13

Studies have been conducted evaluating tricyclic antidepressants in the treatment of anorexia. Clomipramine was studied for anorexia in eight patients and found to have no benefits over placebo on the rate of weight gain.¹⁴ The patients on clomipramine did not gain weight faster than the control group or exhibit any long-term benefits.¹⁴ Amitriptyline was studied for change in mood, weight gain, and body perception in a double-blind, placebo-controlled trial with 25 patients. This agent showed no benefits versus placebo.¹⁵ Additionally, the patients experienced anticholinergic side effects associated with amitriptyline. Independent of side effects, TCAs should be avoided in this population if the risk for suicide is high.

Fluoxetine has been the most widely studied of the SSRIs because of its low cardiovascular and anticholinergic side effects and absence of dietary restrictions.¹⁶ Unfortunately, the results from these studies have varied. An early, open-label case series with six patients showed fluoxetine to be safe for use in underweight patients with anorexia.¹⁶ A subsequent randomized, placebo-controlled, double-blind, seven-week study with 31 patients showed fluoxetine had no benefit on weight gain or psychological state in anorexic patients.¹²

Another randomized, double-blind, placebo-controlled, year-long trial with 35 patients showed that fluoxetine was useful in the weight maintenance phase of anorexia.¹⁷ After patients had already regained weight, fluoxetine helped them retain the weight and reduce the chance of relapse. This may be attributed to the patients having a higher level of serotonin when fluoxetine was initiated. However, a recent randomized, double-blind, placebo-controlled, year-long study with 93 patients showed fluoxetine to have no benefit for weight maintenance in anorexic patients.¹⁸

Citalopram was used in a pilot study with 52 patients for three months. No difference from placebo was noticed in weight gain. However, the citalopram group did see improvements in depression, OCD symptoms, and anger.¹⁹ Sertraline was also studied in an open, controlled trial with 11 patients for 64 weeks. At a 14-week follow-up, the sertraline group showed improvements in depression, ineffectiveness, and perfectionism. Both the sertraline and control groups gained weight.²⁰

The speculated reason SSRIs, including fluoxetine, do not show consistent results is that SSRIs need some serotonin available in the brain to work, and in a malnourished anorexic patient the serotonin level is low.^6,11,17 The amino acid tryptophan is the precursor to serotonin and can only be acquired from dietary sources. Hence, a person who is not eating will not synthesize serotonin, and SSRIs will have little to no effect.

Obsessive-compulsive tendencies may occur in patients with anorexia, along with anxiety in recovering patients as they begin to see weight gain. The APA suggests the use of SSRIs for these patients.⁴ Benzodiazepines should be used cautiously in anxiety patients due to the likelihood of addiction in this population.

Antipsychotic Agents
Anorexic patients are also likely to have high rates of psychiatric conditions, including personality disorders, delusional thoughts about their body, and mood disturbances.¹³ Alterations in dopamine secretion by patients with anorexia have been reported, but the exact mechanism is still unknown.²¹ The antipsychotic agents impact dopamine levels, which may alleviate the psychiatric conditions and reduce the patient's resistance to gaining weight. The atypical antipsychotics are associated with reducing severe agitation and promoting mood stability, and weight gain, which may help anorexics with psychiatric comorbidities.²² Specifically, olanzapine and quetiapine have been used in small studies; however, larger clinical trials are lacking.

Olanzapine has been the most studied of the atypical antipsychotics for anorexia. A six-week, open-label trial with 17 patients showed that olanzapine reduced depression, anxiety, and core eating-disorder symptoms and significantly increased weight gain.²² The results from this study indicate that olanzapine may make anorexic patients less resistant to treatment and help with compliance. Another randomized, double-blind, placebo-controlled study with 30 patients supported these findings but also suggested that olanzapine does not directly cause weight gain; however, patients taking olanzapine were more willing to eat, resulting in weight gain.²¹ Additionally, many case reports have stated the positive results of weight gain during olanzapine therapy.⁹

Quetiapine can also lead to weight gain and has recently been studied for its effect on psychiatric comorbidities and weight gain in patients with anorexia.²³ An eight-week, open-label study with eight participants reported clinical improvement in depression, OCD, and BMI after eight weeks of inpatient therapy. ²³

The Role of the Pharmacist
A pharmacist counseling a patient with anorexia is in an excellent position to try to make the patient feel as comfortable with himself or herself as possible. Counseling should be done carefully and tactfully, because many recovering patients may have low self-esteem.

Many recovering patients may be adolescents and therefore may need to be properly informed and educated about the black box warning on antidepressants for increased risk of suicidal thoughts and behavior in their population. A pharmacist can explain the controversy behind this black box warning to the patient and may also need to educate the physician and caregiver of the warning. A pharmacist may also need to contact the practitioner and caregiver(s) if suicidality is noticed. Additional counseling may be performed regarding the adverse effects associated with the prescribed medications. Additionally, the antidepressant bupropion should not be used in patients with eating disorders because of the increased risk of seizures. Pharmacists should ensure that patients with eating disorders are not on this drug.

Many pharmacists are in a position within their stores to help identify abusive trends in the usage of OTC agents that can modify weight, such as herbal stimulants, diet- and metabolism-enhancing products, laxatives, enemas, and ipecac. During a drug utilization review, pharmacists can also identify inappropriate use of legend medication that can modify a person's weight. The quality of life for recovering anorexics can improve as pharmacists incorporate their knowledge of medications and compassion with patients' requirements.

Conclusion
Anorexia nervosa is an eating disorder that can affect any patient population and displays widely varying comorbidities. It is important to promote more research in this area to improve outcomes in relapse and in symptoms associated with this eating disorder. Health care providers, including pharmacists, need to be aware of the signs of anorexia nervosa so that they can identify this disorder and recommend early and appropriate treatment.

References

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