Chris Aiken, MD. Editor-in-Chief of The Carlat Psychiatry Report. Assistant Professor, NYU Langone Department of Psychiatry. Practicing psychiatrist, Winston-Salem, NC.
Garrett Rossi, MD. Adult psychiatrist, AtlantiCare Regional Medical Center, Pomona, NJ.
Dr. Aiken and Dr. Rossi have no financial relationships with companies related to this material.
Anorexia nervosa is notoriously difficult to treat. While psychotherapy is the treatment of choice, medications can play a role, and in this article, we’ll take a look at some options—including a mineral that often gets overlooked: zinc.
Antipsychotics seem like an intuitive choice for anorexia given their potential to increase weight and appetite. However, the clinical trials of antipsychotics—which date back to the early 1960s—have not yielded favorable results. Olanzapine, risperidone, and amisulpride did not bring about significant improvements in BMI or body image scores in a meta-analysis of eight small randomized controlled trials (RCTs) (Lebow J et al, Int J Eat Disord 2013;46(4):332–339).
Antidepressants met a similar fate. In the 1980s, four small randomized controlled trials found little benefit with tricyclics. Anorexia also raises the risks of arrhythmias on tricyclics, so they are best avoided in these patients. The SSRIs did not fare any better. Studies of both fluoxetine and citalopram failed to provide a meaningful benefit over placebo.
The results look more positive with cyproheptadine, an antihistamine whose pharmacodynamic profile resembles the antidepressant mirtazapine. Both cyproheptadine and mirtazapine block histamine and serotonin-2 receptors, improving sleep while causing similar side effects of fatigue and weight gain. Both are used in medical conditions that lower appetite, but only cyproheptadine has studies in anorexia (Halmi KA et al, Arch Gen Psychiatry 1986;43(2):177–181).
In two separate RCTs, researchers randomized hospitalized patients with anorexia to receive cyproheptadine, amitriptyline, or placebo (total n = 111). Cyproheptadine improved weight gain and depressive symptoms after one to three months, but only in patients without bulimic features (target dose 8 mg QID, starting at 2 mg TID and titrated over three weeks).
Another novel approach is dronabinol, a synthetic cannabinoid that the FDA has approved for weight loss in HIV/AIDS. This medication lacks RCTs in anorexia but was superior to placebo in terms of weight gain in one small crossover study (Andries A et al, Int J Eating Disord 2014;47(1):18–23).
Zinc levels are often low in patients with anorexia due to inadequate intake, and this deficiency creates a vicious cycle by lowering appetite even further. One RCT tested a daily 100 mg dose of zinc in 35 females with anorexia in the inpatient setting. The rate of increase in BMI for the zinc group was twice that of the placebo group (Birmingham CL et al, Int J Eat Disord 1994;15(3):251–255). Although zinc is available over the counter, adherence seems to improve when it is written as a prescription. The typical dose is zinc gluconate 100 mg daily. The studies reported no adverse effects from zinc supplementation.
Psychotherapy is the mainstay of treatment for anorexia, and there are several effective options to guide patients toward. Cognitive behavioral therapy (CBT), focal psychodynamic therapy, and interpersonal therapy are more successful in adults, and certain types of family therapies have better outcomes in adolescents. Family therapies go by an array of names (eg, systemic family therapy, family-based treatment, the Maudsley model), but they all have one thing in common. They don’t scrutinize family dynamics to find the root cause of the problem. Instead, they empower parents to refeed their child. Later, they work on family dynamics or adolescent development as weight is restored.
On average, patients gain about 1.5 lbs a week with inpatient psychotherapy and 0.25–0.5 lb a week with outpatient psychotherapy. Mild cases may recover within six months of therapy, while it may take a year or more to restore weight in patients with severe anorexia (Zeeck A et al, Front Psychiatry 2018;9:158).
Nutritional counseling is helpful and sometimes necessary. A dietician can suggest meal plans and supplements and clarify caloric requirements and nutritional deficiencies for the patient and clinical team. Patients participating in CBT nutritional counseling can also assist with self-monitoring of dietary patterns and identifying and avoiding cues to restrict, binge, or purge.
In anorexia, focus on guiding the patient to an effective psychotherapy and an appropriate level of care. Zinc supplementation and cyproheptadine may be beneficial, but pharmacologic options are few and the evidence supporting them is very preliminary.
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