Risperidone for Treatment of Anorexia Nervosa: A Pilot Study

Results did not echo those from
earlier studies with olanzapine.

As yet, no psychotropic drugs have been approved for treatment of anorexia nervosa (AN) in adults or adolescents. “Atypical” neuroleptic drugs, such as risperidone and olanzapine, are potent serotonin antagonists, in addition to binding to dopamine at 4 receptor sites. Two randomized controlled studies of olanzapine for AN in adult female subjects have been conducted thus far. In the first, weight gain increased and depression and obsession scores decreased with treatment (Psychol Med 2011;41:2177).

A second study, which included a cognitive behavioral therapy (CBT) arm, found no benefits for olanzepine with regard to changes in weight but did report improvements in compulsivity, depression, and aggressiveness for the group that received CBT and olanzapine (Expert Opin Pharmacother 2003;4:1659).

Dr. Jennifer Hagman and colleagues at the University of Colorado School of Medicine and Children’s Hospital Colorado, Denver, designed a double-blind, placebo-controlled pilot study to assess the efficacy and safety of risperidone for treating teens and young adults with AN (J Am Acad Child Adolesc Psychiatry 2011;915). A second goal was to determine if risperidone could shorten the period required for a patient to reach 90% of ideal body weight (IBW). The study also sought to explore whether risperidone could be tolerated by AN patients and if its use would reduce anxiety during weight restoration.

The researchers invited all patients receiving care in the eating disorders program from August 2004 to September 2008 and who met the inclusion criteria to participate in the study. Inclusion criteria included a primary diagnosis of AN, female gender, age 12 to 21 years (those under 18 had parental consent for participation), and active participation in the eating disorders program. Comorbid diagnoses, such as depression and anxiety disorder, and bulimia nervosa were allowed as long as the primary diagnosis was AN. The diagnosis of AN was established by DSM-IV criteria, a comprehensive clinical evaluation, and agreement upon the diagnosis by a child and adolescent psychiatrist and a specialist in adolescent medicine.

All subjects were initially admitted to the inpatient or day treatment level of care and received care as usual during the study; this included individual, family and group psychotherapy, nutritional counseling, medical management, and individualized meal plans for weight restoration. The program targeted 90% of IBW for subjects with secondary amenorrhea and 100% of IBW for subjects with primary amenorrhea. Target rates of weight gain were 0.2 kg/day in the inpatient level of care and 0.1 kg/day in day treatment.

The authors point out that a significant number of AN patients who present for treatment of AN are also taking an antidepressant, usually a serotonin-selective reuptake inhibitor. Although it would have been ideal to have subjects take only the study medicine, patients who were already taking a antidepressant were allowed to enroll and to continue their antidepressant if they had been on a stable dose for longer than 1 week before entering the study and did not wish to discontinue the medication.

Risperidone group. Initially, 19 patients were allocated to receive risperidone treatment; one patient dropped out of the group after her parents requested active medication. The drug was started at 0.5 mg daily and titrated upward weekly in 0.5-mg doses to a maximum dose of 4.0 mg.

Placebo group. Twenty-two patients were randomized to the placebo group and all continued throughout the study. These subjects received 3 mg of placebo for a mean of 9 weeks.

Results did not confirm the initial hypotheses

During the first 7 weeks of the study, those in the risperidone group had a significant decrease on the Eating Disorders Inventory 2 (EAT-2) Drive for Thinness subscale, but this difference faded by the end of the study. The EAT-2 Interpersonal Distrust subscale score also significantly decreased among the risperidone group, and prolactin levels were significantly elevated (37.7 ng/mL versus 5.5 ng/mL among the placebo group).

At the end of the study, the authors could show no significant benefits from adding risperidone during the weight-restoration phase of care. Not only did subjects on risperidone not gain weight any more quickly than did subjects on placebo, there was a trend for those treated with risperidone to experience an increase in resting energy expenditure, or REE. This was a paradoxical finding, according to the authors, because patients taking risperidone for other reasons often have significant weight gain. Although increased appetite and increased food intake seem to be the explanation in cases of weight gain, the authors think it may also be possible that risperidone affects the body’s metabolic rate.