Abstract
The aim of this article is to review related literature on management of hyperphagia and impulsive behaviors in Prader–Willi syndrome (PWS) that includes either naltrexone or bupropion. In this article we also discuss a case of a 13-year-old female with PWS struggling with some behavioral and psychiatric symptoms.
To the Editor:
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Case Report
We present a case of a 13-year-old female in 8th grade receiving special education services. The patient presented with difficulties in impulse control and was found to have PWS. She has history of multiple psychiatric hospitalizations. She has history of trials on multiple psychotropic medications with not much improvement. Contrave was added to her regimen of an alpha 2 agonist and an atypical antipsychotic. Her target clinical symptoms were impulsivity, inattention, physical aggression, and overeating behavior. A total daily dosage of two Contrave 8 mg/90 mg tablets twice daily (32 mg/360 mg) was reached at week 4. Perphenazine was discontinued.
Since being on Contrave she started doing well with improved eating habits and decrease in aggression.
Before starting Contrave, her weight was 162.1 lb, height 148.5 cm, and body mass index (BMI) of 33.9, and after 6 weeks of trial her weight was 161.7 lb, height 148.6 cm, and BMI of 32.7.
Hyperphagia and Impulsive Behavior
Behavioral characteristics in PWS include excessive interest in food, skin picking, and difficulty with changes in routine, temper tantrums, obsessive compulsive behaviors, and mood fluctuations (Ho and Dimitropoulos 2010; Banga and Connor 2012). The underlying molecular mechanisms that contribute to the excessive weight gain and hyperphagia in PWS remain poorly understood (Ho and Dimitropoulos 2010; Miller and Strong 2015; Miller et al. 2015).
Management and Treatment Options
There are some FDA-approved medications such as naltrexone and bupropion, which may potentially improve satiety or help ameliorate obesity and impulsive behavior in individuals with PWS (Ho and Dimitropoulos 2010; Miller et al. 2015).
Naltrexone and Bupropion Combination Treatment/Contrave
Naltrexone and bupropion were compared in studies for weight loss and as a combination treatment as well. Obese adult patients taking naltrexone and bupropion combination treatment (NB) had a greater weight loss than patients taking individual monotherapies of the drugs or a placebo. The FDA approved a naltrexone/bupropion combination marketed under the name Contrave for treatment of obesity in September 2014 after moderately successful results of several randomized double bind clinical trials. Subjects chosen for the trials were between ages 18 and 45 with a BMI ranging from 30 to 40.
By phase 3 of Contrave trials, daily dose of the combination therapy was 32 mg/day of naltrexone sustained release plus 360 mg/day of bupropion sustained release (NB32). Results showed weight loss as early as week 4 in subjects taking the combination therapy compared to subjects taking monotherapies of each drug or a placebo. The weight loss was sustained for at least 56 weeks. Most frequent side effects were nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
Contrave and Management of Hyperphagia and Impulsive Behavior in PWS
Naltrexone and bupropion have independent actions in the brain's reward system and POMC (pro-opiomelanocortin) neurons of the hypothalamus, but the systemic effects of the combination produce a synergistic effect of decreasing food intake and weight loss over time. The mechanism of NB combination therapy may also treat impulsive behavior in PWS. An ongoing 2015 case mentions Contrave as a treatment of hyperphagia and impulsive behaviors of a female adolescent with PWS.
Since the start of Contrave, the patient is doing well and has mostly been clinically stable.
The neurological and psychiatric reactions of Contrave, naltrexone, and bupropion treatment need to be examined further in long-term clinical trials of PWS patients as well as involving pediatric and adolescent subjects.
Disclosures
M.R.P., R.S., and S.O. have no conflicts of interest. M.R.P. is the 1st year child fellow at the Institute of Living. R.S. is the program director at the Institute of Living. S.M. is the associate program director. She has research grants from Pfizer, Forest, Sunovian, and SyneuRx. S.O. is a graduate of St. George's medical school.