Phenylpropanolamine Appears Not to Promote Weight Loss in Patients With Schizophrenia Who Have Gained Weight During Clozapine Treatment

Background: Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight.

Method: This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained>10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly.

Results: Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t=0.219, df=10, p=.831). There was no significant change in either the total PANSS scores (t=-0.755, df=10, p=.468), the positive or negative symptom cluster scores, or any of the remaining variables.

Conclusion: Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.