Study of Amantadine for Weight Stabilization During Olanzapine Treatment

Summary

Weight gain associated with antipsychotic medication use is a major side effect that limits the tolerability of these drugs. This often significant weight gain adversely affects health, increasing risks for developing cardiovascular disease, diabetes, sleep apnea, cancers of the colon, kidneys, uterus, endometrium and esophagus and osteoarthritis. Beasley and colleagues (1997) reported that 40.5% of olanzapine-treated patients gained more than 7% of baseline weight. Much of the olanzapine induced weight gain occurs early in treatment, and antipsychotic-naïve and young patients (Woods et al., 2002) are particularly vulnerable to this side effect. One of the most promising medications to aid weight loss in patients taking olanzapine is amantadine.

Attempts at preventing weight gain are expected to be more successful than attempts to reverse it once it occurs. It is now common clinical practice to educate all patients beginning treatment with olanzapine, and other antipsychotics, about healthy eating and the need for exercise. However, despite this effort, weight gain in this population continues. Beginning a weight-stabilizing medication after a low threshold of weight gain has occurred may have significant impact on patients' health and their willingness to continue to take antipsychotics.

We propose to investigate the efficacy of amantadine as a weight-stabilizing agent in a population of first-episode psychotic subjects just beginning treatment with antipsychotic agents. This population is generally young and medically healthy, without contraindications to amantadine. They are often of normal body mass index and without obesity-related medical problems. They have much to gain in preventing the weight gain which so often progresses steadily over the course of treatment, is difficult to reverse and results in significant morbidity and mortality. Additionally, the first episode psychotic population tends to take fewer concomitant psychiatric medications. This is important since these medications may cause weight gain (long term use of mirtazapine, lithium, depakote) or weight loss (short term use of SSRI's) which could confound the effectiveness of amantadine to combat weight gain.

Conditions

• Psychotic Disorder
• Schizophreniform Disorder
• Schizophrenia
• Schizoaffective Disorder
• Mood Disorders With Psychotic Features

Interventions

DRUG

Olanzapine, Amantadine

Olanzapine continuing as clinically indicated, Amantadine 100 mg tid

DRUG

Olanzapine and placebo

Olanzapine continuing as clinically indicated

Sponsors & Collaborators

• Eli Lilly and Company

  collaborator INDUSTRY

• University of North Carolina, Chapel Hill

  lead OTHER

Principal Investigators

• Karen A Graham, MSc MD · University of North Carolina, Chapel Hill

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-05-31

Primary Completion

2009-09-30

Completion

2009-09-30

Countries

• United States

Study Locations