Effects of Modafinil on Olanzapine Weight Gain
Condition: Weight Gain
MeSH terms: Weight Gain
Study type: Interventional

Summary: 
      This study is designed as a 3 week, randomized, double blind, placebo controlled, trial.
      Olanzapine and modafinil will be titrated to 10mg and 200mg respectively. Feeding lab
      assessments will be conducted at baseline and endpoint. Assessments of hunger/satiety,
      kilocalories consumed and weight will be obtained. Plasma ghrelin and PYY3-36 levels will be
      drawn at baseline and endpoint prior to breakfast and two hours post.

      Study hypothesis: The modafinil/olanzapine group will gain less weight than the
      olanzapine/placebo group over three weeks of drug intake.
    

Detailed description: 
      Atypical antipsychotics have become the drugs of choice in the treatment of schizophrenia as
      well as acute and maintenance therapy for bipolar disorder. In addition, affective disorders
      have been found to benefit from these agents (Masan 2004). These disorders represent chronic
      conditions that require extended treatment for years if not lifetimes. In light of the ever
      widening use of the atypicals, attention must now be focused on adverse reactions that may
      limit compliance with these agents. Weight gain and sedation have proven to be associated
      with many atypicals (Allison et al. 1999; Wirshing et al. 1999) including clozapine,
      olanzapine, risperidone and quetiapine. These side effects can reduce compliance and have
      detrimental effects on patient's health over long term treatment.

      In our previous study, olanzapine and risperidone were demonstrated to affect eating
      behaviors and weight/BMI compared to placebo in a 2 week paradigm in normal healthy human
      subjects. Behaviors affected included appetite, reported calories consumed per day, and
      observed calories consumed in a feeding laboratory. No effects were seen on resting energy
      expenditure corrected for lean body weight. Also, sedation was reported in 81.3 and 75 % of
      the olanzapine and risperidone groups respectively. Sedation was the primary reason, in both
      groups, for medication dose reductions.

      Weight gain and sedation have been postulated to be associated with the blockade of central
      nervous system (CNS) histamine-1 receptors (H1) by the atypical agents (Heisler 1998;
      Wirshing et al. 1999). In light of this postulated mechanism, it is reasonable to assume that
      overcoming the H1 blockade with a histamine agonist may aid in reducing these side effects to
      a tolerable level. Thus, the following study is proposed.

      This study is designed as a randomized double blind, parallel group trial to evaluate the
      effect of modafinil (a proposed H1 agonist) vs. placebo on eating parameters, weight/BMI and
      sedation in healthy human subjects receiving olanzapine over a three week study period. This
      project utilizes the current state of the art feeding lab procedures, as reviewed by Mitchell
      and colleagues (Mitchell et al. 1998), to better characterize the effect of modafinil on
      olanzapine associated eating behavior. This project will help to determine the efficacy of
      utilizing a H1 agonist as an adjunctive medication in patients receiving atypical
      antipsychotic therapy to prevent weight gain and excess sedation.
    

Intervention name(s): Olanzapine plus modafinil; Olanzapine plus placebo
Intervention type(s): Drug; Drug
Intervention description(s): Olanzapine 10 mg/d plus modafinil 200 mg/d; Olanzapine 10 mg/d plus placebo
Other intervention name(s): Zyprexa; Provigil; Zyprexa; Provigil
Intervention MeSH terms: Olanzapine; Modafinil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: weight gain; olanzapine; atypical antipsychotic