An exploration of the effect of modafinil on olanzapine associated weight gain in normal human subjects.
BACKGROUND
Weight gain has been associated with many second generation antipsychotics (SGAs). A variety of theories have been put forward as to the etiology of SGA-associated weight gain. Modafinil possesses pharmacologic effects that could influence the weight gain associated with SGAs. The objective of this trial was to determine the effect of modafinil on olanzapine-associated weight gain.


METHODS
This study was a 3-week, randomized, double-blind, placebo-controlled trial. All subjects received olanzapine titrated to 10 mg/day. Concurrently, subjects were randomized to receive modafinil titrated to 200 mg/day or placebo. Weight and feeding lab assessments were conducted at baseline and endpoint.


RESULTS
Fifty subjects were enrolled in the study with 20 subjects per group completing the trial. The primary outcome variable was change in the body mass index (BMI) over the 3 weeks of the trial. Increases in BMI were observed in both groups. However, analysis of covariance, controlled for baseline BMI, revealed that the olanzapine/placebo group had a greater increase in BMI at end point compared with the olanzapine/modafinil group (.89 +/- .59 vs. .47 +/- .50 kg/m(2), p < .05). When controlled for gender, the comparison showed a significant difference between groups at week 1 but not at weeks 2 or 3.


CONCLUSIONS
The results of this trial should not be extrapolated to clinical practice at this time. These data do serve to support further evaluation in a patient population to determine if the weight modifying effect of modafinil can be demonstrated over a longer period of time.
Roerig
James L
JL
University of North Dakota School of Medicine and Health Sciences, 120 South 8th Street, Fargo, ND 58107-1415, USA. jroerig@nrifargo.com
Steffen
Kristine J
KJ
Mitchell
James E
JE
Crosby
Ross D
RD
Gosnell
Blake A
BA
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D015992:Body Mass Index; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D000077408:Modafinil; D000077152:Olanzapine; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D001569:Benzodiazepines; D000077152:Olanzapine; D000077408:Modafinil