Efficacy of metformin and topiramate in prevention and treatment of second-generation antipsychotic-induced weight gain.
OBJECTIVE
To review the literature describing the efficacy of metformin and topiramate for the treatment of second-generation antipsychotic-induced weight gain.


METHODS
Articles were identified by searching the MEDLINE database (from 1949 through January 2010) using the key words metformin, topiramate, antipsychotic, weight, weight gain, and obesity.


METHODS
All randomized, placebo-controlled trials of metformin and topiramate were selected for review.


RESULTS
Weight gain due to second-generation antipsychotic use is a concern due to the risk of long-term metabolic and cardiovascular effects with these agents. These effects include obesity, hyperglycemia, and insulin resistance, all of which may contribute to diabetes and cardiovascular disease. Second-generation antipsychotics vary in the degree to which they cause weight gain, and dietary and lifestyle changes may not be feasible or sufficient in counter-acting this weight gain. Although other pharmacologic agents may be beneficial to prevent and treat antipsychotic-induced weight gain, metformin and topiramate have been the most extensively studied in this setting. Metformin acts peripherally to cause weight loss, while topiramate acts centrally. Review of 11 randomized, controlled trials demonstrates beneficial effects of metformin and topiramate in prevention and treatment of weight gain. Metformin is generally well tolerated and has been studied in pediatric patients, while topiramate is associated with more drug interactions and may possibly interfere with control of schizophrenia.


CONCLUSIONS
Data for the use of metformin and topiramate in the treatment and prevention of second-generation antipsychotic-induced weight gain are limited. Both may be effective in helping patients lose weight via mechanisms that have yet to be clearly defined. The use of metformin results in greater weight loss than topiramate, and topiramate is associated with more risks and may compromise the treatment of schizophrenia. Treatment of antipsychotic-induced weight gain with metformin may be an option after lifestyle and dietary changes have failed.
University of Illinois at Chicago College of Pharmacy, 60612, USA.
Lara K
LK
Ellinger
Heather J
HJ
Ipema
Joan M
JM
Stachnik
D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000139:chemically induced / Q000517:prevention & control; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D000077236:Topiramate; D015430:Weight Gain / Q000187:drug effects*
D019440:Anti-Obesity Agents; D014150:Antipsychotic Agents; D007004:Hypoglycemic Agents; D000077236:Topiramate; D005632:Fructose; D008687:Metformin