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Management of atypical antipsychotic drug-induced weight gain: focus on metformin.
Pharmacotherapy. 2009 Jun; 29(6):725-35.P

Abstract

Many patients taking atypical antipsychotic drugs will experience weight gain. Evidence suggests that long-term treatment with these agents decreases glucose effectiveness, alters satiety signals, creates hormonal resistance to satiety control, and may have a direct effect on hypothalamic appetite centers. The serotonin(2c-) and histamine(1)-receptor antagonism of atypical antipsychotics may also lead to weight gain. Several nonpharmacologic and pharmacologic methods have been used to address this adverse effect, with varying success. Metformin is an antidiabetic drug that has been shown to cause weight loss in patients with diabetes mellitus, as well as in some individuals without diabetes. To evaluate whether metformin can decrease weight gain induced by atypical antipsychotics in patients without diabetes, we conducted a literature search using the MEDLINE database (1970-October 2008) and clinicaltrials.gov Web site for relevant trials. Overall, 14 articles were identified for inclusion; review articles, case reports, and open-label studies were excluded. Thus, eight double-blind, placebo-controlled studies were reviewed; both pediatric and adult trials were included. Metformin has several advantages, including ease of use and a favorable safety profile. Although lactic acidosis was not reported in any of the studies reviewed, this potentially rare but severe adverse effect must be considered when prescribing this agent. Limited data suggest that metformin may attenuate weight gain in both adult and adolescent patients taking atypical antipsychotics. However, most of the trials included foreign populations, were only 12-16 weeks in duration, and the dosage of metformin may not have been adequately titrated. Although the study results do not provide clear substantial evidence that metformin, as an adjuvant to atypical antipsychotic use, will decrease weight gain and improve metabolic effects, they are encouraging. Additional studies of longer duration that include behavioral therapy and special diets should be conducted in patients from the United States. Currently, the drug is being used as a secondary or tertiary intervention, and its use may be considered in patients with a personal and/or family history of obesity or metabolic dysfunction, and in subjects who have rapid weight gain early in antipsychotic treatment.

Authors+Show Affiliations

Pharmacy Services, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030, USA. lisaj.miller@va.gov

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19476423

Citation

Miller, Lisa J.. "Management of Atypical Antipsychotic Drug-induced Weight Gain: Focus On Metformin." Pharmacotherapy, vol. 29, no. 6, 2009, pp. 725-35.
Miller LJ. Management of atypical antipsychotic drug-induced weight gain: focus on metformin. Pharmacotherapy. 2009;29(6):725-35.
Miller, L. J. (2009). Management of atypical antipsychotic drug-induced weight gain: focus on metformin. Pharmacotherapy, 29(6), 725-35. https://doi.org/10.1592/phco.29.6.725
Miller LJ. Management of Atypical Antipsychotic Drug-induced Weight Gain: Focus On Metformin. Pharmacotherapy. 2009;29(6):725-35. PubMed PMID: 19476423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Management of atypical antipsychotic drug-induced weight gain: focus on metformin. A1 - Miller,Lisa J, PY - 2009/5/30/entrez PY - 2009/5/30/pubmed PY - 2009/8/7/medline SP - 725 EP - 35 JF - Pharmacotherapy JO - Pharmacotherapy VL - 29 IS - 6 N2 - Many patients taking atypical antipsychotic drugs will experience weight gain. Evidence suggests that long-term treatment with these agents decreases glucose effectiveness, alters satiety signals, creates hormonal resistance to satiety control, and may have a direct effect on hypothalamic appetite centers. The serotonin(2c-) and histamine(1)-receptor antagonism of atypical antipsychotics may also lead to weight gain. Several nonpharmacologic and pharmacologic methods have been used to address this adverse effect, with varying success. Metformin is an antidiabetic drug that has been shown to cause weight loss in patients with diabetes mellitus, as well as in some individuals without diabetes. To evaluate whether metformin can decrease weight gain induced by atypical antipsychotics in patients without diabetes, we conducted a literature search using the MEDLINE database (1970-October 2008) and clinicaltrials.gov Web site for relevant trials. Overall, 14 articles were identified for inclusion; review articles, case reports, and open-label studies were excluded. Thus, eight double-blind, placebo-controlled studies were reviewed; both pediatric and adult trials were included. Metformin has several advantages, including ease of use and a favorable safety profile. Although lactic acidosis was not reported in any of the studies reviewed, this potentially rare but severe adverse effect must be considered when prescribing this agent. Limited data suggest that metformin may attenuate weight gain in both adult and adolescent patients taking atypical antipsychotics. However, most of the trials included foreign populations, were only 12-16 weeks in duration, and the dosage of metformin may not have been adequately titrated. Although the study results do not provide clear substantial evidence that metformin, as an adjuvant to atypical antipsychotic use, will decrease weight gain and improve metabolic effects, they are encouraging. Additional studies of longer duration that include behavioral therapy and special diets should be conducted in patients from the United States. Currently, the drug is being used as a secondary or tertiary intervention, and its use may be considered in patients with a personal and/or family history of obesity or metabolic dysfunction, and in subjects who have rapid weight gain early in antipsychotic treatment. SN - 1875-9114 UR - https://www.unboundmedicine.com/medline/citation/19476423/Management_of_atypical_antipsychotic_drug_induced_weight_gain:_focus_on_metformin_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=19476423.ui DB - PRIME DP - Unbound Medicine ER -