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Metabolic side effects of antipsychotic drug treatment--pharmacological mechanisms.
Pharmacol Ther. 2010 Jan; 125(1):169-79.P&T

Abstract

Obesity and metabolic syndrome, with increased risk of eventual cardiovascular disease and type II diabetes, are significant problems for patients receiving antipsychotic drugs and are likely contribute to their decreased life expectancy. Several drug-related mechanisms may contribute to these problems, including effects both influencing food intake and on glucose and lipid metabolism. The metabolic consequences of different antipsychotic drugs vary substantially; these variations reflect differences in receptor pharmacology and provide clues as to the underlying pharmacological mechanisms. The two drugs with the greatest effects on body weight, olanzapine and clozapine, also have high affinity for the 5-HT2C and histamine H1 receptors, which implicate these receptors in antipsychotic-induced weight gain, while peripheral M3 muscarinic receptor antagonism as well as central 5-HT2C effects may contribute to obesity-independent diabetes. Other receptor mechanisms may have additive or synergistic effects; dopamine D2 receptor antagonism can enhance 5-HT2C-mediated effects on food intake, as well as influencing lipid and glucose metabolism via disinhibition of prolactin secretion. Pharmacogenetic associations of drug-induced weight gain with 5-HT2C receptor and leptin gene polymorphisms, among others, have provided further clues. Elevated leptin secretion in the absence of a decrease in food intake indicates drug-induced leptin insensitivity in the hypothalamus. The minimal weight gain seen with ziprasidone and aripiprazole may reflect their having further pharmacological effects that protect against changes in food intake and related metabolic factors. Understanding the pharmacology of metabolic consequences of current antipsychotic drug treatment is clearly the key to developing improved pharmacotherapies that avoid these problematic and limiting adverse effects.

Authors+Show Affiliations

Department of Psychiatry, Queen's University Belfast, Belfast BT9 7BL, UK. g.reynolds@qub.ac.ukNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19931306

Citation

Reynolds, Gavin P., and Shona L. Kirk. "Metabolic Side Effects of Antipsychotic Drug Treatment--pharmacological Mechanisms." Pharmacology & Therapeutics, vol. 125, no. 1, 2010, pp. 169-79.
Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment--pharmacological mechanisms. Pharmacol Ther. 2010;125(1):169-79.
Reynolds, G. P., & Kirk, S. L. (2010). Metabolic side effects of antipsychotic drug treatment--pharmacological mechanisms. Pharmacology & Therapeutics, 125(1), 169-79. https://doi.org/10.1016/j.pharmthera.2009.10.010
Reynolds GP, Kirk SL. Metabolic Side Effects of Antipsychotic Drug Treatment--pharmacological Mechanisms. Pharmacol Ther. 2010;125(1):169-79. PubMed PMID: 19931306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolic side effects of antipsychotic drug treatment--pharmacological mechanisms. AU - Reynolds,Gavin P, AU - Kirk,Shona L, Y1 - 2009/11/17/ PY - 2009/10/23/received PY - 2009/10/23/accepted PY - 2009/11/26/entrez PY - 2009/11/26/pubmed PY - 2010/3/2/medline SP - 169 EP - 79 JF - Pharmacology & therapeutics JO - Pharmacol Ther VL - 125 IS - 1 N2 - Obesity and metabolic syndrome, with increased risk of eventual cardiovascular disease and type II diabetes, are significant problems for patients receiving antipsychotic drugs and are likely contribute to their decreased life expectancy. Several drug-related mechanisms may contribute to these problems, including effects both influencing food intake and on glucose and lipid metabolism. The metabolic consequences of different antipsychotic drugs vary substantially; these variations reflect differences in receptor pharmacology and provide clues as to the underlying pharmacological mechanisms. The two drugs with the greatest effects on body weight, olanzapine and clozapine, also have high affinity for the 5-HT2C and histamine H1 receptors, which implicate these receptors in antipsychotic-induced weight gain, while peripheral M3 muscarinic receptor antagonism as well as central 5-HT2C effects may contribute to obesity-independent diabetes. Other receptor mechanisms may have additive or synergistic effects; dopamine D2 receptor antagonism can enhance 5-HT2C-mediated effects on food intake, as well as influencing lipid and glucose metabolism via disinhibition of prolactin secretion. Pharmacogenetic associations of drug-induced weight gain with 5-HT2C receptor and leptin gene polymorphisms, among others, have provided further clues. Elevated leptin secretion in the absence of a decrease in food intake indicates drug-induced leptin insensitivity in the hypothalamus. The minimal weight gain seen with ziprasidone and aripiprazole may reflect their having further pharmacological effects that protect against changes in food intake and related metabolic factors. Understanding the pharmacology of metabolic consequences of current antipsychotic drug treatment is clearly the key to developing improved pharmacotherapies that avoid these problematic and limiting adverse effects. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/19931306/Metabolic_side_effects_of_antipsychotic_drug_treatment__pharmacological_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(09)00214-9 DB - PRIME DP - Unbound Medicine ER -