Copyright of Informa UK Ltd. Printing and distribution strictly prohibited Review 10.1517/14740338.5.4.523 © 2006 Informa UK Ltd ISSN 1474-0338 523 Cardiovascular & Renal The effect of antidepressants on lipid homeostasis: a cardiac safety concern? Roger S McIntyre † , Joanna K Soczynska, Jakub Z Konarski & Sidney H Kennedy † University of Toronto, Department of Psychiatry, Toronto, ON, Canada Objective: The authors sought to summarise and synthesise results from investi- gations which report on the effect of antidepressants on serum lipid homeos- tasis. Method: The authors conducted a MedLine search of all English-language articles from 1966 to March 2006 using the search terms: major depressive dis- order, bipolar disorder, lipids, triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein, and the non-proprietary names of conventional anti- depressants indicated for the treatment of major depressive disorder in North America as of March 2006. The search was supplemented with a manual review of retrieved articles for any further citations reporting the effects of antide- pressants on lipid homeostasis. Results: Despite the paucity of well-character- ised investigations, the unfavourable effect of weight gain promoting antidepressants (e.g., tricyclics, mirtazapine) on serum lipid parameters (i.e., triglycerides and low-density lipoprotein cholesterol) is a consistent find- ing. Weight-neutral antidepressants (e.g., bupropion, venlafaxine, duloxetine), however, are less likely to disrupt the lipid milieu. A weight-independent effect on lipid homeostasis is less consistently reported. Conclusion: Some antidepres- sants unfavourably influence the lipid milieu; mediating factors other than weight gain are not well-established. Pivotal studies evaluating the therapeu- tic index of antidepressants need to systematically collect and report data on the lipid effects of antidepressants. Keywords: antidepressant, bipolar disorder, bupropion, cholesterol, depression, duloxetine, lipid homeostasis, mirtazapine, selective serotonin re-uptake inhibitor (SSRI), triglyceride, venlafaxine Expert Opin. Drug Saf. (2006) 5(4):523-537 1. Introduction Major depressive disorder is a highly prevalent, often chronic medical disorder largely diagnosed and treated in primary-care settings [1]. Currently, major depres- sive disorder is a leading cause of disability globally, and there is increasing evi- dence that it is an important risk factor for the development of major medical disorders such as coronary artery disease (CAD ) [2]. Mortality studies indicate that CAD is the most frequent cause of premature mortality in individuals with mood and psychotic disorders [3,4]. Dyslipidaemia is an independent risk factor for incident and recurrent CAD [5]. T he T hird Report of the National Cholesterol Education Expert Panel (NCEP-III) indicates that increased low-density lipoprotein cholesterol (LDL-C) is the primary factor predicting CAD risk [5]. A direct association between LDL-C (and total cho- lesterol), and new-onset CAD, or recurrent coronary events, has been reported in population-based studies [6]. T he CAD risk associated with atherogenic LDL-C lev- els (> 100 mg/dl; 2.59 mmol/l) is greater in the presence of other established CAD 1. Introduction 2. Methods 3. Results 4. Summary and conclusion 5. Expert opinion To comment on this article, please contact: emma.quigley@informa.com