The effect of antidepressants on lipid homeostasis: a cardiac safety concern?

Abstract

Objective: The authors sought to summarise and synthesise results from investigations which report on the effect of antidepressants on serum lipid homeostasis. Method: The authors conducted a MedLine search of all English-language articles from 1966 to March 2006 using the search terms: major depressive disorder, bipolar disorder, lipids, triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein, and the non-proprietary names of conventional antidepressants 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 antidepressants on lipid homeostasis. Results: Despite the paucity of well-characterised 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 finding. 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 antidepressants unfavourably influence the lipid milieu; mediating factors other than weight gain are not well-established. Pivotal studies evaluating the therapeutic 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

Notes

High risk, defined as a net of ≥ 2 CHD risk factors, leads to more vigorous intervention in primary prevention. Age (defined differently for men and for women) is treated as a risk factor because rates of CHD are higher in the older than in the young, and in men than in women of the same age. Obesity is not listed as a risk factor because it operates through other risk factors that are included (hypertension, hyperlipidaemia, and decreased HDL cholesterol, as well as diabetes mellitus, which is treated as a CHD equivalent, but it should be considered a target for intervention. Physical inactivity is not listed as a risk factor to modify treatment goals for LDL cholesterol, but it too should be considered a target for intervention, and physical activity is recommended as desirable for everyone. High risk due to CHD or its equivalents is addressed directly in the algorithm.

*Confirmed by measurements on several occasions.

^‡If the HDL-cholesterol level is ≥ 60 mg/dl, subtract one risk factor (because high HDL-cholesterol levels decrease CHD risk). CHD: Coronary heart disease; HDL: High-density lipoprotein; LDL: Low-density lipoprotein. Box adapted from the Third Report of the National Cholesterol Education Programme (NCEP) [5].