By Jennifer Reid, MD (bio)
Dr. Reid is a psychiatrist in Philadelphia and an adjunct faculty member in the department of psychiatry at the University of Pennsylvania in Philadelphia, PA. Her full bio is available HERE and her private practice website is www.jenniferreidmd.com.
One unfortunate side effect of many of our atypical antipsychotics is metabolic changes, including elevated blood sugar, weight gain, and elevated cholesterol, particularly triglycerides. For example:
– Olanzapine (brand name Zyprexa) can increase triglycerides by about 40% over 12 weeks (Sheitman et al., 1999) with two-thirds of patients having elevated triglycerides on this medication (Melkersson KI et al., 2000).
– Also, over 5 years of treatment, clozapine can lead to a doubling of the mean serum triglycerides level (Henderson et al., 2000).
Mainly due to increasing rates of obesity and diabetes mellitus, both hypertriglyceridemia and very high triglycerides are becoming increasingly prevalent in the United States, even in patients not on second-generation antipsychotics, (Skulas-Ray et al., 2019).
Patients should be referred to their primary care physicians for the management of elevated triglycerides.
On this page, I will discuss only one aspect of managing elevated triglycerides—the use of omega-3 fatty acids not only for their mental health benefits but also for reducing elevated triglyceride levels.
Do omega-3 fatty acids treat hypertriglyceridemia?
In 2019, the American Heart Association issued a statement about the role of 4 g/day of omega-3 fatty acids in patients with increased serum triglycerides, either as monotherapy or along with other lipid-lowering agents (Skulas-Ray et al., 2019).
In patients with other risk factors like atherosclerotic disease and diabetes mellitus, the statement noted omega-3 fatty acids to be a generally safe and effective treatment option for lowering elevated serum triglyceride levels and decreasing adverse cardiovascular events.
How important or useful is this intervention? How much of a difference could it make? Could such a simple measure reduce serious adverse events like stroke, heart attacks, and so on?
This recommendation by the American Heart Association was supported by the results of an important clinical trial called REDUCE-IT (Bhatt, 2019) that found that when 4 g/day of omega-3 fatty acids was added to ongoing treatment with a statin, there was a:
– 25% reduction in the risk of major adverse cardiovascular events, including
– about a 30% reduction in stroke, and
– a 30% reduction in myocardial infarction (MI).[Editor: A 25% to 30% reduction in the risk of such serious events is a massive benefit, don’t you think?]
Potential side effects of omega-3 fatty acids
In addition to gastrointestinal side effects, there was a trend towards increased bleeding risk in patients who received omega-3 fatty acids in the REDUCE-IT study. Even though this finding was not statistically significant (that is, it may have been by chance), it is known from previous data that omega-3 fatty acids can increase the risk of bleeding. So, it makes sense to avoid high doses of omega-3 fatty acids in patients with a history of serious bleeding or a higher than usual bleeding risk.
Overall, this AHA recommendation is helpful because we are regularly monitoring these metabolic changes in our patients, and could potentially provide benefit for both their cardiovascular health, as well as their depression, by prescribing high-quality omega-3 fatty acids to treat hypertriglyceridemia. Although monitoring from a primary care provider is also important, we may often be the front line for many of our patients who are at high risk for negative cardiovascular outcomes.
Exactly which products should be recommended will be discussed on other pages on this website.
Monitoring for metabolic side effects in children and adolescents on a second-generation (atypical) antipsychotic
Bhatt DL. REDUCE-IT. Eur Heart J. 2019 Apr 14;40(15):1174-1175. doi: 10.1093/eurheartj/ehz179. PubMed PMID: 30982067.
Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry 2000;157:975-981. PubMed PMID: 10831479.
Melkersson KI, Hulting AL, Brismar KE. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychosis. J Clin Psychiatry 2000;61:742-749. PubMed PMID: 11078035.
Sheitman BB, Bird PM, Binz W, Akinli L, Sanchez C. Olanzapine-induced elevation of plasma triglyceride levels. Am J Psychiatry 1999;156:1471-1472. PUbMed PMID: 10484969
Skulas-Ray AC, Wilson PWF, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, Jacobson TA, Engler MB, Miller M, Robinson JG, Blum CB, Rodriguez-Leyva D, de Ferranti SD, Welty FK; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation. 2019 Aug 19:CIR0000000000000709. doi: 10.1161/CIR.0000000000000709. [Epub ahead of print] PubMed PMID: 31422671.
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