Does trazodone affect cholesterol? (3+ facts)

In this article, we will discuss whether trazodone affects cholesterol, how trazodone affects cholesterol, what research suggests, and what the benefits and harms of this effect are.

Does trazodone affect cholesterol?

Yes, trazodone may affect the levels of cholesterol in patients taking it to treat their mental health conditions. While the direct impact of trazodone on cholesterol is not fully understood, some studies suggest a potential connection. 

Trazodone is a serotonin modulator that works by inhibiting the serotonin transporter and serotonin type-2 receptors and, as a result, increasing serotonin levels in the brain. It is mainly prescribed for the treatment of major depressive disorders (MDD), anxiety, and insomnia. (1)

Cholesterol is a lipophilic molecule crucial for various bodily functions, and its levels are typically measured through blood tests that evaluate total cholesterol, LDL (low-density lipoprotein), HDL (high-density lipoprotein), and triglycerides. (2)

How does trazodone affect cholesterol?

Research on the specific mechanisms through which trazodone may influence cholesterol levels is limited. However, trazodone interacts with serotonin receptors in the brain, affecting serotonin levels, which have been linked to cholesterol metabolism. Some studies suggest that an increase in serotonin levels may enhance lipid metabolism and contribute to lower cholesterol levels. (3)

One study indicated that the reductions in cholesterol levels are due to trazodone’s ability to inhibit the DHCR7 enzyme, which is crucial for cholesterol biosynthesis. (6)

What does research suggest?

Research on the impact of trazodone on cholesterol is not extensive. A clinical trial on trazodone-related laboratory abnormalities concluded that after treatment with trazodone for six weeks, there was a marked reduction in cholesterol levels. (4)

Another clinical trial was done to use trazodone to treat atherosclerotic cardiovascular disease because it significantly reduces cholesterol. (5) A study published in the Journal of Biomolecules indicated that trazodone inhibits DHCR7, an enzyme used in cholesterol formation, and thus reduces cholesterol levels. (6)

Another study published in the Journal of Circulation in 2018 suggested that trazodone decreased cholesterol synthesis compared to controls and could be used for atherosclerotic cardiovascular disease. (7)

What are the benefits and harmful effects of trazodone-induced low cholesterol? 

Trazodone-induced low cholesterol can be beneficial in some cases and harmful in others. To avoid any harm, it’s essential for healthcare providers to consider the effect of trazodone on cholesterol before prescribing it.

  • Benefits: Trazodone’s ability to reduce cholesterol levels by inhibiting the DHCR7 enzyme makes it useful in the treatment of atherosclerotic cardiovascular disease, hypercholesterolemia, hyperlipidemia, and obesity. (7)

 

  • Harmful effects: Trazodone-induced low cholesterol can be harmful to pregnant women because cholesterol is important for developing the brain of the fetus, so trazodone should not be prescribed in pregnancy. (8)

Hypolipidemia can cause certain side effects, including strokes, dementia, depression, hematuria, and cancers. (9)

 

What to do if trazodone affects your cholesterol levels?

If trazodone is causing a reduction in your cholesterol levels, consult your healthcare provider about the possible effects of low cholesterol. Your doctor might suggest the following:

  • Lowering the dose: If trazodone is causing a significant decrease in your cholesterol levels, your doctor might consider lowering the dose to avoid the effects associated with extremely low cholesterol.

 

  • Monitoring: If trazodone is reducing your cholesterol levels, regular monitoring of the cholesterol levels will help avoid any unwanted consequences.

 

  • Exploring alternates: If reducing the dose does not help, your doctor might consider exploring alternate antidepressants that do not cause low cholesterol.

 

  • Lifestyle modification: Taking a nutritious diet with healthy fats can help with the low cholesterol induced by trazodone.

 

  • Fat-soluble vitamins: Taking vitamins A, D, K, and E can also help with the low cholesterol induced by trazodone.

 

How to ensure the safe use of trazodone?

Ensuring the safe use of trazodone requires a collaborative effort between patients and healthcare providers. Here are a few guidelines to ensure the safe use of trazodone:

Medical history: Before starting trazodone, discuss your medical history, including any pre-existing conditions, allergies, and medications (OTC, prescription, herbal, or supplements) you are currently taking.

Follow prescription: Follow the exact dose and schedule prescribed by your healthcare provider. Do not make changes to the dose or stop taking the medication without consulting your doctor.

Regular monitoring: Schedule regular follow-up appointments with your healthcare provider to monitor the efficacy of trazodone and assess for any side effects. Blood tests may be done to monitor cholesterol levels and liver function.

Avoid alcohol: Limit or avoid alcohol consumption while taking trazodone, as alcohol can interact with trazodone and enhance its sedative effects. 

Be cautious with other sedatives: Inform your healthcare provider if you are taking other sedatives, as taking them with trazodone may exacerbate sedation and increase the risk of adverse effects.

Report side effects: Be on the lookout for any potential side effects of trazodone, such as dizziness, headache, nausea, bruising, prolonged QTc, etc. Report these side effects immediately to your healthcare provider for appropriate management.

Gradual discontinuation: If your healthcare provider decides to discontinue trazodone, they will recommend a gradual tapering to minimize withdrawal symptoms. 

Emergency situations: In cases of severe side effects, allergic reactions, or overdose symptoms (such as difficulty breathing or loss of consciousness), seek emergency medical attention immediately.

 

According to my knowledge, the relationship between trazodone and cholesterol remains a subject of ongoing research and discussion. Patients taking trazodone should communicate with their healthcare providers about any concerns regarding cholesterol levels.

The decision to prescribe or discontinue trazodone should be based on careful consideration of the individual’s overall health and the potential benefits of the medication in managing mental health conditions.

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References

1.-

Shin JJ, Saadabadi A. Trazodone. [Updated 2022 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470560/

2.-

Huff T, Boyd B, Jialal I. Physiology, Cholesterol. [Updated 2023 Mar 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470561/

3.-

Hitoshi Watanabe, Daisuke Akasaka, Hideki Ogasawara, Kan Sato, Masato Miyake, Kazuki Saito, Yu Takahashi, Takashi Kanaya, Ikuro Takakura, Tetsuya Hondo, Guozheng Chao, Michael T. Rose, Shyuichi Ohwada, Kouichi Watanabe, Takahiro Yamaguchi, Hisashi Aso, Peripheral Serotonin Enhances Lipid Metabolism by Accelerating Bile Acid Turnover, Endocrinology, Volume 151, Issue 10, 1 October 2010, Pages 4776–4786, https://doi.org/10.1210/en.2009-1349

4.-

Perry PJ, Garvey MJ, Dunner DL, Rush AJ, Kyhl J. A report of trazodone-associated laboratory abnormalities. Ther Drug Monit. 1990 Nov;12(6):517-9. doi: 10.1097/00007691-199011000-00001. PMID: 2274996. https://pubmed.ncbi.nlm.nih.gov/2274996/#:~:text=The%20hematocrit%2C%20hemoglobin%2C%20red%20blood,for%20the%20fluoxetine%20treatment%20group.

5.-

Kipp Johnson, Jagat Narula, Benjamin Glicksberg et al. Repurposing the atypical antidepressant trazodone for atherosclerotic cardiovascular disease, 29 June 2021, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-567817/v1

6.-

Korade, Z., Anderson, A., Balog, M., Tallman, K. A., Porter, N. A., & Mirnics, K. (2023). Chronic Aripiprazole and Trazodone Polypharmacy Effects on Systemic and Brain Cholesterol Biosynthesis. Biomolecules, 13(9). https://doi.org/10.3390/biom13091321

7.-

Translational Systems Genetics, Electronic Medical Record Analysis, and Molecular Imaging Reveal That the Antidepressant Trazodone Reduces Atherosclerosis as Well as Statins: Drug Discovery by Repurposing of Proven Safe Drugs
Kipp W Johnson, Jagat Narula, Benjamin S Glicksberg, Khader Shameer, Farhan Chaudhry, Alexandre Yahi, Ben Readhead, Nayaab S Khan, Letizia Amadori, Christine Becker, Aparna A Divaraniya, Milo R Smith, Li Li, Yuliya Vengrenyuk, Benjamin McCauley, Deepak Kaji, David Stark, Koon Yan Pak, Brian Gray, Usman Baber, Nick Tatonetti, Atul J Butte, Artiom Petrov, Navneet Narula, Chiara Giannarelli, Samin K Sharma, Joel T Dudley and Annapoorna S Kini
Originally published5 Nov 2018Circulation. 2018;138:A10647 https://www.ahajournals.org/doi/10.1161/circ.138.suppl_1.10647

8.-

Korade Z, Heffer M, Mirnics K. Medication effects on developmental sterol biosynthesis. Mol Psychiatry. 2022 Jan;27(1):490-501. doi: 10.1038/s41380-021-01074-5. Epub 2021 Apr 5. PMID: 33820938; PMCID: PMC8490477. https://pubmed.ncbi.nlm.nih.gov/33820938/

9.-

Bandyopadhyay, D., Qureshi, A., Ghosh, S., Ashish, K., Heise, L. R., Hajra, A., & Ghosh, R. K. (2018). Safety and Efficacy of Extremely Low LDL-Cholesterol Levels and Its Prospects in Hyperlipidemia Management. Journal of Lipids, 2018. https://doi.org/10.1155/2018/8598054

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