CNS Drugs

, Volume 23, Issue 10, pp 857–865 | Cite as

Effects of Paroxetine and Sertraline on Low-Density Lipoprotein Cholesterol

An Observational Cohort Study
  • Feifei Wei
  • A. Lauren Crain
  • Robin R. Whitebird
  • Olga V. Godlevsky
  • Patrick J. O’Connor
Original Research Article


Background: Antidepressant use in US adults increased 3-fold from 2.5% in 1988–94 to 8.1% in 1999–2002, based on National Health and Nutrition Examination Surveys. As the use of antidepressants increases, a comprehensive understanding of the potential health risks that may be associated with their use becomes increasingly important.

Objective: This study evaluated the effects of paroxetine and sertraline on low-density lipoprotein cholesterol (LDL-C).

Study Design: An observational cohort study (1997–2004) of adults who had taken paroxetine or sertraline for at least 60 continuous days and had ≥2 LDL-C values measured during the study period, one while taking and one while not taking paroxetine or sertraline. A total of 13 634 LDL-C values clustered within 2682 patients were studied.

Methods: We conducted mixed model regression analyses to quantify the relationship between antidepressant use and LDL-C values.

Results: The number of days taking paroxetine (β = 0.0045; 95% CI 0.0018, 0.0073) and sertraline (β = 0.0074; 95% CI 0.0054, 0.0093) prior to the LDL-C test were related to higher LDL-C values, after accounting for age, sex, year LDL-C was tested, co-morbidity, depression and lipid medication. The number of days that had passed since exposure to paroxetine (β =−0.0013; 95% CI −0.0020, −0.00061) or sertraline (β = −0.00093; 95% CI −0.016, −0.00022) were related to lower LDL-C values. The significant interaction between exposure to an antidepressant and taking a lipid medication demonstrates that the increase in LDL-C values associated with antidepressant use is ameliorated among patients who were taking a lipid medication when LDL-C was measured.

Conclusion: Our study showed that long-term use of paroxetine or sertraline may have a measurable adverse impact on cardiovascular risk in adults. Clinical strategies should be used to address cardiovascular risk while maintaining effective treatment of major depression. In light of these findings, attention to LDL-C values should accompany antidepressant use.


Cardiovascular Risk Paroxetine Sertraline Antidepressant Medication Depression Diagnosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The Health Partners Research Foundation provided funding for this study. The authors have no conflicts of interest that are directly relevant to the content of this study.


  1. 1.
    Paulose-Ram R, Safran MA, Jonas BS, et al. Trends in psychotropic medication use among US adults. Pharmacoepidemiol Drug Saf 2007; 16(5): 560–70PubMedCrossRefGoogle Scholar
  2. 2.
    Larson M, Miller K, Fleming K. Treatment with antidepressant medications in private health plans. Admin Policy Mental Health Mental Health Serv Res 2007; 34(2): 116–26CrossRefGoogle Scholar
  3. 3.
    Wolfe GI, Trivedi JR. Painful peripheral neuropathy and its nonsurgical treatment. Muscle Nerve 2004 Jul; 30(1): 3–19PubMedCrossRefGoogle Scholar
  4. 4.
    Backonja MM, Serra J. Pharmacologic management part 1: better-studied neuropathic pain diseases. Pain Med 2004 Mar; 5Suppl. 1: S28–47PubMedCrossRefGoogle Scholar
  5. 5.
    Watson CP. The treatment of neuropathic pain: antidepressants and opioids. Clin J Pain 2000 Jun; 16(2 Suppl.): S49–55PubMedCrossRefGoogle Scholar
  6. 6.
    Krystal AD. Depression and insomnia in women. Clin Cornerstone 2004; 6Suppl. 1B: S19–28PubMedCrossRefGoogle Scholar
  7. 7.
    Institute for Clinical Systems Improvement (ICSI). Health care guideline: major depression in adults for mental health care. Bloomington (MN): Institute for Clinical Systems Improvement, 2004 MayGoogle Scholar
  8. 8.
    National Heart, Lung, and Blood Institute Working Group on Insomnia. Insomnia: assessment and management in primary care. Am Fam Physician 1999 Jun; 59(11): 3029–38Google Scholar
  9. 9.
    Lara N, Baker GB, Archer SL, et al. Increased cholesterol levels during paroxetine administration in healthy men. J Clin Psychiatry 2003 Dec; 64(12): 1455–9PubMedCrossRefGoogle Scholar
  10. 10.
    Liebowitz MR, Mangano RM. Venlafaxine XR in generalized social anxiety disorder. 42nd Annual New Clinical Drug Evaluation Unit Meeting; 2002 Jun 10–13; Boca Raton (FL)Google Scholar
  11. 11.
    Davis R, Wilde MI. Mirtazapine: a review of its pharmacology and therapeutic potential in the management of major depression. CNS Drugs 1996; 5: 389–402CrossRefGoogle Scholar
  12. 12.
    Nicholas LM, Ford AL, Esposito SM, et al. The effects of mirtazapine on plasma lipid profiles in healthy subjects. J Clin Psychiatry 2003 Aug; 64(8): 883–9PubMedCrossRefGoogle Scholar
  13. 13.
    Prozac [package insert]. Indianapolis (IN): Eli Lilly and Company, 2001Google Scholar
  14. 14.
    Remeron [package insert]. West Orange (NJ): CIMA Labs Inc., 2002Google Scholar
  15. 15.
    Serzone [package insert]. Princeton (NJ): Bristol-Myers Squibb Company, 2002Google Scholar
  16. 16.
    Lexapro [package insert]. St Louis (MO): Forest Pharmaceuticals, Inc., 2004Google Scholar
  17. 17.
    Zoloft [package insert]. New York: Roerig a Division of Pfizer Inc., 2004Google Scholar
  18. 18.
    Effexor [package insert]. Philadelphia (PA): Wyeth Pharmaceuticals, Inc., 2004Google Scholar
  19. 19.
    National Institutes of Health. NIH halts use of COX-2 inhibitor in large cancer prevention trial [media release]. 2004 Dec 17 [online]. Available from URL: [Accessed 2009 Aug 19]
  20. 20.
    Takkouche B, Montes-Martínez A, Gill SS, et al. Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf 2007; 30(2): 171–84PubMedCrossRefGoogle Scholar
  21. 21.
    Landi F, Onder G, Cesari M, et al. Psychotropic medications and risk for falls among community-dwelling frail older people: an observational study. J Gerontol A Biol Sci Med Sci 2005 May 1; 60(5): 622–6PubMedCrossRefGoogle Scholar
  22. 22.
    Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 2007 Jun 25; 167(12): 1240–5PubMedCrossRefGoogle Scholar
  23. 23.
    Haney EM, Chan BKS, Diem SJ, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 2007 Jun 25; 167(12): 1246–51PubMedCrossRefGoogle Scholar
  24. 24.
    Kim EJ, Yu BH. Increased cholesterol levels after paroxetine treatment in patients with panic disorder. J Clin Psychopharmacol 2005 Dec; 25(6): 597–9PubMedCrossRefGoogle Scholar
  25. 25.
    Institute for Clinical Systems Improvement. Health care guideline: preventive services for adults. 9th ed. Bloomington (MN): Institute for Clinical Systems Improvement, 2003Google Scholar
  26. 26.
    Institute for Clinical Systems Improvement. Health care guideline: lipid screening in adults. 8th ed. Bloomington (MN): Institute for Clinical Systems Improvement, 2004Google Scholar
  27. 27.
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972 Jun; 18(6): 499–502PubMedGoogle Scholar
  28. 28.
    National Center for Health Statistics. International classification of disease. 9th revision, clinical modification [online]. Available from URL [Accessed 2009 Jul 10]
  29. 29.
    Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992 Jun; 45(6): 613–9PubMedCrossRefGoogle Scholar
  30. 30.
    Rush WA, O’Connor PJ, Goodman MJ. Validation of a modified Charlson score for using health plan claims data. Minnesota Health Services Research Conference; 2000 Feb 22; Minneapolis (MN)Google Scholar
  31. 31.
    Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356 222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986 Nov 28; 256(20): 2823–8PubMedCrossRefGoogle Scholar
  32. 32.
    Paxil [package insert]. Research Triangle Park (NC): GlaxoSmithKline, 2004Google Scholar
  33. 33.
    Rickels K, Mangano R, Khan A. A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder. J Clin Psychopharmacol 2004 Oct; 24(5): 488–96PubMedCrossRefGoogle Scholar
  34. 34.
    Liebowitz MR, Mangano RM, Bradwejn J, et al. A randomized controlled trial of venlafaxine extended release in generalized social anxiety disorder. J Clin Psychiatry 2005 Feb; 66(2): 238–47PubMedCrossRefGoogle Scholar
  35. 35.
    Wilson PW, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation 1998 May 12; 97(18): 1837–47PubMedCrossRefGoogle Scholar
  36. 36.
    The Lipid Research Clinics Coronary Primary Prevention Trial results I: reduction in incidence of coronary heart disease. JAMA 1984 Jan 20; 251 (3): 351-64Google Scholar
  37. 37.
    The Lipid Research Clinics Coronary Primary Prevention Trial results II: the relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984 Jan 20; 251 (3): 365-74Google Scholar
  38. 38.
    Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994 Feb 5; 308(6925): 367–72PubMedCrossRefGoogle Scholar
  39. 39.
    Law MR. Lowering heart disease risk with cholesterol reduction: evidence from observational studies and clinical trials. Eur Heart J 1999; 1Suppl. S: S3–8Google Scholar
  40. 40.
    Jungkun G, Kuss HJ, Gsell W. Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans. J Neural Transm 2001; 108(3): 349–62PubMedCrossRefGoogle Scholar
  41. 41.
    Grunder G, Wetzel H, Schlosser R, et al. Subchronic antidepressant treatment with venlafaxine or imipramine and effects on blood pressure and heart rate: assessment by automatic 24-hour monitoring. Pharmacopsychiatry 1996 Mar; 29(2): 72–8PubMedCrossRefGoogle Scholar
  42. 42.
    Fava M. Weight gain and antidepressants. J Clin Psychiatry 2000; 61 Suppl. 11: 37–41Google Scholar
  43. 43.
    Ricca V, Mannucci E, Di Bernardo M, et al. Sertraline enhances the effects of cognitive-behavioral treatment on weight reduction of obese patients. J Endocrinol Invest 1996 Dec; 19(11): 727–33PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  • Feifei Wei
    • 1
  • A. Lauren Crain
    • 1
  • Robin R. Whitebird
    • 1
  • Olga V. Godlevsky
    • 1
  • Patrick J. O’Connor
    • 1
  1. 1.Health Partners Research FoundationMinneapolisUSA

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