Statin use and risk of depression: a Swedish national cohort study

BMC Psychiatry

Xinjun Li²  Kristina Sundquist³  Jan Sundquist³  Lana J Williams¹  Michael Berk¹  Cassie Redlich² 

[1]Department of Psychiatry, The University of Melbourne, Parkville, Australia

[2]Center for Primary Health Care Research, Lund University, Lund, Sweden

[3]Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA

关键词: Oxidative stress;    Inflammation;    Aetiology;    Depression;    Simvastatin;    Atorvastatin;    Statins;   

Others  :  1091573
DOI  :  10.1186/s12888-014-0348-y

 received in 2013-11-21, accepted in 2014-11-20,  发布年份 2014

【 摘 要 】

Background

Statin medications, used to prevent heart disease by reducing cholesterol, also reduce inflammation and protect against oxidative damage. As inflammation and oxidative stress occur in depression, there is interest in their potential to reduce depression risk. We investigated whether use of statin medications was associated with a change in the risk of developing depression in a very large Swedish national cohort (n = 4,607,990).

Methods

National register data for adults ≥40yr was analyzed to obtain information about depression diagnoses and prescriptions of statin medications between 2006 and 2008. Associations were tested using logistic regression.

Results

Use of any statin was shown to reduce the odds of depression by 8% compared to individuals not using statin medications (OR = 0.92, 95% CI, 0.89-0.96; p < 0.001). Simvastatin had a protective effect (OR = 0.93, 95% CI, 0.89-0.97; p = 0.001), whereas atorvastatin was associated with increased risk of depression (OR = 1.11, 95% CI, 1.01-1.22; p = 0.032). There was a stepwise decrease in odds ratio with increasing age (OR ≥ 40 years = 0.95, OR ≥ 50 years = 0.91, OR ≥ 60 years = 0.85, OR ≥ 70 years = 0.81).

Conclusions

The use of any statin was associated with a reduction in risk of depression in individuals over the age of 40. Clarification of the strength of these protective effects, the clinical relevance of these effects and determination of which statins are most effective is needed.

【 授权许可】

   
2014 Redlich et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Risk Factors in Depression. 1st edition. Elsevier, San Diego; 2008.
• [2]Organization WH: The Global Burden of Disease: 2004 update. World Health Organization, Geneva; 2008.
• [3]Andrews G, Poulton R, Skoog I: Lifetime risk of depression: restricted to a minority or waiting for most? Br J Psychiatry 2005, 187:495-496.
• [4]Maes M, Galecki P, Chang YS, Berk M: A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011, 35(3):676-692.
• [5]O’Neil A, Sanna L, Redlich C, Sanderson K, Jacka F, Williams LJ, Pasco JA, Berk M: The impact of statins on psychological wellbeing: a systematic review and meta-analysis. BMC Med 2012, 10:154. BioMed Central Full Text
• [6]Maes M, Leonard B, Fernandez A, Kubera M, Nowak G, Veerhuis R, Gardner A, Ruckoanich P, Geffard M, Altamura C, Galeki P, Berk M: (Neuro)inflammation and neuroprogression as new pathways and drug targets in depression: from antioxidants to kinase inhibitors. Prog Neuropsychopharmacol Biol Psychiatry 2011, 35(3):659-663.
• [7]Dutcher JP, Logan T, Gordon M, Sosman J, Weiss G, Margolin K, Plasse T, Mier J, Lotze M, Clark J, Atkins M: Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: a cytokine working group study. Clin Cancer Res 2000, 6(9):3442-3450.
• [8]Dell’Osso L, Pini S, Maggi L, Rucci P, Del Debbio A, Carlini M, Baldini A, Ferrari G, Manca E, Beverini E, Amore M, Scarallo V, Semeraro Q, Brunetto M, Bonino F, Maj M: Subthreshold mania as predictor of depression during interferon treatment in HCV+ patients without current or lifetime psychiatric disorders. J Psychosom Res 2007, 62(3):349-355.
• [9]Pasco JA, Jacka FN, Williams LJ, Henry MJ, Nicholson GC, Kotowicz MA, Berk M: Clinical implications of the cytokine hypothesis of depression: the association between use of statins and aspirin and the risk of major depression. Psychother Psychosom 2010, 79(5):323-325.
• [10]van der Most PJ, Dolga AM, Nijholt IM, Luiten PG, Eisel UL: Statins: mechanisms of neuroprotection. Prog Neurobiol 2009, 88(1):64-75.
• [11]Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA: Statins and the risk of dementia. Lancet 2000, 356(9242):1627-1631.
• [12]Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G: Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000, 57(10):1439-1443.
• [13]Wang Q, Yan J, Chen X, Li J, Yang Y, Weng J, Deng C, Yenari MA: Statins: multiple neuroprotective mechanisms in neurodegenerative diseases. Exp Neurol 2011, 230(1):27-34.
• [14]Tuccori M, Montagnani S, Mantarro S, Capogrosso-Sansone A, Ruggiero E, Saporiti A, Antonioli L, Fornai M, Blandizzi C: Neuropsychiatric adverse events associated with statins: epidemiology, pathophysiology, prevention and management. CNS Drugs 2014, 28(3):249-272.
• [15]Guasti L, Marino F, Cosentino M, Maio RC, Rasini E, Ferrari M, Castiglioni L, Klersy C, Gaudio G, Grandi AM, Lecchini S, Venco A: Prolonged statin-associated reduction in neutrophil reactive oxygen species and angiotensin II type 1 receptor expression: 1-year follow-up. Eur Heart J 2008, 29(9):1118-1126.
• [16]Murrow JR, Sher S, Ali S, Uphoff I, Patel R, Porkert M, Le NA, Jones D, Quyyumi AA: The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. J Clin Lipidol 2012, 6(1):42-49.
• [17]Young-Xu Y, Chan KA, Liao JK, Ravid S, Blatt CM: Long-term statin use and psychological well-being. J Am Coll Cardiol 2003, 42(4):690-697.
• [18]Hyyppa MT, Kronholm E, Virtanen A, Leino A, Jula A: Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial. Psychoneuroendocrinology 2003, 28(2):181-194.
• [19]Morales K, Wittink M, Datto C, DiFilippo S, Cary M, TenHave T, Katz IR: Simvastatin causes changes in affective processes in elderly volunteers. J Am Geriatr Soc 2006, 54(1):70-76.
• [20]Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck SB: Effects of lovastatin on cognitive function and psychological well-being. Am J Med 2000, 108(7):538-546.
• [21]Stewart RA, Sharples KJ, North FM, Menkes DB, Baker J, Simes J: Long-term assessment of psychological well-being in a randomized placebo-controlled trial of cholesterol reduction with pravastatin: The LIPID Study Investigators. Arch Intern Med 2000, 160(20):3144-3152.
• [22]Wardle J, Armitage J, Collins R, Wallendszus K, Keech A, Lawson A: Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration: Oxford Cholesterol Study Group. BMJ 1996, 313(7049):75-78.
• [23]Asplund K, Eriksson M: Inflammation, poststroke depression and statins. Int J Stroke 2011, 6(6):567-568.
• [24]Stafford L, Berk M: The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiatry 2011, 72(9):1229-1235.
• [25]Feng L, Tan CH, Merchant RA, Ng TP: Association between depressive symptoms and use of HMG-CoA reductase inhibitors (statins), corticosteroids and histamine H(2) receptor antagonists in community-dwelling older persons: cross-sectional analysis of a population-based cohort. Drugs Aging 2008, 25(9):795-805.
• [26]Yang CC, Jick SS, Jick H: Lipid-lowering drugs and the risk of depression and suicidal behavior. Arch Intern Med 2003, 163(16):1926-1932.
• [27]Otte C, Zhao S, Whooley MA: Statin use and risk of depression in patients with coronary heart disease: longitudinal data from the Heart and Soul Study. J Clin Psychiatry 2012, 73(5):610-615.
• [28]Johansson R, Carlbring P, Heedman A, Paxling B, Andersson G: Depression, anxiety and their comorbidity in the Swedish general population: point prevalence and the effect on health-related quality of life. PeerJ 2013, 1:e98.
• [29]Feng L, Yap KB, Kua EH, Ng TP: Statin use and depressive symptoms in a prospective study of community-living older persons. Pharmacoepidemiol Drug Saf 2010, 19(9):942-948.
• [30]Gengo F, Cwudzinski D, Kinkel P, Block G, Stauffer L, Lines C: Effects of treatment with lovastatin and pravastatin on daytime cognitive performance. Clin Cardiol 1995, 18(4):209-214.
• [31]While A, Keen L: The effects of statins on mood: a review of the literature. Eur J Cardiovasc Nurs 2012, 11(1):85-96.
• [32]Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Yoon JS: Vascular risk factors and incident late-life depression in a Korean population. Br J Psychiatry 2006, 189:26-30.
• [33]Kim JM, Stewart R, Kang HJ, Bae KY, Kim SW, Shin IS, Kim JT, Park MS, Cho KH, Yoon JS: A prospective study of statin use and poststroke depression. J Clin Psychopharmacol 2014, 34(1):72-79.