Statin Use and Risk of Depression

Table 1. Individual characteristics, number of depression cases by independent variable, and age-standardized rates (p/1000 population) for diagnosis of depression between 2006–2008 ( n = 4,607,990)
	Population	% of total population	Number of cases	Rate	95% CI
Age
40–49	1,238,099	26.9	5,607	4.53	4.38–4.62
50–59	1,190,481	25.8	5,048	4.24	4.08–4.32
60–69	1,033,816	22.4	3,886	3.76	3.68–3.92
70+	1,145,594	24.9	5,751	5.02	4.87–5.13
Gender
Male	2,220,494	48.19	8,317	3.75	3.67–3.83
Female	2,387,496	51.81	11,975	4.99	4.90–5.08
Civil status
Married/cohabitating	2,498,864	54.23	7,456	3.05	2.98–3.12
Unmarried/widowed/divorced/single	2,109,126	45.77	12,836	6.09	5.98–6.20
Immigration
Born in Sweden	3,968,191	86.12	17,298	4.36	4.30–4.42
Born elsewhere	639,799	13.88	2,994	4.63	4.46–4.80
Education
Compulsory school or less (≤ 9yrs)	1,244,872	27.02	6,384	5.03	4.91–5.15
Practical high school or some theoretical high school (10–11yrs)	1,243,067	26.98	5,841	4.76	4.64–4.88
Theoretical high school and/or college (≥ 12yrs)	2,120,051	46.01	8,067	3.93	3.84–4.02
Income
Low income	1,018,845	22.11	5,161	5.08	4.94–5.22
Middle low income	1,219,372	26.46	7,421	6.15	6.01–6.29
Middle high income	1,151,642	24.99	4,589	3.99	3.87–4.11
High income	1,218,131	26.44	3,121	2.79	2.69–2.89
Hospitalisation for COPD
No	4,581,872	99.43	19,908	4.35	4.29–4.41
Yes	26,118	0.57	384	19.86	17.87–21.85
Hospitalisation for alcohol dependence
No	4,583,249	99.46	18,856	4.12	4.06–4.18
Yes	24,741	0.54	1,436	54.34	51.53–57.15
Hospitalisation for CHD
No	4,496,433	97.6	19,599	4.37	4.31–4.43
Yes	111,557	2.4	693	7.02	6.50–7.54
Region
Large cities	2,259,664	49.04	10,452	4.64	4.55–4.73
Southern	1,579,534	34.28	6,617	4.19	4.09–4.29
Northern	768,792	16.68	3,223	4.2	4.05–4.35
Statin prescriptions
Any statin	804,832	17.47	3,313	4.59	4.43–4.75
Simvastatin	665,932	14.45	2,707	4.45	4.28–4.62
Pravastatin	27,244	0.59	103	5.21	4.20–6.22
Fluvastatin	5,932	0.13	24	5.07	3.04–7.10
Atorvastatin	95,231	2.07	429	5.49	4.97–6.01
Rosuvastatin	10,493	0.23	50	5.11	3.69–6.53

IR = age-standardized incidence rate; CI = confidence interval.
COPD = chronic obstructive pulmonary disease.
CHD = coronary heart disease.

Table 2. Unadjusted and adjusted ORs from logistic regression for association between statin prescription and subsequent diagnosis of depression between 2006–2008 ( n = 4,607,990)
	Unadjusted OR	95% CI	p-value	Age-adjusted OR	95% CI	p-value	Adjusted OR^a	95% CI	p-value
Statin prescriptions
Any statin	0.92	0.89–0.96	<0.001	0.92	0.88–0.95	<0.001	0.95	0.91–0.99	0.016
Simvastatin	0.91	0.87–0.95	<0.001	0.91	0.87–0.94	<0.001	0.93	0.89–0.97	0.001
Pravastatin	0.86	0.71–1.04	0.120	0.85	0.70–1.03	0.090	0.90	0.74–1.09	0.268
Fluvastatin	0.92	0.61–1.37	0.677	0.91	0.61–1.36	0.643	0.98	0.65–1.46	0.914
Atorvastatin	1.02	0.93–1.13	0.632	1.03	0.94–0.97	0.507	1.11	1.01–1.22	0.032
Rosuvastatin	1.08	0.82–1.43	0.578	1.12	0.84–1.47	0.443	1.21	0.92–1.60	0.177

CI = confidence interval; OR = odds ratio.
^aThe model includes prescription of statin medication (any statin, and by individual statins) and the following variables as covariates: gender, age (40–49, 50–59, 60–69, 70+), marital status, education (three levels), family income (quartiles), hospitalisation for cardio-pulmonary disease, hospitalisation for alcoholism, hospitalisation for coronary heart disease, and region (large cities, Southern, Northern).

Table 3. Adjusted ORs from multivariable logistic regression for association between statin prescription and subsequent diagnosis of depression between 2006–2008, by increasing age group ( n = 4,607,990)
	Age ≥40 yrs			Age ≥50 yrs			Age ≥60 yrs			Age ≥70 yrs
	OR^a	95% CI	p-value	OR^a	95% CI	p-value	OR^a	95% CI	p-value	OR^a	95% CI	p-value
Statin prescriptions
Any statin	0.95	0.91–0.99	0.016	0.91	0.87–0.95	<0.001	0.85	0.81–0.89	<0.001	0.81	0.76–0.87	<0.001
Simvastatin	0.93	0.89–0.97	0.001	0.90	0.86–0.94	<0.001	0.85	0.81–0.90	<0.001	0.82	0.76–0.87	<0.001
Pravastatin	0.90	0.74–1.09	0.268	0.84	0.69–1.04	0.104	0.80	0.64–1.01	0.061	0.72	0.54–0.96	0.026
Fluvastatin	0.98	0.65–1.46	0.914	0.91	0.59–1.39	0.660	0.89	0.55–1.43	0.662	1.03	0.60–1.78	0.906
Atorvastatin	1.11	1.01–1.22	0.032	1.04	0.94–1.16	0.427	0.95	0.84–1.07	0.384	0.93	0.80–1.10	0.412
Rosuvastatin	1.21	0.92–1.60	0.177	1.18	0.88–1.60	0.274	1.10	0.75–1.60	0.635	1.21	0.71–2.04	0.485

CI = confidence interval; OR = odds ratio.
^aThe model includes prescription of statin medication (any statin, and by individual statins) and the following variables as covariates: gender, age (40–49, 50–59, 60–69, 70+), marital status, education (three levels), family income (quartiles), hospitalisation for cardio-pulmonary disease, hospitalisation for alcoholism, hospitalisation for coronary heart disease, and region (large cities, Southern, Northern).

Authors and Disclosures

Cassie Redlich¹, Michael Berk^2,3, Lana J Williams^2,3, Jan Sundquist^1,4*, Kristina Sundquist^1,4 and Xinjun Li¹

¹Center for Primary Health Care Research, Lund University, Lund, Sweden. ²IMPACT Strategic Research Centre, School of Medicine, Deakin University, Locked Bag 20000, Geelong 3220, Australia. ³Department of Psychiatry, The University of Melbourne, Parkville, Australia. ⁴Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA

*Correspondence
jan.sundquist@med.lu.se

Competing interests
Michael Berk has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Meat and Livestock Board, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma and Servier, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck Merck and Servier.
Lana Williams has received Grant/Research support from Eli Lilly, Pfizer, The University of Melbourne, Deakin University and the NHMRC.
Cassie Redlich, Jan Sundquist, Kristina Sundquist and Xinjun Li have no conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.

Authors' contributions
CR, MB, LW, JS & XL contributed to the design of the project; CR and XL performed the statistical analysis; CR wrote the manuscript; MB, LW, JS, KS & XL contributed to the drafting and editing of the manuscript, JS and KS had final approval of the version to be published; all authors read and approved the final manuscript.