The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Study Population
Assessment of Statin Use
Dose and Duration of Treatment
Time at Risk and Follow-Up
Definition of Outcomes
Assessment of Covariates
Statistical Analysis
Main analyses.
Propensity-score matched analyses.
Sensitivity analyses.
Results
Characteristic | All SSRI Users (N=872,216) | Users of SSRIs Only (N=759,108) | Concomitant Users of SSRIs and Statins (N=113,108) | |||
---|---|---|---|---|---|---|
Median | IQR | Median | IQR | Median | IQR | |
Age (years) | 48.0 | 33.4, 67.8 | 45.7 | 31.6, 68.2 | 56.2 | 47.2, 66.5 |
N | % | N | % | N | % | |
Female | 536,019 | 61.6 | 469,623 | 62.0 | 66,396 | 58.7 |
Age groups (years) | ||||||
10–29 | 170,862 | 19.6 | 168,443 | 22.2 | 2,419 | 2.1 |
30–49 | 291,312 | 33.5 | 257,649 | 34.0 | 33,663 | 29.8 |
50–69 | 210,151 | 24.1 | 153,881 | 20.3 | 56,270 | 49.8 |
70–89 | 181,265 | 20.8 | 160,757 | 21.2 | 20,508 | 18.1 |
≥90 | 17,311 | 2.0 | 17,080 | 2.3 | 231 | 0.2 |
Education | ||||||
Primary school | 366,930 | 42.1 | 314,756 | 41.5 | 52,174 | 46.1 |
Secondary school | 33,570 | 3.9 | 31,871 | 4.2 | 1,699 | 1.5 |
Vocational | 1,722 | 0.2 | 1,578 | 0.2 | 144 | 0.1 |
Short higher | 204,268 | 23.5 | 171,519 | 22.6 | 32,749 | 29.0 |
Medium higher | 130,016 | 14.9 | 113,110 | 14.9 | 16,906 | 15.0 |
University | 134,395 | 15.4 | 124,976 | 16.5 | 9,419 | 8.2 |
Index year | ||||||
1997 | 64,521 | 7.4 | 51,747 | 6.8 | 12,774 | 11.3 |
1998 | 58,104 | 6.7 | 47,117 | 6.2 | 10,987 | 9.7 |
1999 | 51,369 | 5.9 | 41,793 | 5.5 | 9,576 | 8.5 |
2000 | 53,083 | 6.1 | 43,675 | 5.8 | 9,408 | 8.3 |
2001 | 60,366 | 6.9 | 49,705 | 6.6 | 10,661 | 9.4 |
2002 | 57,744 | 6.6 | 47,756 | 6.3 | 9,988 | 8.8 |
2003 | 63,743 | 7.3 | 53,479 | 7.0 | 10,264 | 9.1 |
2004 | 52,327 | 6.0 | 44,530 | 5.9 | 7,797 | 6.9 |
2005 | 56,112 | 6.4 | 48,651 | 6.4 | 7,461 | 6.6 |
2006 | 56,209 | 6.4 | 49,664 | 6.5 | 6,545 | 5.8 |
2007 | 54,772 | 6.3 | 49,145 | 6.5 | 5,627 | 5.0 |
2008 | 51,094 | 5.9 | 47,107 | 6.2 | 3,987 | 3.5 |
2009 | 54,348 | 6.2 | 51,018 | 6.7 | 3,330 | 2.9 |
2010 | 55,061 | 6.3 | 52,537 | 6.9 | 2,524 | 2.2 |
2011 | 43,324 | 5.0 | 41,887 | 5.5 | 1,437 | 1.3 |
2012 | 40,039 | 4.6 | 39,297 | 5.2 | 742 | 0.7 |
Previous mental disorders | ||||||
Any contact | 169,436 | 19.4 | 151,918 | 20.0 | 17,518 | 15.5 |
Depression | 45,746 | 5.3 | 40,806 | 5.4 | 4,940 | 4.4 |
Schizophrenia spectrum | 22,870 | 2.6 | 20,450 | 2.7 | 2,420 | 2.1 |
Bipolar disorder | 5,828 | 0.7 | 5,204 | 0.7 | 624 | 0.6 |
Anxiety | 24,188 | 2.8 | 21,563 | 2.9 | 2,625 | 2.3 |
Substance abuse | 35,239 | 4.1 | 30,636 | 4.0 | 4,603 | 4.1 |
Other mental disorders | 68,939 | 7.9 | 62,799 | 8.3 | 6,140 | 5.4 |
Previous medical diseases | ||||||
Any disorder | 210,968 | 24.2 | 180,206 | 23.8 | 30,762 | 27.2 |
Myocardial infarction | 20,724 | 2.4 | 17,119 | 2.3 | 3,605 | 3.2 |
Congestive heart failure | 13,732 | 1.6 | 12,409 | 1.6 | 1,323 | 1.2 |
Peripheral vascular disease | 19,669 | 2.3 | 16,292 | 2.2 | 3,377 | 3.0 |
Cerebrovascular disease | 21,850 | 2.5 | 18,194 | 2.4 | 3,656 | 3.2 |
Dementia | 9,870 | 1.1 | 9,433 | 1.2 | 437 | 0.4 |
Chronic pulmonary disease | 53,420 | 6.1 | 46,860 | 6.2 | 6,560 | 5.8 |
Connective tissue disease | 19,191 | 2.2 | 16,592 | 2.2 | 2,699 | 2.4 |
Ulcer disease | 28,143 | 3.2 | 23,818 | 3.1 | 4,325 | 3.8 |
Mild liver disease | 7,672 | 0.9 | 6,755 | 0.9 | 917 | 0.8 |
Diabetes | 16,492 | 1.9 | 12,048 | 1.6 | 4,444 | 3.9 |
Hemiplegia | 1,499 | 0.2 | 1,338 | 0.2 | 161 | 0.1 |
Moderate to severe renal disease | 7,643 | 0.9 | 6,625 | 0.9 | 1,018 | 0.9 |
Diabetes with end organ damage | 8,775 | 1.0 | 6,406 | 0.9 | 2,369 | 2.1 |
Any tumor | 63,169 | 7.3 | 56,441 | 7.5 | 6,728 | 6.0 |
Leukemia | 1,677 | 0.2 | 1,543 | 0.2 | 134 | 0.1 |
Lymphoma | 3,661 | 0.4 | 3,316 | 0.4 | 345 | 0.3 |
Liver disease | 722 | 0.1 | 647 | 0.1 | 75 | 0.1 |
Metastatic solid tumor | 6,977 | 0.8 | 6,685 | 0.9 | 292 | 0.3 |
AIDS | 897 | 0.1 | 784 | 0.1 | 113 | 0.1 |
Previous cardiovascular drug use | ||||||
Any use | 263,535 | 30.2 | 217,183 | 28.6 | 46,352 | 41.0 |
Diuretics | 150,993 | 17.9 | 126,743 | 17.4 | 24,250 | 21.5 |
Renin-angiotensin system drugs | 85,517 | 10.1 | 67,389 | 9.2 | 18,128 | 16.1 |
Beta-blockers | 78,850 | 9.4 | 63,108 | 8.6 | 15,742 | 14.0 |
Calcium channel blockers | 65,827 | 7.8 | 52,610 | 7.2 | 13,217 | 11.7 |
Vasoprotective agents | 40,773 | 4.8 | 35,102 | 4.8 | 5,671 | 5.0 |
Antihypertensives | 4,524 | 0.5 | 3,610 | 0.5 | 914 | 0.8 |
Other lipid-modifying agents | 1,807 | 0.2 | 1,434 | 0.2 | 373 | 0.3 |
Peripheral vasodilators | 263 | <0.1 | 214 | <0.1 | 49 | 0.04 |
Previous anti-inflammatory drug use | ||||||
Any use | 749,141 | 85.9 | 643,769 | 84.8 | 105,372 | 93.2 |
Corticosteroids | 265,885 | 31.5 | 219,032 | 30.0 | 46,853 | 41.5 |
Antirheumatics | 259 | <0.1 | 211 | <0.1 | 48 | 0.04 |
NSAIDs | 708,611 | 84.1 | 607,206 | 83.2 | 101,405 | 89.9 |
Low-dose aspirin | 92,814 | 11.0 | 78,529 | 10.8 | 14,285 | 12.7 |
Previous psychopharmaceutical use | ||||||
Any use | 591,443 | 67.8 | 502,086 | 66.1 | 89,357 | 79.0 |
Antidepressants other than SSRIs | 80,583 | 9.6 | 68,686 | 9.4 | 11,897 | 10.5 |
Antipsychotics | 67,238 | 8.0 | 59,069 | 8.1 | 8,169 | 7.2 |
Lithium | 2,853 | 0.3 | 2,512 | 0.3 | 341 | 0.3 |
Other mood stabilizers | 64,471 | 7.7 | 54,225 | 7.4 | 10,246 | 9.1 |
Anxiolytics | 466,321 | 55.3 | 391,949 | 53.7 | 74,372 | 65.9 |
Benzodiazepine-like hypnotics | 297,208 | 35.3 | 249,463 | 34.2 | 47,745 | 42.3 |
Effects on Psychiatric Hospital Contacts
Outcome and Medication Group | Nb (events) | Person-Years | Crude Hazard Ratioc | 95% CI | Adjusted Hazard Ratiod | 95% CI |
---|---|---|---|---|---|---|
Contacts with psychiatric hospitals (any cause) | ||||||
SSRI alone | 78,023 | 514,810 | 1.0 | Ref. | 1.0 | Ref. |
SSRI plus a statin | 11,883 | 73,142 | 0.65 | 0.60, 0.71 | 0.75 | 0.69, 0.82 |
Simvastatin | 11,228 | 67,371 | 0.65 | 0.60, 0.72 | 0.76 | 0.70, 0.83 |
Other statinse | 655 | 5,771 | 0.61 | 0.45, 0.83 | 0.66 | 0.49, 0.89 |
Citalopram only | 40,202 | 268,368 | 1.0 | Ref. | 1.0 | Ref. |
Citalopram plus simvastatin | 5,677 | 32,856 | 0.60 | 0.53, 0.67 | 0.72 | 0.64, 0.81 |
Contacts with psychiatric hospitals due to depression | ||||||
SSRI alone | 29,231 | 521,998 | 1.0 | Ref. | 1.0 | Ref. |
SSRI plus a statin | 3,937 | 74,226 | 0.59 | 0.50, 0.68 | 0.64 | 0.55, 0.75 |
Simvastatin | 3,720 | 69,044 | 0.60 | 0.51, 0.70 | 0.66 | 0.56, 0.77 |
Other statinse | 217 | 5,182 | 0.49 | 0.28, 0.86 | 0.54 | 0.30, 0.94 |
Citalopram only | 15,178 | 290,674 | 1.0 | Ref. | 1.0 | Ref. |
Citalopram plus simvastatin | 2,028 | 33,154 | 0.58 | 0.48, 0.71 | 0.66 | 0.54, 0.80 |
All-cause mortality | ||||||
SSRI alone | 36,035 | 520,380 | 1.0 | Ref. | 1.0 | Ref. |
SSRI plus a statin | 4,040 | 73,467 | 1.00 | 0.93, 1.08 | 1.04 | 0.96, 1.12 |
Simvastatin | 3,833 | 68,818 | 1.00 | 0.92, 1.07 | 1.02 | 0.95, 1.10 |
Other statinse | 207 | 4,649 | 0.99 | 0.89, 1.51 | 1.24 | 0.95, 1.62 |
Citalopram only | 25,911 | 303,712 | 1.0 | Ref. | 1.0 | Ref. |
Citalopram plus simvastatin | 2,065 | 30,981 | 0.98 | 0.90, 1.06 | 1.02 | 0.94, 1.11 |
Suicidal behavior | ||||||
SSRI alone | 6,746 | 528,374 | 1.0 | Ref. | 1.0 | Ref. |
SSRI plus a statin | 469 | 74,189 | 0.79 | 0.56, 1.10 | 0.85 | 0.61, 1.18 |
Simvastatin | 426 | 68,395 | 0.79 | 0.56, 1.12 | 0.85 | 0.60, 1.20 |
Other statinse | 43 | 5,794 | 0.74 | 0.24, 2.31 | 0.81 | 0.26, 2.52 |
Citalopram only | 3,350 | 226,355 | 1.0 | Ref. | 1.0 | Ref. |
Citalopram plus simvastatin | 321 | 30,251 | 0.62 | 0.39, 0.99 | 0.65 | 0.41, 1.04 |
Adverse Events
Propensity-Score Matched Analyses
Sensitivity Analyses
Discussion
Supplementary Material
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