Table 1.
Studies investigating the associations between statin use and depression.
| References | Study design | Subjects number (mean age) | F/U duration | Assessment | Diagnosis | Statin name and dosage | Main findings |
|---|---|---|---|---|---|---|---|
| EPIDEMIOLOGICAL STUDY | |||||||
| Young-Xu et al. (54) | Prospective | 606 CAD patients (67 yrs) | 4–7 years | Kellner Symptom Questionnaire | Psychological well-being | Any use | Reduced risk of abnormal depression scores in CAD patients: aOR (95% CI) = 0.63 (0.43–0.93) |
| Stafford et al. (52) | Prospective | 193 heart disease patients (64 yrs) | 9 months | 3M-MINI 9M-HADS | Major and minor depression dysthymia | Atorvastain, Pravastatin, Simvastatin | Reduced risk of dysthymia, minor depression, or major depression both at 3 and 9 months 3 mo: aOR (95% CI) = 0.31 (0.10–0.97) 9 mo: aOR (95% CI) = 0.21 (0.05–0.88) |
| Otte et al. (55) | Prospective | 965 CAD patients (67 ± 11 yrs) |
6 years | PHQ | PHQ ≥10 depression | Any use | Reduced risk of depression aOR (95% CI) = 0.62 (0.41–0.95) |
| Yang et al. (56) | Retrospective | 458 depression and 1,830 controls (55 ± 9 yrs) | NA | Recorded diagnosis of depression | Depression Suicidal behavior | Any use | Reduced risk of depression aOR (95% CI) = 0.4 (0.2–0.9) |
| Pasco et al. (57) | Retrospective | 22 Women with MDD and 323 Control (72 ± 9 yrs) | 10 years | SCID using DSM-IV | MDD | Not reported | Reduced risk for MDD. Hazard ratio [HR] (95% CI) = 0.20 (0.04–0.85) |
| Al Badarin et al. (58) | Prospective | 3,050 statin user and 625 statin nonuser (58 ± 12 yrs) | 1 year | PHQ-8 | PHQ-8≥10 depression | NA | No significant association in myocardial infarction patients |
| Redlich et al. (59) | Retrospective | 4,607,990 National register data (63 ± 17 yrs) | 2 years | ICD-10 codes F30–F39 | Depressive disorder | Any use | Lipophilic agents- reduction in risk aOR(95% CI) = 0.92 (0.88–0.96) Hydrophilic agents-no association aOR(95% CI) = 0.85 (0.70–1.03) |
| Chuang et al. (60) | Retrospective (health insurance) | 26,852 hyperlipidemia patients (52 ± 14 yrs) | NA | Insurance claim | Depressive disorder | NA | Reduced risk of depression in hyperlipidemia patients; HR (95% CI) = 0.81 (0.69–0.96) |
| Kim et al. (61) | Prospective | 423 stroke patients (65 ± 10 yrs) |
1 year | MINI (DSM-IV) HDRS | Major or minor depression | Any use | Reduced risk of depression in stroke patients; aOR (95% CI) = 0.54 (0.49–0.87) |
| Kang et al. (62) | Retrospective (health insurance) | 11,218 stroke patients (71 ± 12 yrs) |
1 year | ICD-9-CM 296.2, 296.3, 300.4, or 311 | Depression | NA | Increased risk of depressive disorder following stroke: aHR(95% CI) = 1.65 (1.34–2.03) |
| Glaus et al. (63) | Prospective cohort | 1,631 community population (52 ± 9 yrs) | 5.2 ± 1.2 years | DIGS | DSM-IV MDD | NA | No association of MDD risk aHR(95% CI) = 1.25(0.73–2.14) |
| Kohler et al. (64) | Prospective (Danish Civil Registration) | 872,216 SSRI users (48 [33-68] yrs) | 3 years | ICD-10 F32 or F33; suicide attempt | NA | Any use | Adjunctive stain use with SSRI -Reduced risk for psychiatric hospital contacts due to depression: aHR(95% CI) = 0.64 (0.55–0.75) |
| INTERVENTIONAL STUDY | |||||||
| Ghanizadeh et al. (65) | DB RCT | 68 statin use and placebo (32 ± 10 yrs) | 6 weeks | HDRS | DSM-IV MDD, (HDRS > 17) | Fluoxetine up to 40 mg/d + Lovastatin 30 mg/d | “Lovastatin + fluoxetine” improved depressive symptoms HDRS reduction 12.8(6.3) vs. 8.2(4.0), P < 0.001 No adverse effect |
| Haghighi et al. (66) | DB RCT | 60 statin use and Placebo (32 ± 8 yrs) | 12 weeks | HDRS | DSM-5 MDD, (HDRS ≥ 25) | Citalopram 40 mg/d + Atorvastatin 20 mg/d | “Atorvastatin + SSRI” improved depressive symptoms Partial remission OR 8.83(1.02–76.96): Statin user vs. non-user |
| Gougol et al. (67) | DB RCT | 48 statin use and Placebo (35 ± 10 yrs) | 6 weeks | HDRS | DSM-IV MDD, (HDRS > 17) | Fluoxetine 40 mg/d + Simvastatin 20 mg/d | “Simvastatin + fluoxetine” improved depressive symptoms No adverse effect |
| Abbasi et al. (68) | DB RCT | 46 patients received CABG (57 ± 7 yrs) |
6 weeks | HDRS | DSM-IV MDD, (HDRS ≥ 19) | Simvastatin 20 mg/d Atorvastatin 20 mg/d |
Earlier and superior effect of improving depressive symptoms; simvastatin > atorvastatin No serious adverse effect |
| Kim et al. (7) | Naturalistic prospective observation study | 446 patients with CAD (59 ± 11 yrs) |
24 weeks & 1 year | HDRS, BDI | MINI: MDD or minor depressive Dis |
Any use lipophilic vs. hydrophilic statins |
Improved depressive symptoms and response rate: Escitalopram + statin > statin > escitalopram > none Response rate: lipophilic statins > hydrophilic statins, OR (95% CI) 3.91 (1.21–12.59) |
yrs, years; aOR, Adjusted odd ratio; CAD, coronary artery disease; MINI, Mini International Neuropsychiatric Interview; HADS, Hospital Anxiety and Depression Scale; PHQ, Patients Health Questionnaire; NA, not assessed; MDD, major depressive disorder; Dis, disorder; SCID, Structured Clinical Interview for DSM; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders 4th edition; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; ICD-10, International Classification of Diseases 10th revision; HDRS, Hamilton Depression Rating Scale; DIGS, Diagnostic Interview for Genetic Studies; DSM-5, Diagnostic and Statistical Manual of Mental Disorders 5th edition; BDI, Beck Depression Inventory.