Table 1.
Overview of studies regarding the effects of statins on depression diagnosis in non-depressed participants.
| Publication | Study design | Population | Exposure | Comparison | Follow-up | Primary outcomes | Major Findings* | Association |
|---|---|---|---|---|---|---|---|---|
| Meta-analysis | ||||||||
| Lee et al. (72) | Meta-analysis | 13 observational studies, 5,035,070 participants | Statin use | No use | NR | Diagnosis of depression | OR = 0.87 95% CI = 0.74 to 1.02 P = NR | = |
| Parsaik et al. (73) | Meta-analysis | 7 observational studies, 9,187 participants | Statin use | No use | 5 years | Diagnosis of depression | OR = 0.68 95% CI = 0.52–0.89 P = 0.01 | + |
| Cohort studies | ||||||||
| Asplund and Eriksson (74) | Cohort | 70,706? ischemic stroke patients | Discharge on statin | No prescription | 3 months | Diagnosis of post-stroke depression or antidepressant prescription (self-reported) | OR = 0.99 95% CI = 0.95–1.03 P = NR | = |
| Chuang et al. (75) | Historical cohort | 26,852 hyperlipidaemic patients | Statin use | No use | 4 years | Diagnosis of depression | HR = 0.81 95% CI = 0.69–0.96 P < 0.05 | + |
| Dave et al. (76) | Historical cohort | 299,298 statin users | Lipophilic statin use (atorvastatin, lovastatin, simvastatin) | Hydrophilic statin use (pravastatin, rosuvastatin) | 3 years | Diagnosis of depression | Lipophilic vs. hydrophilic statins: HR = 1.05 95% CI = 1.00–1.10 P = 0.078 Simvastatin vs. hydrophilic statins: HR = 1.09 95% CI = 1.02–1.16 P = 0.003 | = / - |
| Glaus et al. (77) | Cohort | 1,631 adults aged 35–66 years | Statin use (self-reported) | No use | 5.2 years | Diagnosis of depression | HR = 1.25 95% CI = 0.73–2.14 P > 0.05 | = |
| Huang et al. (78) | Cohort | 408 HNC hyperlipidaemic patients | Statin use | No use | 1 year | Diagnosis of depression | HR = 0.85 95% CI = 0.46–1.57 P = 0.4252 | = |
| Kang et al (79) | Cohort | 286 ischemic stroke patients | Statin use | No use | 1 year | Diagnosis of post-stroke depression | Wald = 8.477 95% CI = NR P = 0.004 | + |
| Kang et al. (80) | Cohort | 11,218 ischemic stroke patients | Statin use | No use | 1 year | Diagnosis of post-stroke depression | HR = 1.59 95% CI = 1.30–1.95 P < 0.001 | - |
| Kessing et al. (81) | Historical cohort | 497,080 statin users | Statin use | No use | Up to 21 years | Diagnosis of depression or antidepressant prescription | Trend test for statin prescription = 0.92 95% CI = 0.92–0.95 P < 0.001 | + |
| Kim et al. (42) | Cohort | 711 ACS patients | Statin use | No use | 1 year | Diagnosis of depression | Prevalence difference = −9.5% (statin users) 95% CI = NR P = 0.037 | + |
| Kim et al. (82) | Cohort | 288 ischemic stroke patients | Statin use | No use | 1 year | Diagnosis of post-stroke depression | OR = 0.54 95% CI = 0.49–0.87 P = NR | + |
| Khokhar et al. (83) | Historical cohort | 100,515 TBI patients aged >/=65 years | Statin use | No use | 6 months | Diagnosis of depression | RR = 0.85 95% CI = 0.79–0.90 P = NR | + |
| Köhler-Forsberg et al. (84) | Historical cohort | 387,954 adults | Statin prescription redemption | No prescription | 6.8 years | Diagnosis of depression | HR = 1.33 95% CI = 1.31–1.35 P = NR | - |
| Mansi et al. (85) | Historical cohort | 13,944 adults aged 30–85 years | Statin use | No use | 4.5 years | Diagnosis of mood disorder | OR = 1.02 95% CI = 0.94–1.11 P = 0.6 | = |
| Medici et al. (86) | Cohort | 12,176 ICU patients | Statin use | No use | 3 years | Diagnosis of depression or antidepressant prescription | RR = 1.04 95% CI = 0.96–1.13 P = NR | = |
| Molero et al. (87) | Historical cohort | 1,149,384 statin-users aged >/=15 years | Statin use | No use | 8 years | Diagnosis of depressive episode (unplanned hospital visit or specialised outpatient care) | HR = 0.91 95% CI = 0.88–0.94 P = NR | + |
| Otte et al. (88) | Cohort | 776 CAD patients | Statin use | No use | 6 years | Diagnosis of depression (PHQ>/=10) | OR = 0.62 95% CI = 0.41–0.95 P = 0.026 | + |
| Cross sectional | 965 CAD patients | Statin use | No use | – | Diagnosis of depression (PHQ>/=10) | OR = 0.66 95% CI = 0.45–0.98 P = 0.04 | + | |
| Pasco et al. (89) | Historical cohort | 345 women aged >/=50 years | Statin or aspirin use (self-reported) | No use | 10 years | Diagnosis of depression (first episode) | HR = 0.20 95% CI = 0.04–0.85 P = 0.03 | + |
| Case-control | 345 women aged >/=50 years | Statin use prior to depression onset (self-reported) | No use | 10 years | Diagnosis of depression (first episode) | OR = 0.13 95% CI = 0.02–1.02 P > 0.05 | = | |
| Redlich et al. (90) | Cohort | 4,607,990 adults aged >/=40 years | Statin prescription | No prescription | 3 years | Diagnosis of depression | OR = 0.92 95% CI = 0.89–0.96 P = 0.016 | + |
| Smeeth et al. (91) | Cohort | 729,529 adults aged >/=40 years | Statin prescription | No prescription | 4.3 years | New antidepressant prescription | HR = 1.01 99% CI = 0.96–1.06 P = NR | = |
| Stafford and Berk (92) | Cohort | 193 MI, PTCA, or CABG hospitalised patients | Statin prescription | No prescription | 9 months | Diagnosis of depression | OR = 0.21 95% CI = 0.052–0.876 P = 0.032 | + |
| Wee et al. (93) | Cohort | 3,792 TBI patients | Statin use in hyperlipidaemia (SHL) | Untreated hyperlipidaemia (UHL) or normolipidaemia (NL) | 3 years | Diagnosis of depression | SHL vs. NL HR= 1.02 95% CI = 0.55–1.89 P = 0.9611 SHL vs. UHL HR = 0.63 95% CI = 0.34–1.17 P = 0.1433 | = |
| Williams et al. (94) | Historical cohort | 836 adult men | Statin or aspirin use | No use | 6 years | Diagnosis of mood disorder | HR = 0.55 95% CI = 0.23–1.32 P = 0.18 | = |
| Case-control | 937 adult men | Statin or aspirin use | No use | – | Diagnosis of mood disorder | OR = 0.1 95% CI = 0.1–0.4 P < 0.001 | + | |
| Wium-Andersen et al. (95) | Historical cohort | 91,842 ACS patients, 91,860 matched individuals | Statin use | No use | 12 years | Diagnosis of early (<1 year) or late (1–12 years) depression or antidepressant prescription | Early depression ACS patients: HR = 0.94 95% CI = 0.86–0.94 P = NR Non ACS: HR = 1.04 95% CI = 0.96–1.12 P = NR Late depression ACS patients: HR = 0.96 95% CI = 0.82–0.90 P = NR Non ACS: HR = 1.00 95% CI = 0.95–1.06 P = NR | + |
| Wium-Andersen et al. (96) | Historical cohort | 147,487 ischemic stroke patients, 160,235 matched individuals | Statin use | No use | 1 year | Diagnosis of early (<1 year) or late (1–12 years) depression or antidepressant prescription | Early depression stroke patients: HR = 0.71 95% CI = 0.70–0.73 P = NR Non stroke: HR = 1.00 95% CI = 0.94–1.05 P = NR Late depression stroke patients: HR = 0.90 95% CI = 0.87–0.93 P = NR Non stroke: HR = 0.90 95% CI = 0.86–0.94 P = NR | + |
| Yeh et al. (97) | Historical cohort | 9,139 Asthma-COPD overlap syndrome patients | Statin use | No use | Up to 11 years | Diagnosis of depression | HR = 0.36 95% CI = 0.25–0.53 P < 0.001 | + |
| Young-Xu et al. (98) | Cohort | 371 CAD patients | Statin use | No use | 4 years | Diagnosis of depression (Kellner Symptom questionnaire >/=7) | OR = 0.63 95% CI = 0.43–0.93 P = NR | + |
| Case-control studies | ||||||||
| Yang (33) | Case-control | 366 hyperlipidaemic patients aged 40–79 years | Statin use | No use | – | Diagnosis of depression | OR = 0.4 95% CI = 0.2–0.9 P < 0.05 | + |
| Cross-sectional studies | ||||||||
| Agustini et al. (99) | Cross sectional | 19,114 community-dwelling participants aged >/= 70 years | Statin use (self-reported) | No use | – | Diagnosis of depression (CES-D >/= 8) | OR = 1.09 95% CI = 0.98–1.20 P = 0.11 | = |
| Boumendil and Tubert-Bitter (100) | Cross sectional | 17,244 adults | Simvastatin use (self-reported) | No use | – | Absenteeism due to depression | PR = 2.18 95% CI = 1.18–4.03 P = NR | – |
| Feng et al. (101) | Cross sectional | 2,804 adults aged >/= 55 years | Statin use (self-reported) | No use | – | Diagnosis of depression (GDS >/=5) | OR = 0.71 95% CI = 0.52–0.97 P = NR | + |
| Lindberg and Hallas (102) | Cross sectional | 166 users of antidepressant and statins | Statin use | No prescription | – | Antidepressant prescription redemption before vs after redemption of statin | RR= 1.06 95% CI = 0.79 to 1.45 P= NR | = |
| Williams et al. (103) | Cross sectional | 638 White Europeans, 695 South Asians and African-Caribbean | Statin prescription | No prescription | – | Diagnosis of depression (GDS >/=4) | White Europeans: OR = 0.54 95% CI = 0.26 to 1.13 P = NR South Asian and African-Caribbean: OR = 1.67 95% CI = 0.97–2.88 P = NR | = |
| Case series | ||||||||
| Cham et al. (104) | Case series | 11 male and 1 female patients | Statin treatment (simvastatin, atorvastatin, rosuvastatin, lovastatin, pravastatin) for 1 day to several months | – | – | – | Episodes of violent ideation, irritability, depression and suicide were reported. All 12 cases resolved upon discontinuation and recurred with re-challenge when attempted. Four cases met Naranjo criteria for definite causality, 4 for probable causality, 4 for possible causality. | – |
| Duits and Bos (105) | Case series | 4 female patients aged 32–59 | Simvastatin | – | – | – | Two patients developed psychotic, obsessive, depressive symptoms and suicidal/homicidal thoughts, and required treatment with clomipramine and cognitive therapy. One patient developed paranoid thoughts, suicidality, agitation and depressive symptoms after 4 days of simvastatin; symptoms resolved upon discontinuation. One patient suffered a depressive syndrome with psychotic features after 3 months of simvastatin; management with discontinuation, antipsychotic and antihypertensive medications was necessary. | – |
| Lechleitner et al. (106) | Case series | 4 female patients with primary hypercholesterolaemia, aged 44–66 | Pravastatin 10 mg for 12 weeks | - | - | - | Three patients developed mild-moderate depressive symptoms reversed by discontinuation. One patient developed severe psychiatric symptoms and suicidality, improved on discontinuation and didn't reoccurred with lovastatin treatment. | - |
| Rosenson Goranson (107) | Case series | 2 male hyperlipidaemic patients, aged 51–53 | Lovastatin 20–60 mg/die | – | – | – | Two patients developed sleep disturbances, anxious mood and irritability after several weeks of lovastatin treatment (20 mg/die and 60 mg/die); symptoms reversed 48 h after discontinuation, and reoccurred upon re-challenge, but not upon starting of pravastatin treatment. | – |
| Tatley and Savage (108) | Case series | Adverse reaction reports to New Zealand Centre for Adverse Reaction Monitoring | Statin treatment (simvastatin, atorvastatin, Fluvastatin, pravastatin) | – | – | – | 203 reports of psychiatric adverse events associated with statins (67 reports of mood disorders, 30 of cognitive disorders, 51 of sleep disorders, 14 of perception disorders, 107 other reactions such as asthenia, fatigue, lethargy). 57 reactions were severe. 34 had documented recurrence upon re-challenge | – |
*
The effect size of the main findings, either extracted from the study or calculated by the authors. Where this was not possible, we report the raw data.
ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CAD, coronary artery disease; CES-D, centre for epidemiological studies – depression scale; CI, confidence interval; COPD, chronic obstructive pulmonary disease; GDS, geriatric depression scale; HNC, head and neck cancer; HR, hazard ratio; ICU, intensive care unit; MD, mean difference; MI, myocardial infarction; PHQ, patient health questionnaire; PR, prevalence ratio; PTCA, percutaneous transluminal coronary angioplasty; OR, odds ratio; RR, relative risk; SD, standard deviation; TBI, traumatic brain injury.