Table 1.

Table of clinical trials featuring mood as an endpoint

Reference	Exposure/Duration	Patients	Outcome/Assessment	Result
Harrison, 1994 [27]	Simvastatin 40 mg/day vs. pravastatin 40 mg/day vs. placebo; 2 week placebo run-in, 4 week treatment phase, 4–6 week washout	25 healthy volunteers, average age 23.8 years; excluded those with personal or family history psychiatric disease, or evidence of current depression	Hospital Anxiety Depression Scale at conclusion	No effect
Muldoon, 2000 [31]	Lovastatin 20 mg/day vs. placebo for 6 months	209 healthy adults with LDL-C >4.14 mmol/L (160 mg/dL), aged 24–60 years; excluded those with schizophrenia, use of psychotropic medications	Assessments at baseline and conclusion of mood, hostility, hopelessness, anger, and social function using neuropsychological test battery (16 tests), interviews, and daily diary assessments	No effect; in addition, no signal of worsening for those with the greatest LDL-C reduction or those reaching the lowest LDL-C levels.
Carlsson, 2002 [28]	Pravastatin 20 mg/day for 6 months then pravastatin + tocopherol (group 1) or tocopherol for 6 months then both medications for an additional 6 months	41 community-dwelling men and women >70 years old with LDL-C ≥3.62 mmol/L (140 mg/dL); 3 subjects used antidepressants	Health perception and depression (Geriatric Depression Scale) were assessed at baseline, 6 months, and 1 year	No effect at 6 months or 1 year; in addition, no changes by lipid levels.
Ormiston, 2003 [29]	Atorvastatin 10–20 mg/day, lovastatin 20–40 mg/day or placebo for 52 weeks (upon unblinding, it was revealed no patients received placebo)	12 subjects, aged 33–80 years; mean total cholesterol at baseline 7.27 mmol/L (281 mg/dL)	Psychological variables were measured at 4 weeks and 52 weeks using Beck Depression Inventory, Buss-Durkee Hostility Inventory, and the Barrett Impulsivity Scale	Week 4: No effect on depression or hostility; mild increase in impulsivity, not significantly correlated with cholesterol lowering. Week 52: Impulsivity returned to baseline. No change in hostility. Depression mildly but significantly improved compared to baseline.
Hyyppa, 2003 [30]	Mediterranean-style diet and/or simvastatin 20 mg/day for 12 weeks	120 hyperlipidemic but otherwise healthy men aged 35–64 years	Psychological distress assessed by Brief Symptom Inventory that assessed somatization, depression, anxiety, hostility, phobic anxiety and obsessive– compulsive behavior; Aggression was assessed with two questionnaires based on the Strauss Scale of Aggression Questionnaire (completed by subject and partner or cohabitant).	Simvastatin resulted in an increase in depression (p=0.016), and somatization (p=0.034), without changes in the anxiety, hostility scores. Aggression increased by self-report (p=0.049) but not by report from partners
Morales, 2006 [32]	Simvastatin, up to 20 mg/day or placebo for 15 weeks after 4–6 week run-in diet phase	80 participants with an average age of 70 years and high normal/mildly elevated cholesterol	Center for Epidemiological Studies Depression Scale (CES-D), Structured Clinical Interview for DSM, Apathy Evaluation Scale Profile of Mood States, Daily diaries incorporating Lawton Positive Affect and Negative Affect rating scales	No change in CES-D scores Diary data showed time-dependent, cholesterol-related decreases in self-reports of positive affect in the simvastatin group.
Ghanizadeh, 2013 [33]	Lovastatin up to 30 mg/day, lovastatin up to 30 mg/day + fluoxetine up to 40 mg/day, or fluoxetine up to 40 mg/day + placebo	68 participants with diagnosed Major Depression Disorder and without “serious uncontrolled medical conditions” such as hyperthyroidism, hypothyroidism, epilepsy, active substance abuse, diabetes, hypertension, or active suicidal ideation	Hamilton Depression scale via face-to-face interviews at baseline, week 2, and week 6.	Fluoxetine plus lovastatin decreased Major Depressive Disorder symptoms more than fluoxetine plus placebo