Table 2 Summary of key randomized controlled trials evaluating the effects of aspirin use on mental illness and symptoms.

Dinnerstein, 1970

DB-RCT

ASA 600 mg + placebo 'energizer'/'tranquilizer' versus lactose 600 mg + placebo 'energizer'/'tranquilizer'

80 healthy male college students

CMS

ASA had no direct and fixed effect on mood, but acts to modulate the effect of placebo or other contextual variables

Lieberman, 1987

DB-RCT

2* to 6*sessions: caffeine 64 mg, or ASA 800 mg, or caffeine 64 mg + ASA 800 mg, or caffeine 128 mg + ASA 800 mg, or placebo in Latin-square design

20 healthy men 18 to 35 years old, caffeine intake <400 mg/day, non-smokers

6 sessions PMS, visual analog mood scales, NVMS, SSS, and performance tests

Mean and SEM

Caffeine alone and caffeine +ASA improved vigilance, self-reported efficiency and mood compared with ASA alone and placebo

Kang, 2007; Women's Health Study

Cohort study within a DB-RCT

ASA 100 mg or placebo on alternate days

6,377 women >65 years old

TICS-M, immediate and delayed recalls of the EBMT and delayed recall of the TICS-M, 10-word list and category fluency (naming as many animals as possible in 1 minute)

Mean and SD

ASA users did not differ in overall performance in any of the cognitive assessments, from the 1* assessment (after 5.6 years) to the 3* (after a mean 9.6 years), or in their average cognitive decline during 3 to 6 years of follow-up. ASA users performed better in category fluency, particularly in the final assessment

Kudielka, 2007

DB-RCT

ASA 100 mg, or propranolol 80 mg, or ASA 100 mg + propranolol 80 mg, or placebo

73 healthy subjects

TSST. Cortisol from six saliva samples taken before and after the stress exposure

Mean and SD

5 days: groups did not differ in their cortisol responses

Clinical population

Clarke, 2003; VITAL trial collaborative group; dementia or MCI

DB-RC; 4-week placebo-controlled run-in period before randomization + 12-week treatment

ASA 81 mg, or placebo AND folic acid 2 mg + vitamin B12 1 mg, or placebo AND vitamin E 500 mg + vitamin C 200 mg, or placebo in 2 × 2 × 2 factorial design

149 NII, 12 to 26 patients MMSE score or <27 patients TICS-M score, naïve to study medications. Follow-up: 137 for biochemical outcomes, 128 for cognitive outcomes

TICS-M, MMSE, ADAS

Median percentage reduction

12 weeks of ASA was effective in reducing biochemical factors (thromboxane) associated with cognitive impairment in people at risk of dementia. No effect of treatment on cognitive function

AD2000, 2008; Alzheimer's disease

OL-RCT

ASA 75 mg yes/no

310 NII

MMSE, behavioral symptoms

Mean and SD

At 3 -year follow-up: no differences in scores, significantly higher risk of bleeding

Price, 2008; asymptomatic atherosclerosis

DB-RCT

ASA 100 mg or placebo

3350 participants 50-75 years old

Summary cognitive score = tests of memory, executive function, non-verbal reasoning, mental flexibility, and information processing

Mean and SD

At 5-year follow-up: no differences

Gałecki, 2009; first depressive episode

OL-RCT

fluoxetine 20 mg, or fluoxetine 20 mg + ASA 150 mg

77 participants

HDRS

No differences in HDRS between fluoxetine group and fluoxetine + ASA group

Laan, 2010; schizophrenic spectrum disorders

DB-RCT

ASA 1000 mg/day or placebo adjuvant to antipsychotic + pantoprazole 40 mg/day

70 adults

PANSS ≥60, 2 items ≥4, illness duration <10 years. 2-week placebo run-in period, and only those who achieved over 80% compliance were randomized

PANSS

Mean and SD

Adjuvant ASA reduced overall psychopathology and positive symptoms at 3 months. No significant results in other subscales. ASA had greater effect on overall psychopathology in individuals with more altered immune function. ASA significantly reduced overall psychopathology in individuals with the lowest Th1:Th2 ratios