Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years

Veronese, Nicola; Koyanagi, Ai; Stubbs, Brendon; Solmi, Marco; Fornaro, Michele; Fernandes, Brisa Simões; Müller, Christoph; Thompson, Trevor; Carvalho, André F.; Maggi, Stefania

doi:10.1002/gps.4767

Cited by 11 publications

(25 citation statements)

References 39 publications

(75 reference statements)

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“…Epidemiological studies suggest that people taking aspirin or statins might be less likely to have concurrent depression [26][27][28][29][30], although the evidence is inconsistent, with some negative reports [31]. While there are positive randomised controlled trials of statins for the treatment of depression [32][33][34], and meta-analytic evidence for their effectiveness [35], no studies have investigated their therapeutic potential among youth.…”

Section: Introductionmentioning

confidence: 99%

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Berk

Mohebbi

Dean

et al. 2020

BMC Med

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Background: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and antiinflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). Methods: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. Results: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (− 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (− 4.2, 95% CI (− 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. Conclusions: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.

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Section: Introductionmentioning

confidence: 99%

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Berk

Mohebbi

Dean

et al. 2020

BMC Med

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“…Using a random-effects model, the pooled HR of the three cohort studies [14,17,21] was 0.624 (95% CI: 0.0503 to 1.198, p = 0.033), supporting a reduced risk of depression with ASA exposure. The high heterogeneity (I 2 = 79.25%), as seen in Figure 2, could be due to the different population characteristics studied (e.g., patients being at different phases of illness, of differing demographics, and on different treatments).…”

Section: Resultsmentioning

confidence: 95%

“…The salient details of the studies are summarized in Table 1. There were two randomized, placebo-controlled, double-blind trials and two key cohort studies (the Geelong Osteoporosis Study [14] and the Osteoarthritis Initiative (OAI) study [17]). A meta-analysis was limited due to the small number of studies and dissimilar study designs and outcome measures.…”

Section: Resultsmentioning

confidence: 99%

Clinical Role of Aspirin in Mood Disorders: A Systematic Review

Ramamoorthy

Loke

et al. 2019

Brain Sciences

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Worldwide, depression and bipolar disorder affect a large and growing number of people. However, current pharmacotherapy options remain limited. Despite adequate treatment, many patients continue to have subsyndromal symptoms, which predict relapse in bipolar illness and often result in functional impairments. Aspirin, a common nonsteroidal anti-inflammatory drug (NSAID), has purported beneficial effects on mood symptoms, showing protective effects against depression in early cohort studies. This systematic review thus aimed to investigate the role of aspirin in mood disorders. Using the keywords (aspirin or acetylsalicy* or asa) and (mood or depress* or bipolar or mania or suicid*), a comprehensive search of PubMed, EMBASE, Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found 13,952 papers published in English between 1 January 1988 and 1 May 2019. A total of six clinical studies were reviewed. There were two randomized, placebo-controlled, double-blind trials and populations drawn from two main cohort studies (i.e., the Geelong Osteoporosis Study and the Osteoarthritis Initiative study). Using a random-effects model, the pooled hazard ratio of the three cohort studies was 0.624 (95% confidence interval: 0.0503 to 1.198, p = 0.033), supporting a reduced risk of depression with aspirin exposure. Overall, the dropout rates were low, and aspirin appears to be well-tolerated with minimal risk of affective switch. In terms of methodological quality, most studies had a generally low risk of bias. Low-dose aspirin (80 to 100 mg/day) is safe, well-tolerated and potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression. Due to its ability to modulate neuroinflammation and central nervous system processes, aspirin may also have valuable neuroprotective and pro-cognitive effects that deserve further exploration. Further randomized, controlled trials involving the adjunctive use of aspirin should be encouraged to confirm its therapeutic benefits.

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“…A total of 56 027 cases of depression were investigated in this meta‐analysis. For the ascertainment of depression, four studies 12,18,19,25 used self‐reported measures of depression, three studies 17,20,22 used the Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, three studies 21,23,26 used the International Classification of Disease, 10th revision, one study 24 used hospital contact with depression or filled prescriptions for antidepressant medication, and one study 27 used self‐report of a medical diagnosis of depression or the use of antidepressants.…”

Section: Resultsmentioning

confidence: 99%

“…As for the ascertainment of aspirin use, eight articles 12,17‐20,25,27 used self‐report questionnaires and the other four studies conducted in Denmark 21,23,24,26 used objective assessment tools such as the Danish Prescription Registry Anatomical Therapeutic Chemical (ATC) codes. Regarding the duration of aspirin use, the average duration of aspirin use was ≥5 years in nine articles 12,17,20,21,23‐27 . In one study, 18 the average duration of aspirin use was ≥2 years.…”

Section: Resultsmentioning

confidence: 99%

The association between aspirin use and depression: a systematic review and meta‐analysis of observational studies

Kim

Jung

2020

Pharmacoepidemiology and Drug

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Purpose Many clinical trials and observational studies have been conducted under the premise that the anti‐inflammatory effect of aspirin may prevent depression. These studies, however, showed inconsistent results. To inspect the association between aspirin use and depression, we conducted a meta‐analysis of observational studies. Methods In August 2019, two authors independently searched PubMed, EMBASE, and PsycINFO to retrieve observational epidemiological studies presenting an association between aspirin use and depression. Case‐control and cohort studies were included, and odds ratios (ORs) or relative risks (RRs) with 95% confidence intervals (CIs) for the risk of depression were estimated using a random‐effects model. In addition, number needed to harm (NNH) was calculated to measure the rates of depression. Results In total, 12 observational studies—five case‐control studies and seven prospective cohort studies—were included in this meta‐analysis. The random‐effects model demonstrated a significant association between aspirin use and depression (OR/RR 1.10; 95% CI: 1.05‐1.16) with insignificant heterogeneity (I2 = 23.3%). The risk estimates of depression from prospective cohort studies were similar (RR 1.11; 95% CI: 1.08‐1.14), and heterogeneity was not observed (I2 = 0.0%). In the subgroup meta‐analysis, a duration of aspirin use ≥5 years and a dosage ≥500 mg daily were also associated with depression. The NNH for depression with aspirin use >5 years was 103 (95% CI 91‐111) indicating that observed event is rare. Conclusions Aspirin use was associated with depression in the present meta‐analysis. One of the major limitations is the lack of detail and consistency with respect to exposure verification in the included papers. Another limitation is the lack of randomized controlled studies and prospective cohort studies.

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Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years

Abstract: Our study found that prescription of aspirin offered no significant protection against incident depressive symptoms. Whether aspirin is beneficial in a subgroup of depression with high levels of inflammation remains to be investigated in future studies.

Cited by 11 publications

References 39 publications

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Clinical Role of Aspirin in Mood Disorders: A Systematic Review

The association between aspirin use and depression: a systematic review and meta‐analysis of observational studies

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