Table 2 Potential risks of aspirin usage in MS

Cerebral bleeding/hemorrhagic strokes)

There is an increase in the incidence of intracranial hemorrhages with antiplatelet treatment [30–32, 79]. Because MS patients can have a compromised BBB [7, 8], the risk of intracerebral bleeding in MS may be greater with ASA usage.

Platelets/coagulation may act to limit BBB damage in MS. ASA’s antiplatelet/anticoagulation properties potentially increase the likelihood that BBB leakage could be prolonged or worsened.

Mitochondrial function complex I inhibition

Mitochondrial complex I activity is reduced in MS [34, 35]. ASA may inhibit complex I [33], and the effect may be more pronounced with glutathione depletion [140], which is thought to occur in MS [141, 142]. Inhibition of complex I may lead to an increase in ROS production [143].

Direct inhibition of complex I by ASA [33].

Increased gastrointestinal bleeding

ASA treatment has been found to increase the incidence of gastrointestinal and other extracranial bleeding [31], and risk increases with patient age [198].

Anticoagulation (antiplatelet); ASA blocks the synthesis of gastroprotective prostaglandins via inhibition of COX-1, which increases gastrointestinal bleeding [198].

Increased risk of bleeding with concurrent use of ASA with an antidepressant (SSRI)

Both ASA and the antidepressant class selective serotonin reuptake inhibitors (SSRIs) increase risk of bleeding by themselves. Following an acute myocardial infarction, the combination of ASA and SSRI treatment increases the risk of bleeding in patients compared to ASA alone [191].

Anticoagulation (antiplatelet)

Adverse effects relative to depression

Concurrent use of ASA with citalopram may lead to an increased risk of adverse events, such as anxiety, akathesia, and suicidal behavior [189]. Also, NSAIDs may interfere with the antidepressant effects of SSRIs, preventing depressed patients from achieving relief [190].

The mechanism is unknown, but possibly NSAIDs are blocking the production of a protective mediator, for example, anti-inflammatory cytokine [189].

Hearing loss and tinnitus

Although rare, hearing loss and tinnitus have been reported with high dosages of salicylate (6–8 g or more per day) [200, 203, 204]. In men, regular usage of ASA also has been found to heighten the risk for loss of hearing, and the effect is more pronounced in younger individuals [213].

The mechanism is not known, but may be through suppressing GABAergic inhibition [203, 204]; sodium salicylate also affects cochlear function [200, 204]

Respiratory attacks, asthma

Approximately 10 % [207] to 21 % [206] prevalence of ASA-induced asthma in adult asthmatic patients and 5 % prevalence in asthmatic children, based on both retrospective/self-report studies and provocation studies [206].

COX enzyme inhibition leading to decreased PGE₂ and enhanced leukotriene and histamine production [198, 206, 210].