ASPIRIN (ACETYLSALICYLIC ACID)
Background

Folk remedies containing salicylic acid have been used for centuries to treat pain and fever. Acetylsalicylic acid was first synthesized in Europe in the mid-19th century. The patent for aspirin, owned by Bayer, expired in 1917 in the United States, and it has been widely available over-the-counter since that time.

Mechanism of Action

Aspirin is a non-steroidal anti-inflammatory drug (NSAID) thought to work by blocking cyclooxygenase (COX), an enzyme needed for the synthesis of prostaglandins and thromboxanes. It is thought to block COX-1 and COX-2 equally. This interferes with pain transmission and the aggregation of platelets, thereby decreasing clots and being useful as a prophylactic against heart attacks. Prostaglandins also play an important role with N-methyl-D-aspartate acid (NMDA) receptors, important in glutamate transmission. Other possible mechanisms of action include neuroprotection, effects on membrane phospholipids, and effects on pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha.

Use in Schizophrenia

C-reactive protein (CRP) is an enzyme that is a marker of chronic inflammation. At least three studies have reported that CRP is elevated in individuals with schizophrenia, suggesting that inflammation is an important part of the disease process.5–7 In addition, genes associated with inflammation are upregulated in brain tissue in schizophrenia8, and some antipsychotics have been shown to affect CRP.9

In the only published study to date, 70 patients with schizophrenia spectrum diagnoses were randomized to aspirin 1,000mg/day or placebo, in addition to their regular medication, for 3 months. All the patients had been sick for less than 10 years. Those on aspirin had a significant decrease in positive PANSS scores and a nonsignificant decrease in negative symptoms. Cognitive symptoms were not improved. The patients who showed the best response were those with the highest levels of some markers of inflammation.10 To minimize effects of the aspirin on the stomach, patients were also given a proton pump inhibitor. SMRI is supporting a large, ongoing, double-blind, follow-up study using aspirin as an adjunct medication for schizophrenia.

Use in Bipolar Disorder

CRP was reported to be elevated in a study of 122 outpatients with bipolar disorder.11 Other studies have associated bipolar disorder with inflammation through gene expression or altered cytokine levels.12 A study of rats suggested that lithium’s effectiveness may be attributable in part to its anti-inflammatory action.13 To date, no study has been published on the use of aspirin in bipolar disorder, but SMRI is supporting a double-blind study in progress.

Assessment

Aspirin is a relatively safe drug except for individuals who have ulcers or other bleeding problems. It should not be used without medical authorization for patients taking inhibitors of blood clotting, such as warfarin (Coumadin) or clopidogel (Plavix). Its possible role in the treatment of schizophrenia and bipolar disorder is still to be determined, but may be most useful in patients with elevated CRP or other inflammatory markers.