Background
Schizophrenia is a serious mental illness that affects around 21 million people worldwide. The symptoms of schizophrenia are typically classified into positive (e.g. hallucinations and delusional thoughts), negative (e.g. withdrawal and difficulty with social interaction) and cognitive (e.g. poor attention and restricted working memory) groups. These symptoms cause distortions in an individual's behaviour, thinking, emotions, sense of self and perception. Usually, antipsychotic medicines are used for treating the symptoms of schizophrenia.
In recent years, inflammation (swelling) in a person's brain was linked to the symptoms that accompany schizophrenia. Aspirin is an affordable medicine which acts against inflammation and, therefore, it is thought it could help reduce the symptoms of schizophrenia. In this review, we looked at the effects of using aspirin as an add-on treatment for people with schizophrenia.
Study characteristics
After searching Cochrane Schizophrenia's database in March 2018 and assessing the search results, we included one randomised controlled trial (clinical studies where people are randomly put into one of two or more treatment groups) from the Netherlands (70 participants) and one from Iran (60 participants). Both trials used aspirin as an add-on treatment to standard antipsychotic medication and compared it with placebo (a dummy treatment), also as an add-on to standard treatment.
Key results
Participants receiving aspirin had slightly better results for their mental state, which was measured with the Positive and Negative Symptom Scale (PANSS). For side effects related to stomach problems, there seemed to be no clear difference between the groups. The same applied to changes in hospital status and leaving the study early. However, all these results were based on analyses of very poor data and graded as very low-quality evidence. No trial gave usable information on cognitive functioning or quality of life.
Quality of the evidence
This review was based on results from only two small trials, which made it impossible to say whether aspirin would be a good treatment option for people with schizophrenia. More information from the trials that are underway could strengthen the results of this analysis.
We highlighted the evidence that some pioneering researchers feel this question is important enough to merit testing in randomised trials. However, we also highlighted that the evidence produced from these trials was weak and inconclusive. It was impossible to draw clear conclusions on the therapeutic value of aspirin for schizophrenia from these short, small and limited trials.
Schizophrenia is a serious chronic mental illness affecting an estimated 21 million people worldwide and there is increasing evidence linking inflammation in the brain to the pathophysiology of schizophrenia. Antipsychotic drugs are the conventional treatment for people with schizophrenia but are not always fully effective. Acetylsalicylic acid (aspirin) is a non-steroidal anti-inflammatory drug (NSAID) with properties that inhibit the proinflammatory status of the brain. Using aspirin as an adjunct (add-on) treatment to antipsychotics or as a stand-alone treatment could be a novel, relatively inexpensive option for people with schizophrenia.
To review the effects of acetylsalicylic acid (aspirin) as adjunct (add-on) or as stand-alone treatment for people with schizophrenia.
We searched the Cochrane Schizophrenia Group's Trials Register (last search 8 March 2018) which is based on regular searches of MEDLINE, Embase, PubMed, CINAHL, BIOSIS, AMED, PsycINFO and registries of Clinical Trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register.
Randomised clinical trials focusing on aspirin for people with schizophrenia.
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat (ITT) basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
We included two studies, both comparing the effects of adding aspirin to standard antipsychotic treatment with adding placebo to standard antipsychotic treatment. We were hoping to find high-quality data for seven main outcomes of importance: clinically important change in global state, mental state, cognitive functioning and quality of life, numbers leaving the study early, incidence of gastrointestinal adverse events and hospital admission. Clinically important change data were not reported. Global state data were reported by one study as 'unspecified problem necessitating change in dose or type of antipsychotics'; there was no clear difference between treatment groups for this outcome (RR 0.75, 95% CI 0.30 to 1.88; studies = 1; participants = 70; very low-quality evidence). Both trials measured mental state using the Positive and Negative Symptom Scale (PANSS), and mean total PANSS endpoint scores favoured the adjunct aspirin group in the medium term (MD –6.56, 95% CI –12.04 to –1.08; studies = 2; participants = 130; very low-quality evidence). Less than 10% of each group's participants left the studies early (for any reason) and by around three months there was no clear difference between numbers leaving early from the aspirin group compared to numbers leaving early from the placebo group suggesting aspirin is acceptable (RR 1.12, 95% CI 0.40 to 3.14; studies = 2; participants = 130; very low-quality evidence). There was some gastric upset in both groups but rates were not clearly different between the treatment groups (RR 1.03, 95% CI 0.55 to 1.94; studies = 1; participants = 70; very low-quality evidence). We are unclear if 'change in hospital status' is an unfavourable outcome or not as one study reported equivocal data (RR 0.56, 95% CI 0.05 to 5.90; studies = 1; participants = 70; very low-quality evidence). It should be noted that all the above results were based on data of very low-quality and were difficult to interpret for clinicians or patients, and that the two studies, completed in the last decade, failed to report any usable outcomes on cognitive functioning or quality of life.