Schizophrenia: An Inflammatory Disease That Can Be Treated With Aspirin?
Leslie Citrome, MD, MPH
Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders: Results From a Randomized, Double-Blind, Placebo-Controlled Trial
Laan W, Grobbee DE, Selten JP, et al.
J Clin Psychiatry. 2010;71:520- 527
This randomized, double-blind, placebo-controlled study enrolled 70 inpatients and outpatients from 10 psychiatric hospitals in the Netherlands with schizophrenia, schizoaffective disorder, or schizophreniform disorder (per Diagnostic and Statistical Manual of Mental Disorders, fourth edition). Exclusion criteria included illness duration longer than 5 years. Patients were randomly assigned to adjuvant treatment with aspirin, 1000 mg/d, or placebo for 3 months. Seventy percent of all patients received olanzapine, clozapine, or risperidone as their antipsychotic agent. For gastric protection, all patients received pantoprazole, 40 mg/d. Change in total Positive and Negative Syndrome Scale (PANSS) score from baseline to follow-up was the primary outcome. Baseline PANSS total and PANSS positive subscale scores were 73.1 and 17.6 for placebo and 71.1 and 16.5 for adjunctive aspirin, respectively. Observed were a 4.86-point (95% confidence interval [CI], 0.91-8.80 points) and 1.57-point (95% CI, 0.06-3.07 points) larger decrease in the aspirin group compared with the placebo group on the total and positive PANSS score, respectively. Treatment efficacy on total PANSS score was substantially greater in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded.
The authors state that inflammatory processes may play a role in the pathophysiology of schizophrenia and that prior work with adjunctive celecoxib demonstrated promise. However, celecoxib and other cyclooxygenase- 2 inhibitors have been associated with elevated cardiovascular risk and so are not optimal for use in patients with schizophrenia. Adjunctive aspirin is proposed as being more benign, with the added benefit of possessing cardioprotective effects. The authors suggest that aspirin may also reduce symptoms through other mechanisms, such as by antagonizing dysfunction of the N-methyl d-aspartate receptor, an area of active research for other adjunctive agents such as glycine, serine, and glycine transport inhibitors.
The authors report a mean modest reduction of the PANSS total score. However, "means can be meaningless"; unanswered are the number of patients who had a robust response, as represented by a large decrease in PANSS scores. Such categorical outcomes are important in understanding the potential clinical relevance of the findings presented in the paper. Effect size, as measured by the Cohen d for the total PANSS score, was approximately 0.5; although this is considered a medium effect, it does not answer the question of how many patients one must treat with adjunctive aspirin vs placebo before encountering one additional robust responder. Another caveat is that generalizability is limited to patients who are early in their disease course.
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