Does Administration of Low-Dose Aspirin Enhance the Efficacy of Psychotropic Drugs in Patients with Bipolar Disorder, Schizophrenia, and Schizoaffective Disorder?

<b>Background/Objectives:</b> An extensive body of data suggests that inflammation may contribute to the pathophysiological mechanisms of psychiatric illness. Circumstantial evidence implied that low-dose aspirin (LDA) may enhance the therapeutic efficacy of psychotropic drugs. We examined whether LDA administration with psychotropic medications is associated with medication regimen stability and other therapeutic effects in patients with bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). <b>Methods:</b> This retrospective study analyzed data from Clalit Health Services' Southern District database in Israel, including 1924 patients treated between 2017 and 2019. The Study Group consisted of patients treated with LDA plus psychotropic medications, whereas the Control Group included patients treated only with psychotropic medications. Study outcomes included suicide attempts and pharmacotherapy-related negative events, defined as psychotropic dose escalation, augmentation, or switching. <b>Results:</b> The study group included 137 patients (55% males, age 63.3 ± 12.3 years), and the control group included 1787 patients (60% males, age 47 ± 16.9 years). Significant differences were observed across nearly all outcomes, favoring the LDA co-treatment group. Patients in the study group exhibited lower rates of medication dosage increase (40 [29%] vs. 726 [40.5%], <i>p</i> = 0.01); fewer changes and/or additions of psychotropic medications (37 [26.9%] vs. 778 [43.5%], <i>p</i> < 0.001); and a non-significantly lower rate of suicide attempts (0 [0%] vs. 16 [0.9%], <i>p</i> = 0.53). <b>Conclusions:</b> Overall, LDA co-treatment was associated with better clinical outcomes among patients with BD, schizophrenia, and SAD. Follow-up large-scale epidemiological studies and prospective randomized clinical trials are needed to examine the therapeutic potential of add-on LDA to psychotropic medications.