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Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive inflammation.

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Palliative care has several tools and questionnaires which are commonly used for patient-related outcomes and prognosis. As an example, the Surprise Question (I would or would not be surprised that this person would have died in a year) has been used as a screen for palliative care referral but also used as a prognostic tool. Diagnostic tests, prognostic tools, and tools for gauging outcomes have certain sensitivity and specificity in predicting a diagnosis or outcome. Clinicians often use positive and negative predictive values in judging the merits of a diagnostic tool or questionnaire. However positive and negative predictive values are highly dependent on the prevalence of disease or outcome in a population and thus are not portable across studies. Likelihood ratios are both portable across populations but also provide the strength of the diagnostic or predictive measure of a test or questionnaire. In this article, we review the value and limitations of likelihood ratios and illustrate the value of using likelihood ratios using 3 studies centered on the Surprise Question published in 2022.