The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.

To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.

Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.

Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76–0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69–0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.

These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

In Australia, 18F-fluorodeoxyglucose positron emission tomography with low-dose computed tomography (FDG-PET/CT) is currently only funded for cancer staging-related indications. A recent multicenter randomized trial demonstrated that FDG-PET/CT, compared with standard of care computed tomography (CT) imaging, improved antimicrobial management and the outcomes of patients with persistent and recurrent neutropenic fever. There is potential value in expanding the use of FDG-PET/CT as a diagnostic tool for this high-risk population. We conducted an economic evaluation from a healthcare perspective alongside the randomized trial and compared FDG-PET/CT with standard CT up to 6 months after the scans.

Case report forms were used to collect resource utilization data and length of hospitalization. Effectiveness was measured as the number of patients with antimicrobial rationalization and quality-adjusted life-years (QALYs) derived from patient-reported trial-based health-related quality of life. Generalized linear models (GLM) were used to analyze costs and outcomes. Incremental cost-effectiveness ratios (ICERs) for each of the outcomes were calculated and interpreted as the cost per patient with antimicrobial rationalization and cost per QALY gained. To account for sampling, we performed bootstrapping with 1,000 replications using the recycled predictions method.

The adjusted healthcare costs were lower in the FDG-PET/CT group (mean AUD49,563, 95% confidence interval [CI]: 36,867, 65,133; equivalent to USD34,268, 95% CI: 25,490, 45,033) compared with the standard CT group (mean AUD57,574, 95% CI: 44,837, 73,347; equivalent to USD39,807, 95% CI: 31,000, 50,712). The magnitude of differences in QALYs between the two groups was small (0.001; 95% CI: -0.001, -0.001). When simulated 1,000 times, our analysis showed that across both outcomes FDG-PET/CT was the dominant strategy as it was cheaper and had better outcomes than standard CT in 74 percent of simulations.

FDG-PET/CT is cost effective when compared with standard CT for investigating persistent or recurrent neutropenic fever in high-risk patients. Aligning economic evaluations with clinical studies is key to an integrated evidence generation approach for supporting funding for FDG-PET/CT in this patient group.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.