Clinical validation of a combinatorial PharmAcogeNomic approach in major Depressive disorder: an Observational prospective RAndomized, participant and rater-blinded, controlled trial (PANDORA trial).

BACKGROUND: Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence. METHODS: Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks. DISCUSSION: This project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04615234. Registered on November 4, 2020.

Development and Validation of the Health of the Nation Outcome Scales-Residential Facility (HoNOS-RF).

The Health of the Nation Outcome Scale (HoNOS) (Lora et al. Epidemiol Psichiatr Soc 10(3):198-212, 2001) is widely used. However, clinicians have expressed concerns about its ability to describe severe mentally ill patients, as it does not consider some relevant clinical aspects. This study aims to develop and validate the HoNOS-Residential Facility (HoNOS-RF) in order to pursue a thorough assessment of patients admitted to psychiatric residential facilities (RFs). The final version of the HoNOS-RF was administered to 409 patients admitted to four RFs. Exploratory factor analysis, Cronbach' alpha (α), Intraclass Correlation Coefficients (ICC) were used to assess construct validity, internal consistency and reliability, respectively. Concurrent criterion validity was assessed through correlations with the Brief Psychiatric Rating Scale-Expanded Version (BPRS-E) (Roncone et al. Acta Psychiatric Scand 100(3):229-36, 1999), Personal and Social Performance Scale (PSP) (Morosini et al. Acta Psychiatric Scand 101(4): 323-29, 2000), and comparisons across diagnostic groups. The final version of the HoNOS-RF consisted of 31 items, grouped into the following eight factors (overall explaining 55% of the total variability): personal and interpersonal functioning; environment; behavior and burden of care; cognitive function; somatic problems; anxiety-depression symptoms; psychotic symptoms; and other psychiatric symptoms. The scale showed high internal consistency (α = .807), and the correlations with PSP and BPRS-E ranged from adequate to moderate. The ICCs were in the excellent range for almost all items. These findings support the validity and the reliability of the HoNOS-RF, thus it may be a useful tool for the assessment of patients admitted to RFs, as it addresses clinical aspects that were mostly not included in the original version.