Association Between Childhood Adversity and Functional Outcomes in People With Psychosis: A Meta-analysis.

BACKGROUND AND HYPOTHESIS: Despite the accepted link between childhood adversity (CA) and psychotic disorders, evidence on the relationship between CA and poor functional outcome remains less consistent and has never been reviewed quantitatively. The aim of this meta-analysis was to systematically examine the association between CA and functional outcomes in people with psychotic disorders. STUDY DESIGN: The study protocol was registered on the International Prospective Register of Systematic Reviews (CRD42021254201). A search was conducted across EMBASE, MEDLINE, PsycINFO, and Cochrane Libraries (CENTRAL) using search terms related to psychosis; CA (general, sexual abuse, physical abuse, emotional abuse, physical neglect, and emotional neglect); and functional outcomes (social, occupational, and general functioning [GF]). We conducted random-effects models, sensitivity and heterogeneity analyses, meta-regressions, and we assessed quality. STUDY RESULTS: Our meta-analysis comprised 35 studies, including 10 568 cases with psychosis. General CA was negatively associated with GF (28 studies; r = -0.109, 95%CI = -0.161 to -0.05, P < .001), with greater effects in prospective data (10 studies; r = -0.151, 95% CI = -0.236 to -0.063, P = .001). General CA was also associated with social functioning (r = -0.062, 95% CI = -0.120 to -0.004, P = .018) but not occupational outcomes. All CA subtypes except sexual abuse were significantly associated with GF, with emotional and physical neglect showing the largest magnitudes of effect (ranging from r = -0.199 to r = -0.250). CONCLUSIONS: This meta-analysis provides evidence for a negative association between general CA, specific subtypes, and general and social functional outcomes in people with psychosis.

Comparison of aripiprazole and risperidone effectiveness in first episode non-affective psychosis: Rationale and design of a prospective, randomized, 3-phase, investigator-initiated study (PAFIP-3).

BACKGROUND: Selecting the most effective treatment represents a critical challenge with the potential of modifying the long-term prognosis of individuals suffering a first break of psychosis. Head-to-head clinical trials comparing effectiveness among antipsychotic drugs in individuals with a first-episode of non-affective psychosis (FEP) are scarce. METHODS: The rationale and design of a 3 phases clinical trial (PAFIP-3, NCT02305823) comparing the effectiveness of aripiprazole and risperidone, and to additionally assess the benefits of an early use of clozapine in primary treatment-resistant patients is reported. The design encompasses of 5 work packages (medication algorithm, cognitive functioning, psychoeducation/vocational functioning, imaging and biological markers) addressing critical issues and needs of first episode psychosis individuals and their cares. The primary outcome measure was treatment effectiveness assessed by all-cause treatment discontinuation rate. RESULTS: 266 individuals have been included in the randomization study phase I (risperidone vs. aripiprazole). At 3 months, the retention rate was of 94% (249/266), 48(19.3%) patients have gone through phase II (olanzapine treatment), and 7(2.8%) entered the clozapine phase (phase III). DISCUSSION: The PAFIP 3 clinical trial may provide relevant information about clinical guidelines to optimally treat patients with a first episode of non-affective psychosis and the benefits and risks of an early use of clozapine in treatment resistant patients. Clinicaltrials.gov: NCT02305823.