The role of PANSS symptoms and adverse events in explaining the effects of paliperidone on social functioning: a causal mediation analysis approach

Abstract

To date, no study has evaluated the joint role of symptoms and adverse events as mediators of the effect of second-generation antipsychotics on patients’ social functioning. We used recently developed methods for mediation analysis with multiple mediators to clarify the interplay of adverse events and symptoms in explaining the effects of paliperidone (R code for implementing the mediation analysis for multiple mediators is provided). We used data from 490 participants in a 6-week randomized dose–response trial that assigned three fixed dosages of ER OROS paliperidone (3, 9, and 15 mg/day). The primary outcome was an individual’s score on the social performance scale assessed after 6 weeks. The sum of Positive and Negative Syndrome Scale (PANSS), weight gain, and extrapyramidal symptoms measured via the Simpson–Angus Scale after 5 weeks were investigated as potential mediators and effect modifiers of treatment effects. Results from mediation analyses showed that the improvements in social functioning are partly explained by reduction in PANSS symptoms. Suggestive evidence that adverse events could play a role as mediators was found. In particular, weight gain displayed a non-linear relationship with social functioning, whereby beneficial effects observed at small levels of weight gain were reduced in the presence of excessive weight gain. In conclusion, we found that the short-term effects of paliperidone on social functioning were dependent on the successful reduction in PANSS symptoms and possibly the occurrence of excessive weight gain, thus suggesting future directions for treatment and interventions.

The longitudinal effect of antipsychotic burden on psychosocial functioning in first-episode psychosis patients: the role of verbal memory

“…Both variables also fit with the definition of mediators as they ‘describe the process by which the intervention achieves its effects’ (Mackinnon, 2011). In addition to this, we may argue that the main potential mediating factors probably were controlled, as some authors have stated that psychopathology explains between 29% and 36% of the treatment effect on functioning, whereas they did not observe sizeable increases in weight gain (Zou et al, 2018). In the future, ongoing dose reduction v. drug-naïve controlled trials in patients with FEP will better define the nature of this association (O'Donoghue et al, 2018).…”

Serum periostin among infants with severe bronchiolitis and risk of developing asthma: A prospective multicenter cohort study

“…We constructed a directed acyclic graph to represent our possible causal structure linking IgE sensitization (the exposure) to the serum periostin level (the mediator) and asthma development (the outcome), along with the potential confounders listed above. To examine the direct and indirect (causal mediation) effects in a counterfactual framework, 30,31 we performed a causal mediation analysis using the R regmedint package. [32][33][34] This method enables us to examine the total effect and extent to which the effect of exposure on the outcome is direct (natural direct effect)…”

Participant Engagement and Symptom Improvement: Aripiprazole Tablets with Sensor for the Treatment of Schizophrenia

“…The PANSS and the PSP are not independent and have been shown to have correlated scores. [39][40][41] Associations have also been found between the PANSS and the CGI-I, the PANSS and the CGI-S, and the PSP and the CGI-S when 1 and Supplemental Table 2 for the full survey results and all means comparisons. a P-values were calculated using the Mann-Whitney U test.…”