Predictive Factors of Treatment Resistance in First Episode of Psychosis: A Systematic Review

Background: Clinical and functional outcome improvement in psychotic disorders is a challenge for the investigators. Recent advances offered opportunities for ameliorating the course of the illness during its early stages and for identifying treatment-resistant patients. Patients who had not response to two different antipsychotics, administered at correct doses for a sufficient period, can be operationally considered treatment-resistant. Available evidence suggested that the response's trajectory to the antipsychotic treatment revealed that a small proportion of subjects are poor responders (8.2%), the majority of patients have a moderate response (76.4%), and only 15.4% can be considered rapid responders with the greatest magnitude of response. Patients with first episode of psychosis generally obtain a more favorable response profile. Nevertheless, in around 25% of these patients symptoms of psychosis persist with a worse long-term course of illness. Objectives: The aim of this review is to report current evidences on the main predictors of treatment non-response in patients at early stage of psychosis. Methods: We used a specific string that guaranteed a high sensitive search in pubmed. We included the following types of publications: randomized-controlled trials, observational studies, longitudinal studies, retrospective studies, case-control studies, open-label investigations, cohort studies, and reviews. Publications must concern predictors of treatment resistance in early psychosis. Results: Forty-seven records were included: 5 reviews, 3 meta-analyses, 22 longitudinal studies, 2 retrospective studies, 1 naturalistic study, 6 randomized controlled trials, 2 open-label studies, 2 case-control studies, 4 cohort studies, 2 retrospective studies. Several factors were identified as predictors of treatment resistance: lower premorbid functioning; lower level of education; negative symptoms from first psychotic episode; comorbid substance use; younger age at onset; lack of early response; non-adherence to treatment; and longer duration of untreated psychosis. The role of gender and marital status is still controversial. More evidences are needed about neurobiological, genetic, and neuroimaging factors. Conclusions: The identification of specific predictive factors of treatment resistance in patients with first episode of psychosis ameliorates the quality of clinical management of these patients in the critical early phase of schizophrenia.