Clinical correlates of early onset antipsychotic treatment resistance

Abstract

Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS. Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

The ever-growing case for clozapine in the treatment of schizophrenia: an obligation for psychiatrists and psychiatry

“…Current findings also imply that some secondary forms of treatment resistance might be preventable. Interestingly, there is tentative evidence that SGA-LAIs – the most effective first-line treatment regarding treatment adherence and relapse prevention [34] – might delay the onset of TRS by 15 months [35]. Unfortunately, this opportunity is presently squandered because of widespread underutilization of SGA-LAIs [34].…”