Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data

Background: Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear. Objectives: To investigate whether antipsychotic discontinuation is associated with the prescr...

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Main Authors: Rashmi Patel, Aimee Brinn, Jessica Irving, Jaya Chaturvedi, Shanmukha Gudiseva, Christoph U. Correll, Paolo Fusar-Poli, Philip McGuire
Format: Article
Language:English
Published: SAGE Publishing 2023-11-01
Series:Therapeutic Advances in Psychopharmacology
Online Access:https://doi.org/10.1177/20451253231211575
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author Rashmi Patel
Aimee Brinn
Jessica Irving
Jaya Chaturvedi
Shanmukha Gudiseva
Christoph U. Correll
Paolo Fusar-Poli
Philip McGuire
author_facet Rashmi Patel
Aimee Brinn
Jessica Irving
Jaya Chaturvedi
Shanmukha Gudiseva
Christoph U. Correll
Paolo Fusar-Poli
Philip McGuire
author_sort Rashmi Patel
collection DOAJ
description Background: Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear. Objectives: To investigate whether antipsychotic discontinuation is associated with the prescription of particular antipsychotics and particular adverse effects. Design: Retrospective cohort study. Methods: We assembled de-identified electronic health record (EHR) data from 2309 adults with FEP who received care from the South London and Maudsley NHS Foundation Trust between 1st April 2008 and 31st March 2019. Associations between antipsychotic medications, clinician-recorded side effects and treatment discontinuation were investigated across a mean follow-up period of 34.2 months using Cox regression. Results: The mean age of patients was 26.7 years and 1492 (64.6%) were male. Among first prescribed antipsychotic medications, discontinuation occurred earlier with haloperidol [hazard ratio (HR) = 2.78, 95% CI = 1.69–4.60] and quetiapine (HR = 1.43, 95% CI = 1.16–1.80) than with olanzapine. Discontinuation occurred sooner when there was evidence of extrapyramidal symptoms (HR = 1.33, 95% CI = 1.08–1.64) or sexual dysfunction (HR = 1.59, 95% CI = 1.03–2.46). Among antipsychotics prescribed at any point during treatment, lurasidone (HR = 1.40, 95% CI = 1.10–1.78) and aripiprazole (HR = 1.09, 95% CI = 1.01–1.19) were associated with earlier discontinuation than olanzapine. Conversely, clozapine (HR = 0.55, 95% CI = 0.41–0.73) and paliperidone 1-monthly (PP1M) long-acting injectable (HR = 0.80, 95% CI = 0.68–0.94) were associated with later discontinuation. Unexpectedly, for antipsychotics prescribed at any stage of treatment, sedation (HR = 0.89, 95% CI = 0.81–0.97), weight gain (HR = 0.73, 95% CI = 0.64–0.83), and multiple side effects (HR = 0.83, 95% CI = 0.76–0.90) were associated with later discontinuation. Conclusion: Earlier treatment discontinuation associated with sexual or extrapyramidal side effects could be related to their rapid onset and poor tolerability. Later treatment discontinuation associated with clozapine and PP1M could be related to the relative efficacy of these treatments. These findings merit consideration when selecting antipsychotic therapy for people with FEP.
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spelling doaj.art-e50e66bb6bcf433682c42e7c912ca4c52023-12-15T21:06:06ZengSAGE PublishingTherapeutic Advances in Psychopharmacology2045-12612023-11-011310.1177/20451253231211575Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record dataRashmi PatelAimee BrinnJessica IrvingJaya ChaturvediShanmukha GudisevaChristoph U. CorrellPaolo Fusar-PoliPhilip McGuireBackground: Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear. Objectives: To investigate whether antipsychotic discontinuation is associated with the prescription of particular antipsychotics and particular adverse effects. Design: Retrospective cohort study. Methods: We assembled de-identified electronic health record (EHR) data from 2309 adults with FEP who received care from the South London and Maudsley NHS Foundation Trust between 1st April 2008 and 31st March 2019. Associations between antipsychotic medications, clinician-recorded side effects and treatment discontinuation were investigated across a mean follow-up period of 34.2 months using Cox regression. Results: The mean age of patients was 26.7 years and 1492 (64.6%) were male. Among first prescribed antipsychotic medications, discontinuation occurred earlier with haloperidol [hazard ratio (HR) = 2.78, 95% CI = 1.69–4.60] and quetiapine (HR = 1.43, 95% CI = 1.16–1.80) than with olanzapine. Discontinuation occurred sooner when there was evidence of extrapyramidal symptoms (HR = 1.33, 95% CI = 1.08–1.64) or sexual dysfunction (HR = 1.59, 95% CI = 1.03–2.46). Among antipsychotics prescribed at any point during treatment, lurasidone (HR = 1.40, 95% CI = 1.10–1.78) and aripiprazole (HR = 1.09, 95% CI = 1.01–1.19) were associated with earlier discontinuation than olanzapine. Conversely, clozapine (HR = 0.55, 95% CI = 0.41–0.73) and paliperidone 1-monthly (PP1M) long-acting injectable (HR = 0.80, 95% CI = 0.68–0.94) were associated with later discontinuation. Unexpectedly, for antipsychotics prescribed at any stage of treatment, sedation (HR = 0.89, 95% CI = 0.81–0.97), weight gain (HR = 0.73, 95% CI = 0.64–0.83), and multiple side effects (HR = 0.83, 95% CI = 0.76–0.90) were associated with later discontinuation. Conclusion: Earlier treatment discontinuation associated with sexual or extrapyramidal side effects could be related to their rapid onset and poor tolerability. Later treatment discontinuation associated with clozapine and PP1M could be related to the relative efficacy of these treatments. These findings merit consideration when selecting antipsychotic therapy for people with FEP.https://doi.org/10.1177/20451253231211575
spellingShingle Rashmi Patel
Aimee Brinn
Jessica Irving
Jaya Chaturvedi
Shanmukha Gudiseva
Christoph U. Correll
Paolo Fusar-Poli
Philip McGuire
Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data
Therapeutic Advances in Psychopharmacology
title Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data
title_full Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data
title_fullStr Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data
title_full_unstemmed Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data
title_short Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data
title_sort oral and long acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis a longitudinal analysis of electronic health record data
url https://doi.org/10.1177/20451253231211575
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