The association of comorbid substance use disorders on time to treatment discontinuation in patients with schizophrenia

Rashmi Patel, Emily OC Palmer, Kelly MY Chan, Matthew Valko, Guruprabha Guruswamy, Sheryl Ker, Gunjan Batra, Scott H. Kollins, Miguel E Rentería

Research output: Contribution to journalMeeting abstractpeer-review


Background: Around 42% of patients with schizophrenia have a comorbid diagnosis of substance use disorder (SUD). [1] Patients with schizophrenia and comorbid SUDs are at increased risk of poor clinical outcomes.[2] Time until the first discontinuation of antipsychotic treatment may provide an indication of the effectiveness, safety, and tolerability of treatment.[3] This study aimed to assess the associations between comorbid SUDs in patients with schizophrenia and the time until the first discontinuation of antipsychotic treatment.

Method: An observational retrospective study was conducted using de-identified electronic health record (EHR) data from 25 US mental health services analysed using the NeuroBlu platform.[4] A total of 13,634 adults with a diagnosis of schizophrenia (ICD-10 F20*) before January 2019 were included in the cohort. Patients were divided into two groups, “with-SUD”, and “without-SUD,” depending on whether there was a record of SUD diagnosis before or at the same time as their schizophrenia diagnosis. Details of the specific type of SUD were also captured. The index date was defined as the initial date of a schizophrenia diagnosis. Time to antipsychotic discontinuation was measured as the number of days from first antipsychotic prescription to discontinuation. If the prescription was changed and the timeline overlapped or had a gap of fewer than 30 days, this was considered a single prescription duration. Mann Whitney U analysis was used to compare group differences. A Cox proportional hazard (CoxPH) model was used to assess the association of specific SUD comorbidities and the duration of time to first antipsychotic discontinuation. Age, gender, race, marital status, and employment status were included as covariates.

Results: The time to first antipsychotic discontinuation was shorter in patients in the with-SUD group (Mean (SD) 176.8 (393.3) days) compared with the without-SUD group (Mean (SD) 270.0 (538.1) days) (U = 1.44e7, p
Conclusion: Patients with schizophrenia and certain comorbid SUDs are at increased risk of antipsychotic treatment discontinuation compared to those without a comorbid SUD diagnosis. This may reflect a reduced response to antipsychotic treatment, high side effect burden or poorer treatment adherence.[5] It is currently unclear to what extent this treatment failure may contribute to poorer clinical outcomes for this patient group. Our results suggest that patients with schizophrenia and comorbid SUDs may benefit from specialized dual-diagnosis treatment programmes that treat both schizophrenia and comorbid SUD.

1.Hunt, G.E., et al., Prevalence of comorbid substance use in schizophrenia spectrum disorders in community and clinical settings, 1990–2017: Systematic review and meta-analysis. Drug and Alcohol Dependence, 2018. 191: p. 234-258. 2.Kessler, T. and S. Lev-Ran, The association between comorbid psychiatric diagnoses and hospitalization-related factors among individuals with schizophrenia. Compr Psychiatry, 2019. 89: p. 7-15. 3.Ascher-Svanum, H., et al., Reasons for discontinuation and continuation of antipsychotics in the treatment of schizophrenia from patient and clinician perspectives. Current Medical Research and Opinion, 2010. 26(10): p. 2403-2410. 4.Patel, R., et al., NeuroBlu, an electronic health record (EHR) trusted research environment (TRE) to support mental healthcare analytics with real-world data. BMJ Open, 2022. 12(4): p. e057227. 5.Liu-Seifert, H., D.H. Adams, and B.J. Kinon, Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs. BMC Medicine, 2005. 3(1).
Original languageEnglish
Article number100555
Pages (from-to)227
Number of pages228
JournalNeuroscience Applied
Issue numberS2
Publication statusPublished - 24 Dec 2022


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