Timing of antipsychotics and benzodiazepine initiation during a first episode of psychosis impacts clinical outcomes: Electronic health record cohort study

Abstract

The impact of timing of antipsychotics and benzodiazepine treatment during a first episode of psychosis on clinical outcomes is unknown. We present a RECORD-compliant electronic health record cohort study including patients (n = 4,483, aged 14–35) with a primary diagnosis of any non-organic ICD-10 first episode of psychosis at SLAM-NHS between 2007 and 2017. The impact of antipsychotic timing (prescription > 1 week after a first episode of psychosis) was assessed on the primary outcome (risk of any psychiatric inpatient admission over 6 years), and secondary outcomes (cumulative duration of any psychiatric/medical/accident/emergency [A&E] admission over 6 years). The impact of prescribing benzodiazepine before antipsychotic at any point and of treatment patterns (antipsychotic alone, benzodiazepine alone, combination of antipsychotic with benzodiazepine) within the first week after a first episode of psychosis were also assessed. Survival analyses and zero-inflated negative binomial regressions, adjusted for core covariates, and complementary analyses were employed. Antipsychotic prescribed >1 week after a first episode of psychosis did not affect the risk of any psychiatric admission (HR = 1.04, 95% CI = 0.92–1.17, p = 0.557), but increased the duration of any psychiatric (22–28%), medical (78–35%) and A&E (30–34%) admission (months 12–72). Prescribing benzodiazepine before antipsychotic at any point did not affect the risk of any psychiatric admission (HR = 1.03, 95% CI = 0.94–1.13, p = 0.535), but reduced the duration of any psychiatric admission (17–24%, months 12–72), and increased the duration of medical (71–45%, months 12–72) and A&E (26–18%, months 12–36) admission. Prescribing antipsychotic combined with benzodiazepine within the first week after a first episode of psychosis showed better overall clinical outcomes than antipsychotic or benzodiazepine alone. Overall, delaying antipsychotic 1 week after a first episode of psychosis may worsen some clinical outcomes. Early benzodiazepine treatment can be considered with concomitant antipsychotic but not as standalone intervention.

Longitudinal evolution of the transdiagnostic prodrome to severe mental disorders: a dynamic temporal network analysis informed by natural language processing and electronic health records

“…Furthermore, we found minimal differences among diagnosis-specific subnetworks, highlighting substantial overlap in the dynamic progression of prodromal stages of UMD, BMD and PSY. This finding aligns with previous findings of transdiagnostic overlap in duration, first presentation and frequencies of prodromal features across SMD, 29 and extends them by showing transdiagnostic temporal and causal relationships between these features. These findings support the emergence of transdiagnostic early detection strategies that have previously been conceptualised in the clinical staging model [30][31][32][33][34] and the Clinical High At Risk Mental State (CHARMS 35 ) criteria, which have started to be implemented clinically.…”

“…Similarly, assessments to detect individuals at clinical high risk for psychosis (CHR-P) have low specificity 47 and may be improved through additional features from our analyses. Echoing our earlier findings, 29 PSY exhibited the most distinctive pattern of relationships between prodromal features, with stronger connections compared to both UMD and BMD in symptom pairs relating to hallucinations, paranoia, tobacco use and disturbed sleep. The prominence of positive symptoms in PSY affirms the relevance of these assessments, [48][49][50] which primarily consider these symptoms.…”

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis

“…Additionally, in our sensitivity analyses, there was a trending increased risk of subsequent A&E attendance by BDZ exposure when analysis was restricted to antipsychotic-naïve individuals, and a significant increased risk on A&E attendance when BDZ exposures from a non-benzodiazepine hypnotic were removed from analysis. Whilst this is the first study to examine the influence of BDZ exposure on clinical outcomes in CHR-P individuals, a recent EHR study in first-episode psychosis patients investigated the effects of antipsychotic and BDZ treatment (within the first week of illness onset) on clinical outcomes and found similar effects 35 . BDZ treatment prior to antipsychotic treatment (vs. after) increased the duration of medical and A&E admission in first-episode patients, whilst reducing the length of psychiatric admission 35 .…”

“…Whilst this is the first study to examine the influence of BDZ exposure on clinical outcomes in CHR-P individuals, a recent EHR study in first-episode psychosis patients investigated the effects of antipsychotic and BDZ treatment (within the first week of illness onset) on clinical outcomes and found similar effects 35 . BDZ treatment prior to antipsychotic treatment (vs. after) increased the duration of medical and A&E admission in first-episode patients, whilst reducing the length of psychiatric admission 35 . Furthermore, increased readmission to hospital has been associated with BDZ exposure in patients with chronic schizophrenia 36,37 .…”

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis

“…Given that recent studies indicated a modulating effect of BDZ on outcomes in first-episode psychosis (Arribas, Solmi, Thompson, Oliver, & Fusar-Poli, 2022) as well as in schizophrenia (Strømme et al, 2022), the current meta-analytical study was designed to address the specific question whether baseline exposure to BDZ in CHR-P individuals impacts the longitudinal risk of transition to psychosis. (For a succinct overview of the role of anxiety and anti-anxiety treatment in CHR-P, please see 'Integrative appendix 2' in online Supplementary materials).…”