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Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study.

ABSTRACT: OBJECTIVE:To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP). DESIGN:Observational study with exploratory mediation analysis. SETTING:Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust. PARTICIPANTS:2026 people presenting to early intervention services with FEP. EXPOSURE:Cannabis use at presentation, identified using natural language processing. MAIN OUTCOME MEASURES:admission to psychiatric hospital and clozapine prescription up to 5 years following presentation. MEDIATOR:Number of unique antipsychotics prescribed. RESULTS:Cannabis use was present in 46.3% of the sample at first presentation and was particularly common in patients who were 16-25, male and single. It was associated with increased frequency of hospital admission (incidence rate ratio 1.50, 95% CI 1.25 to 1.80), increased likelihood of compulsory admission (OR 1.55, 1.16 to 2.08) and greater number of days spent in hospital (β coefficient 35.1 days, 12.1 to 58.1). The number of unique antipsychotics prescribed, mediated increased frequency of hospital admission (natural indirect effect 1.09, 95% CI 1.01 to 1.18; total effect 1.50, 1.21 to 1.87), increased likelihood of compulsory admission (natural indirect effect (NIE) 1.27, 1.03 to 1.58; total effect (TE) 1.76, 0.81 to 3.84) and greater number of days spent in hospital (NIE 17.9, 2.4 to 33.4; TE 34.8, 11.6 to 58.1). CONCLUSIONS:Cannabis use in patients with FEP was associated with an increased likelihood of hospital admission. This was linked to the prescription of several different antipsychotic drugs, indicating clinical judgement of antipsychotic treatment failure. Together, this suggests that cannabis use might be associated with worse clinical outcomes in psychosis by contributing towards failure of antipsychotic treatment.

SUBMITTER: Patel R

PROVIDER: S-EPMC4785290 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study.

Patel Rashmi R Wilson Robin R Jackson Richard R Ball Michael M Shetty Hitesh H Broadbent Matthew M Stewart Robert R McGuire Philip P Bhattacharyya Sagnik S

BMJ open 20160303 3

<h4>Objective</h4>To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP).<h4>Design</h4>Observational study with exploratory mediation analysis.<h4>Setting</h4>Anonymised electronic mental health record data from the South London and ...[more]

PMID: 26940105

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Project description:BackgroundThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated.MethodsUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsPerceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.ConclusionsThese findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain-behavior relationships vary as a function of development.

Project description:ImportanceDuration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known.ObjectivesTo determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP.Design, setting, and participantsA naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex-matched healthy controls were recruited. After approximately 8 weeks, 31 participants with FEP and 32 controls were reassessed.ExposuresThe participants with FEP were treated according to standard clinical practice with second-generation antipsychotics.Main outcomes and measuresHippocampal volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in a standardized hippocampal volume of interest), DUP, 13 peripheral molecular biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were determined.ResultsThe full sample consisted of 71 individuals with FEP (39 women and 32 men; mean [SD] age, 25.2 [7.7] years) and 73 healthy controls (40 women and 33 men; mean [SD] age, 23.9 [6.4] years). Baseline median left HVI was lower in the FEP group (n?=?57) compared with the controls (n?=?54) (0.9275 vs 0.9512; difference in point estimate, -0.020 [95% CI, -0.029 to -0.010]; P?=?.001). During approximately 8 weeks of antipsychotic treatment, left HVI decreased in 24 participants with FEP at a median annualized rate of -.03791 (-4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13% annualized change from baseline) in 31 controls (difference in point estimate, -0.0424 [95% CI, -0.0707 to -0.0164]; P?=?.001). The change in left HVI was inversely associated with DUP (r?=?-0.61; P?=?.002). Similar results were found for right HVI, although the association between change in right HVI and DUP did not achieve statistical significance (r?=?-0.35; P?=?.10). Exploratory analyses restricted to the left HVI revealed an association between left HVI and markers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury, and markers reflecting dopaminergic and glutamatergic transmission.Conclusions and relevanceAn association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.

Project description:ObjectiveGuidelines for antipsychotic use in first-episode psychosis (FEP) recommend that medication be chosen initially on the basis of side effect profile with doses at the lower end of the range. Our objective was to describe the pattern of antipsychotic use in FEP over a period of 21 years in the context of changing clinical guidelines and the development of specialist early intervention in psychosis (EIP) services.SettingA community-based mental health service in South County Dublin (population 187 000) and a large private hospital.ParticipantsParticipants included 465 patients with FEP (146 from an epidemiological study (1995-1999) and 319 from a specialist EIP service (2005-2016)). Treatment with antipsychotic medication did not exceed 30 days at study entry.Outcome measuresThis is a descriptive study of prescribing practices in the context of service development and changing guidelines.ResultsFirst-generation antipsychotics were prescribed for 65% of the early cohort compared with 4.3% of the EIP cohort. Olanzapine was initially prescribed for 79.7% of EIP patients. Initial doses of medication were frequently low (≤50% British National Formulary (BNF) maximum) in both cohorts (71% and 78.6%). The demographic and clinical factors investigated did not influence the initial choice of antipsychotic medication significantly. Univariate logistic regression analysis suggested inpatient treatment setting was associated with a higher initial dose (>50% BNF maximum) of antipsychotic medication. Increasing dose requirements over the first month of engagement with an EIP service was associated with poorer global functioning at baseline, greater positive symptoms at baseline and the inpatient treatment setting. However, these associations were not seen in the multivariable model.ConclusionsSecond-generation antipsychotic prescribing predominates, but guidelines are often overlooked when choosing olanzapine notwithstanding lower initial dosages. EIP services should include proactive support for optimising medicines in line with evidence-based guidelines.

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Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study.

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Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study.

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