Natalia Petros

Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study

BACKGROUND Although cannabis use after a first episode of psychosis has been associated with relapse, little is known about the determinants of this most preventable risk factor for relapse of psychosis. Here we aimed to study whether the effects on outcome vary depending on the type of cannabis consumed and usage pattern. METHODS In this observational study, we prospectively recruited and followed up patients aged 18-65 years who presented with their first episode of psychosis to psychiatric services in south London, London, UK. Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital. We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis, potency of cannabis consumed, and frequency of use after the onset of their illness. We used multiple regression analyses (logistic or binominal) to compare the different cannabis use groups and propensity score analysis to validate the results. FINDINGS Between April 12, 2002, and July 26, 2013, 256 patients presented with a first episode of psychosis. We did follow-up assessments for these patients until September, 2015. Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse. In multiple analysis, continued high-frequency users (ie, daily use in all 24 months) of high-potency (skunk-like) cannabis had the worst outcome, indexed as an increased risk for a subsequent relapse (odds ratio [OR] 3·28; 95% CI 1·22-9·18), more relapses (incidence rate ratio 1·77; 95% CI 0·96-3·25), fewer months until a relapse occurred (b -0·22; 95% CI -0·40 to -0·04), and more intense psychiatric care (OR 3·16; 95% CI 1·26-8·09) after the onset of psychosis. INTERPRETATION Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis. FUNDING National Institute for Health Research (NIHR).

Association Between Continued Cannabis Use and Risk of Relapse in First-Episode Psychosis: A Quasi-Experimental Investigation Within an Observational Study

Importance Cannabis use after first-episode psychosis is associated with poor outcomes, but the causal nature of this association is unclear. Objective To examine the precise nature of the association between continued cannabis use after the onset of psychosis and risk of relapse of psychosis. Design, Setting, and Participants This prospective cohort study followed up for at least 2 years after the onset of psychosis 220 patients who presented to psychiatric services in South London, England, from April 12, 2002, to July 26, 2013, with first-episode psychosis. Longitudinal modeling (fixed-effects analysis, cross-lagged path analysis) was used to examine whether the association between changes in cannabis use and risk of relapse over time is the result of shared vulnerability between psychosis and cannabis use, psychosis increasing the risk of cannabis use (reverse causation), or a causal effect of cannabis use on psychosis relapse. Interventions Exposure to cannabis within the first and second years after onset of psychosis. Main Outcomes and Measures The main outcome measure was relapse of psychosis, defined as subsequent hospitalization for psychosis. Effect of cannabis use status in the first year (Ct1) and second year (Ct2) and pattern of cannabis use continuation in the first year and second year were modeled for risk of relapse in the first year (Rt1) and risk of relapse in the second year (Rt2) after psychosis onset. Results A total of 220 patients with first-episode psychosis were included in the analysis (mean [SD] age, 28.62 [8.58] years; age range, 18-65 years; 90 women [40.9%] and 130 men [59.1%]). Fixed-effects models that adjusted for time-variant (other illicit drug use, antipsychotic medication adherence) and time-invariant (eg, genetic or premorbid environment) unobserved confounders revealed that there was an increase in the odds of experiencing a relapse of psychosis during periods of cannabis use relative to periods of no use (odds ratio, 1.13; 95% CI, 1.03-1.24). Change in the pattern of continuation significantly increased the risk (odds ratio, 1.07; 95% CI, 1.02-1.13), suggesting a dose-dependent association. Cross-lagged analysis confirmed that this association reflected an effect of cannabis use on subsequent risk of relapse (Ct1→Rt2: β = 0.44, P = .04) rather than an effect of relapse on subsequent cannabis use (Rt1→Ct2: β = -0.29, P = .59). Conclusions and Relevance These results reveal a dose-dependent association between change in cannabis use and relapse of psychosis that is unlikely to be a result of self-medication or genetic and environmental confounding.

Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first-episode psychosis: a prospective analysis

Summary Background Cannabis use following the onset of first-episode psychosis has been linked to both increased risk of relapse and non-adherence with antipsychotic medication. Whether poor outcome associated with cannabis use is mediated through an adverse effect of cannabis on medication adherence is unclear. Methods In a prospective analysis of data acquired from four different adult inpatient and outpatient units of the South London and Maudsley Mental Health National Health Service Foundation Trust in London, UK, 245 patients were followed up for 2 years from the onset of first-episode psychosis. Cannabis use after onset of psychosis was assessed by self-reports in face-to-face follow-up interviews. Relapse data were collected from clinical notes using the WHO Life Chart Schedule. This measure was also used to assess medication adherence on the basis of both face-to-face interviews and clinical notes. Patients were included if they had a diagnosis of first-episode non-organic or affective psychosis according to ICD-10 criteria, and were aged between 18 and 65 years when referred to local psychiatric services. We used structural equation modelling analysis to estimate whether medication adherence partly mediated the effects of continued cannabis use on risk of relapse. The primary outcome variable was relapse, defined as admission to a psychiatric inpatient unit after exacerbation of symptoms within 2 years of first presentation to psychiatric services. Information on cannabis use over the first 2 years after onset of psychosis was investigated as a predictor variable for relapse. Medication adherence was assessed as a mediator variable on the basis of clinical records and self-report data. Study researchers (TS, NP, EK, and EF) rated the adherence. Findings 397 patients who presented with their first episode of psychosis between April 12, 2002, and July 26, 2013 had a follow-up assessment until September, 2015. Of the 397 patients approached for followed up, 133 refused to take part in this study and 19 could not be included because of missing data. 91 (37%) of 245 patients with first-episode psychosis had a relapse over the 2 years of follow-up. Continued cannabis use predicted poor outcome, including risk of relapse, number of relapses, length of relapse, and care intensity at follow-up. In controlled structural equation modelling analyses, medication adherence partly mediated the effect of continued cannabis use on outcome, including risk of relapse (proportion mediated=26%, βindirect effects=0·08, 95% CI 0·004 to 0·16), number of relapses (36%, βindirect effects=0·07, 0·003 to 0·14), time until relapse (28%, βindirect effects=–0·26, −0·53 to 0·001) and care intensity (20%, βindirect effects=0·06, 0·004 to 0·11) but not length of relapse (6%, βindirect effects=0·03, −0·03 to 0·09). The adjusted models explained moderate amounts of variance for outcomes defined as risk of relapse (R2=0·25), number of relapses (R2=0·21), length of relapse (R2=0·07), time until relapse (R2=0·08), and care intensity index (R2=0·15). Interpretation Between 20% and 36% of the adverse effects of continued cannabis use on outcome in psychosis might be mediated through the effects of cannabis use on medication adherence. Interventions directed at medication adherence could partly help mitigate the harm from cannabis use in psychosis. Funding This study is funded by the National Institute of Health Research (NIHR) Clinician Scientist award.

Effect of continued cannabis use on medication adherence in the first two years following onset of psychosis

Uncertainty exists whether the use of non-prescription psychoactive substances following onset of a first episode of psychosis (FEP), in particular cannabis use, affects medication adherence. Data from FEP patients (N=233) obtained through prospective assessments measured medication adherence and pattern of cannabis and other substance use in the first two years following onset of psychosis. Multiple logistic regression analyses were employed to compare the different substance use groups with regard to risk of medication non-adherence, while controlling for confounders. The proportion of non-adherent patients was higher in those who continued using high-potency forms of cannabis (skunk-like) following the onset (83%) when compared to never regular users (51%), corresponding to an Odds Ratio (OR) of 5.26[95% Confidence Interval (CI) 1.91-15.68]. No significant increases in risk were present in those who used cannabis more sporadically or used milder forms of cannabis (hash-like). Other substances did not make an independent contribution in this model, including cigarette use ([OR 0.88, 95% CI 0.41-1.89]), alcohol use ([OR 0.66, 95% CI 0.27-1.64]) or regular use of other illicit drugs ([OR 1.03, 95% CI 0.34-3.15]) following the onset. These results suggest that continued use of high-potency cannabis following the onset of psychosis may adversely affect medication adherence.

Impact of childhood trauma on risk of relapse requiring psychiatric hospital admission for psychosis

Relapse in psychosis typically necessitates admission to hospital placing a significant financial burden on the health service. Exposure to childhood trauma is associated with an increased risk of psychosis, however, the extent to which this influences relapse is unclear. This report summarises current research investigating the influence of childhood trauma on relapse requiring psychiatric hospital admission for psychosis. Seven studies were included; two revealed a positive association between childhood trauma and relapse admission, two studies found a negative relationship and three found no significant difference. Inconsistent current evidence suggests a need for further research in this area.