Thomas R. E. Barnes

Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review

BACKGROUNDnWhether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes.nnnMETHODSnWe searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate.nnnFINDINGSnThere was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1.41, 95% CI 1.20-1.65). Findings were consistent with a dose-response effect, with greater risk in people who used cannabis most frequently (2.09, 1.54-2.84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding effect was present for both psychotic and affective outcomes.nnnINTERPRETATIONnThe evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication effects, although evidence for affective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.

Effects of cannabis use on outcomes of psychotic disorders : systematic review

BACKGROUNDnIt is unclear if research findings support clinical opinion that cannabis use leads to worse outcomes in people with psychosis, or whether this impression is confounded by other factors.nnnAIMSnTo systematically review the evidence pertaining to whether cannabis affects outcome of psychotic disorders.nnnMETHODnWe searched 10 relevant databases (to November 2006), reference lists of included studies and contacted experts. We included 13 longitudinal studies from 15,303 references. Data extraction and quality assessment were conducted independently and in duplicate.nnnRESULTSnCannabis use was consistently associated with increased relapse and non-adherence. Associations with other outcome measures were more disparate. Few studies adjusted for baseline illness severity, and most made no adjustment for alcohol, or other potentially important confounders. Adjusting for even a few confounders often resulted in substantial attenuation of results.nnnCONCLUSIONSnConfidence that most associations reported were specifically due to cannabis is low. Despite clinical opinion, it remains important to establish whether cannabis is harmful, what outcomes are particularly susceptible, and how such effects are mediated. Studies to examine this further are eminently feasible.

A randomized controlled trial of cognitive-behavior therapy for persistent symptoms in schizophrenia: A five-year follow-up

Meta-analyses of randomized controlled trials support the efficacy of cognitive behavioral therapy (CBT) in the treatment of symptoms of schizophrenia refractory to antipsychotic medication. This article addresses the issue of medium term durability. A five-year follow-up was undertaken of a sample of 90 subjects who participated in a randomized controlled trial of CBT and befriending (BF). Patients received routine care throughout the trial and the follow-up period. Intention to treat multivariate analysis was performed by an independent statistician following multiple imputation of missing data. Fifty-nine out of ninety patients were followed up at 5 years (CBT=31, BF=28). In comparison to BF and usual treatment, CBT showed evidence of a significantly greater and more durable effect on overall symptom severity (NNT=10.36, CI -10.21, 10.51) and level of negative symptoms (NNT=5.22, CI -5.06 -5.37). No difference was found between CBT and BF on either overall symptoms of schizophrenia or depression. The initial cost of an adjunctive course of CBT for individuals with medication refractory schizophrenia may be justified in light of symptomatic benefits that persist over the medium term.

High-dose and combination antipsychotic prescribing in acute adult wards in the UK: the challenges posed by p.r.n. prescribing

BACKGROUNDnClinical guidelines recommend the routine use of a single antipsychotic drug in a standard dose, but prescriptions for high-dose and combined antipsychotics are common in clinical practice.nnnAIMSnTo evaluate the effectiveness of a quality improvement programme in reducing the prevalence of high-dose and combined antipsychotic prescribing in acute adult in-patient wards in the UK.nnnMETHODnBaseline audit was followed by feedback of benchmarked data and delivery of a range of bespoke change interventions, and then by a further audit 1 year later.nnnRESULTSnThirty-two services participated, submitting data for 3,942 patients at baseline and 3,271 patients at the 1-year audit. There was little change in the prevalence of high-dose (baseline 36%; re-audit 34%) or combined antipsychotic prescribing (baseline 43%; re-audit 39%). As required (p.r.n.) prescriptions were the principal cause of both high-dose and combined antipsychotic prescribing on both occasions.nnnCONCLUSIONSnThe quality improvement programme did not have a demonstrable impact on prescribing practice in the majority of services. Future efforts to align practice with clinical guidelines need to specifically target the culture and practice of p.r.n. prescribing.

Abnormal brain connectivity in first-episode psychosis: A diffusion MRI tractography study of the corpus callosum

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the clinical manifestations of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail and we present here a study of patients with first-episode psychosis using this technique. We selected the corpus callosum for this study because there is evidence that it is abnormal in schizophrenia. In addition, the topographical organization of its fibers makes it possible to relate focal abnormalities to specific cortical regions. Eighteen patients with first-episode psychosis and 21 healthy subjects took part in the study. A probabilistic tractography algorithm (PICo) was used to study fractional anisotropy (FA). Seed regions were placed in the genu and splenium to track fiber tracts traversing these regions, and a multi-threshold approach to study the probability of connection was used. Multiple linear regressions were used to explore group differences. FA, a measure of tract coherence, was reduced in tracts crossing the genu, and to a lesser degree the splenium, in patients compared with controls. FA was also lower in the genu in females across both groups, but there was no gender-by-group interaction. The FA reduction in patients may be due to aberrant myelination or axonal abnormalities, but the similar tract volumes in the two groups suggest that severe axonal loss is unlikely at this stage of the illness.

White matter tracts in first-episode psychosis: A DTI tractography study of the uncinate fasciculus

A model of disconnectivity involving abnormalities in the cortex and connecting white matter pathways may explain the symptoms and cognitive abnormalities of schizophrenia. Recently, diffusion imaging tractography has made it possible to study white matter pathways in detail, and we present here a study of patients with first-episode psychosis using this technique. We studied the uncinate fasciculus (UF), the largest white matter tract that connects the frontal and temporal lobes, two brain regions significantly implicated in schizophrenia. Nineteen patients with first-episode schizophrenia and 23 controls were studied using a probabilistic tractography algorithm (PICo). Fractional anisotropy (FA) and probability of connection were obtained for every voxel in the tract, and the group means and distributions of these variables were compared. The spread of the FA distribution in the upper tail, as measured by the squared coefficient of variance (SCV), was reduced in the left UF in the patient group, indicating that the number of voxels with high FA values was reduced in the core of the tract and suggesting the presence of changes in fibre alignment and tract coherence in the patient group. The SCV of FA was lower in females across both groups and there was no correlation between the SCV of FA and clinical ratings.

Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia

Background In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes. Aims To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point. Method Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later. Results There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition. Conclusions Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP.

Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis.

Objectives: To conduct a meta-analysis of randomized placebo-controlled trials (RCTs) of clozapine augmentation with another antipsychotic drug in patient with schizophrenia who partially respond to clozapine and compare the results with the findings of relevant open studies. Methods: A systematic literature search was conducted to identify eligible RCTs. All baseline, posttreatment, and change scores in these trials were included in the meta-analysis. For change in Brief Psychiatric Rating Scale/Positive and Negative Syndrome Scale total scores, the effect size was calculated, and for the proportion of patients with a reduction in Brief Psychiatric Rating Scale/Positive and Negative Syndrome Scale scores of 20% or more, the relative risk was calculated. Results: There was a total of 166 participants in the 4 eligible RCTs. Pooling effect sizes across these studies revealed clinically important heterogeneity (I2 = 63.5%). Analyzing by duration accounted for the heterogeneity (I2 = 0%), whereas analyzing by drug did not (I2 = 57.5%). The 2 RCTs lasting 10 weeks or more gave an odds ratio of response to treatment of 4.41 (95% confidence interval, 1.38 to 14.07). In 8 open studies identified, the same pattern of response was seen. The main treatment-emergent side effects reported were extrapyramidal side effects and raised serum prolactin. Conclusions: Augmentation of clozapine with another antipsychotic drug in patients with schizophrenic illness that has partially responded to clozapine is worthy of an individual clinical trial. This trial may need to be longer than the 4 to 6 weeks usually recommended for acute antipsychotic monotherapy.

Naturalistic follow-up of co-morbid substance use in schizophrenia: the West London first-episode study

Background The impact of co-morbid substance use in first-episode schizophrenia has not been fully explored. Method This naturalistic follow-up of a cohort of 152 people with first-episode schizophrenia examined substance use and clinical outcome in terms of symptoms and social and neuropsychological function. Results Data were collected on 85 (56%) of the patient cohort after a median period of 14 months. Over the follow-up period, the proportion of smokers rose from 60% at baseline to 64%. While 30% reported lifetime problem drinking of alcohol at baseline, only 15% had problem drinking at follow-up. Furthermore, while at baseline 63% reported lifetime cannabis use and 32% were currently using the drug, by the follow-up assessment the latter figure had fallen to 18.5%. At follow-up, persistent substance users had significantly more severe positive and depressive symptoms and greater overall severity of illness. A report of no lifetime substance use at baseline was associated with greater improvement in spatial working memory (SWM) at follow-up. Conclusions Past substance use may impede recovery of SWM performance in people with schizophrenia in the year or so following first presentation to psychiatric services. The prevalence of substance use other than tobacco tends to diminish over this period, in the absence of specific interventions. Persistent substance use in first-episode schizophrenia is associated with more severe positive and depressive symptoms but not negative symptoms, and should be a target for specific treatment intervention.

Screening for the metabolic syndrome in community psychiatric patients prescribed antipsychotics: a quality improvement programme

Objective:u2002 The aim was to evaluate a quality improvement programme designed to increase screening for the metabolic syndrome in community psychiatric patients prescribed antipsychotics.