Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology.

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

Sodium valproate in psychiatric practice: time for a change in perception.

Sodium valproate and related preparations have recently undergone regulatory review following concern about effects on the unborn child and doctors' failure to communicate risk. The issues are wider. Valproate is overused in psychiatry based on the false perception that 'ease' of use equates to better safety than alternatives. Valproic acid can disrupt fundamental physiological processes, the consequences of which are poorly understood and little discussed in the psychiatric literature. Valproate may be useful in a small number of patients with bipolar disorder but current prescribing patterns are unjustified. Perception needs to change. DECLARATION OF INTEREST: D.C.O. is psychiatric commissioner on the Commission on Human Medicines and a member of the European Medicines Agency's Scientific Advisory Group on Psychiatry. He chaired the European Medicines Agency's review of the psychiatric use of valproate in pregnancy and women of childbearing potential.

Duration of untreated illness and outcome in schizophrenia: test of predictions in relation to relapse risk.

BACKGROUND: The nature of the relationship between duration of the pre-diagnostic interval in schizophrenia and better outcomes remains unclear. AIMS: To re-examine data from one of the earliest studies suggesting an association between long pre-treatment interval and compromised outcome, assessing the relationship between symptomatic and social variables and increased relapse risk at 1 year. METHOD: Symptomatic, social and demographic data from participants in the Northwick Park Study of First Episodes who completed 12-month follow-up (n = 101) were re-analysed in the context of duration of untreated illness (DUI). RESULTS: At admission, those with long DUI were more likely to have lower scores on tension derived from the Present State Examination, exhibited more behaviour threatening to others and more bizarre behaviour, were more likely to be single, to live alone or dependently, to be unemployed and to have experienced more adverse life events prior to admission. Logistic regression showed that diminished tension, bizarre behaviour and unemployed status independently increased the risk of relapse, bizarre behaviour making the single biggest contribution. Tension did not remain significant with log-transformation of data. CONCLUSIONS: Findings are consistent with the conclusion that long DUI can reflect characteristics of the psychosis itself rather than delay in treatment.

Progressive temporal lobe grey matter loss in adolescents with schizotypal traits and mild intellectual impairment.

Adolescents with mild intellectual impairment are known to have an increased risk of schizophrenia compared to the general population. However, little is known regarding the association between potential risk markers for later schizophrenia within this population. We therefore set out to examine the association between schizotypal traits and progressive grey matter loss in adolescents with mild intellectual impairment. Ninety-eight adolescents receiving educational assistance were divided into two groups based on their degree of schizotypal features, measured using the Structured Interview for Schizotypy (SIS). Each participant received two structural magnetic resonance imaging scans approximately 16 months apart. Changes over time in the voxel-wise presentation of tissue were evaluated using tensor based morphometry. Those with marked schizotypal features exhibited significantly greater grey matter losses in the left medial temporal lobe than those without. Three focal locations were identified, two within the left amygdala and one in the left parahippocampal gyrus. Thus, adolescents with cognitive impairment and schizotypal features show changes in brain structure over time, changes that are consistent with those identified in other high risk populations. Medial temporal grey matter loss may therefore represent a common neuroanatomical substrate of risk for schizophrenia, common to familial, prodromal and cognitive high risk groups.

What CATIE did: some thoughts on implications deep and wide.

The author discusses five lessons that can be learned from the seminal results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The lessons extend beyond practice implications to fundamental questions about how psychopharmacology studies are conducted and how results are interpreted and given relevance in regard to prescribing. The author recounts the history of the term "atypical" and how it came to be understood in the context of antipsychotics. The error of using high-dose haloperidol as a comparator in assessments of new antipsychotics -- and of generalizing from the results of these studies -- is also discussed. The CATIE results force uncomfortable questions about the extent of knowledge concerning the clinical pharmacology of a major treatment modality, which the author illustrates by examining possible reasons for the differential clinical actions of clozapine. The author concludes that CATIE benefited both patients and clinicians by opening up to patients the full gamut of antipsychotics for treatment planning and by reinstating to physicians their key skill in expert, individualized prescribing.