Can the use of long-acting injectable antipsychotic preparations be increased in routine clinical practice and the benefits realised?

Background: The use of continuing antipsychotic medication is an established evidence-based strategy for preventing relapse in people with schizophrenia, but medication adherence is known to be suboptimal. Covert non-adherence can be eliminated by the use of long-acting injectable (LAI) formulations. We sought to (1) raise awareness among clinicians of the potential benefits of LAI antipsychotic formulations, (2) increase use of these formulations for the treatment of schizophrenia in routine clinical practice and thereby (3) reduce the number of relapses requiring hospitalisation in patients with schizophrenia under our care.

Attitudes of European physicians towards the use of long-acting injectable antipsychotics.

Background: Prescription rates for long-acting injectable (LAI) antipsychotic formulations remain relatively low in Europe despite improved adherence over alternative oral antipsychotic treatments. This apparent under-prescription of LAI antipsychotics may have multiple contributing factors, including negative mental health practitioner attitudes towards the use of LAIs.

Methods: The Antipsychotic Long acTing injection in schizOphrenia (ALTO) non-interventional study (NIS), conducted across several European countries, utilised a questionnaire that was specifically designed to address physicians' attitudes and beliefs towards the treatment of schizophrenia with LAI antipsychotics.

Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia.

Objective: The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.

Methods: A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms.

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.

Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder.

Baseline results from the European non-interventional Antipsychotic Long acTing injection in schizOphrenia (ALTO) study.

Background: The Antipsychotic Long-acTing injection in schizOphrenia (ALTO) study was a non-interventional study across several European countries examining prescription of long-acting injectable (LAI) antipsychotics to identify sociodemographic and clinical characteristics of patients receiving and physicians prescribing LAIs. ALTO was also the first large-scale study in Europe to report on the use of both first- or second-generation antipsychotic (FGA- or SGA-) LAIs.

Methods: Patients with schizophrenia receiving a FGA- or SGA-LAI were enrolled between June 2013 and July 2014 and categorized as incident or prevalent users.

Antipsychotic therapeutic drug monitoring: psychiatrists' attitudes and factors predicting likely future use.

Background: This study aimed to explore predictive factors for future use of therapeutic drug monitoring (TDM) and to further examine psychiatrists' current prescribing practices and perspectives regarding antipsychotic TDM using plasma concentrations.

Method: A cross-sectional study for consultant psychiatrists using a postal questionnaire was conducted in north-west England. Data were combined with those of a previous London-based study and principal axis factor analysis was conducted to identify predictors of future use of TDM.

Olanzapine and risperidone plasma concentration therapeutic drug monitoring: A feasibility study.

Background: This study aimed to develop a clinically acceptable method of therapeutic drug monitoring (TDM) for olanzapine and risperidone and to evaluate the feasibility of its implementation.

Method: A non-randomised study of inpatients from five Mental Health Trusts was conducted, with a clinical interview at the time of TDM and a subsequent 6-week follow-up review of clinical notes. The TDM intervention comprised: (a) a venous blood sample taken 12 hours post-dose, 7-10 days after drug initiation, and (b) rapid results feedback, with interpretation algorithm guidance.

The use of psychotropic medication in patients with emotionally unstable personality disorder under the care of UK mental health services.

Background: Guideline recommendations for the pharmacologic treatment of personality disorder lack consensus, particularly for emotionally unstable personality disorder (EUPD), and there is limited information on current prescribing practice in the United Kingdom.

Objective: To characterize the nature and quality of current prescribing practice for personality disorder across the United Kingdom, as part of a quality improvement program.

Method: A cross-sectional survey of self-selected psychiatric services providing care for adults with personality disorder (ICD-10 criteria) was conducted.

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method.

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence.

Assessment and treatment of physical health problems among people with schizophrenia: national cross-sectional study.

Background: In the UK and other high-income countries, life expectancy in people with schizophrenia is 20% lower than in the general population.

Aims: To examine the quality of assessment and treatment of physical health problems in people with schizophrenia. Method Retrospective audit of records of people with schizophrenia or schizoaffective disorder aged ⩾18.

Re-examining the role of benzodiazepines in the treatment of schizophrenia: a systematic review.

Background: Benzodiazepine prescribing for schizophrenia occurs in clinical practice and antipsychotic trials. This review examined the clinical outcomes for benzodiazepines in schizophrenia.

Method: A systematic search identified randomised controlled trials that evaluated benzodiazepines in comparison with placebo or antipsychotics, and also as adjuncts to antipsychotics.

Dose equivalents for second-generation antipsychotics: the minimum effective dose method.

Background: Clinicians need to know the right antipsychotic dose for optimized treatment, and the concept of dose equivalence is important for many clinical and scientific purposes.

Methods: We refined a method presented in 2003, which was based on the minimum effective doses found in fixed-dose studies. We operationalized the selection process, updated the original findings, and expanded them by systematically searching more recent literature and by including 13 second-generation antipsychotics.

Quality of prescribing for schizophrenia: evidence from a national audit in England and Wales.

The National Audit of Schizophrenia (NAS) examined the quality of care received in England and Wales. Part of the audit set out to determine whether six prescribing standards, set by the national clinical guidelines for schizophrenia, were being implemented and to prompt improvements in care. Mental Health Trusts and Health Boards provided data obtained from case-notes for adult patients living in the community with schizophrenia or schizoaffective disorder.

Psychiatrists' perspectives on antipsychotic dose and the role of plasma concentration therapeutic drug monitoring.

Background: Why psychiatrists choose a particular dose of antipsychotic for an individual patient with schizophrenia is unknown. This study aimed to investigate consultant psychiatrists' perspectives on the dose titration and their attitudes towards therapeutic drug monitoring (TDM) for antipsychotics.

Method: A cross-sectional quantitative questionnaire study of consultant psychiatrists based in London was conducted.

Plasma quetiapine in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 2000-2011.

Objective: Suggested predose plasma quetiapine target ranges for effective therapy in schizophrenia lie between 50 and 500 µg/l. We aimed to examine data from a quetiapine therapeutic drug monitoring (TDM) service to assess the plasma quetiapine concentrations attained at specified doses in clinical practice.

Method: We studied TDM data from patients given immediate-release quetiapine in the period 2000-2011.

The knowledge and attitudes of psychiatrists towards antipsychotic long-acting injections in Nigeria.

Background: Antipsychotic long-acting injections (LAIs) reduce covert nonadherence with medication in the clinical management of psychotic disorders. However, they are variably utilised by clinicians, especially in the long term. Factors including poor knowledge, stigma and perceived coercion can all adversely influence LAI utilisation.

How to compare doses of different antipsychotics: a systematic review of methods.

Background: The ability to calculate equivalent dosage is important when comparing or switching between doses of different antipsychotics in the treatment of schizophrenia. It is also necessary when designing antipsychotic comparator trials which control for dosage.

Method: A systematic review to identify and critically evaluate the methods available for the estimation of antipsychotic dose equivalence was conducted.

Naturalistic outcomes of community treatment orders: antipsychotic long-acting injections versus oral medication.

Background: Community treatment orders (CTOs) are initiated to compel the patient in the community to take part in a management plan, of which medication is often a part. CTOs were introduced in 2008, in England and Wales. We evaluated naturalistic outcomes of CTOs, according to the antipsychotic formulation prescribed at CTO initiation.

Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy, and response.

Objective: To conduct a systematic review examining the relationships between olanzapine dose, clinical outcome, dopamine occupancy, and plasma concentration; and to evaluate the potential for therapeutic drug monitoring.

Methods: A search using Embase, Medline, and Pubmed was conducted; and the literature was systematically reviewed. Studies meeting inclusion criteria were examined.

Clinician hesitation prior to clozapine initiation: is it justifiable?

Clozapine has been endorsed by national clinical guidelines for 10 years and yet underutilisation and delay to initiation remain rife. Although there will be good clinical reasons for clozapine not being initiated for some patients, it is hypothesised here that for others, clinicians' attitudes and preferences are the most likely predictive factors.

Plasma amisulpride in relation to prescribed dose, clozapine augmentation, and other factors: data from a therapeutic drug monitoring service, 2002-2010.

Objective: This study aimed to investigate the effect of dose and other factors on plasma amisulpride concentrations in clinical practice.

Method: Amisulpride therapeutic drug monitoring data 2002-2010 have been studied.

Results: There were 296 samples (196 adult patients).

Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged <18 years: data from a therapeutic drug monitoring service, 1994-2010.

Aim: Clozapine is used in children and adolescents to treat early onset schizophrenia, but data on efficacy and on the plasma clozapine concentrations attained are limited.

Methods: We studied data from a clozapine therapeutic drug monitoring (TDM) service, patients in the UK and Eire aged <18 years, 1994-2010. Multiple linear regression analysis was performed to investigate the relationship between plasma clozapine concentration and dose, age, sex, body weight, plasma clozapine:norclozapine ratio (clozapine metabolic ratio (MR)) and smoking habit.

Risperidone and total 9-hydroxyrisperidone in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 2002-2010.

Background: Information on the plasma risperidone and total 9-hydroxyrisperidone concentrations ('total risperidone') attained in clinical practice is scant. The aim of this work was to gather such information to better inform the interpretation of results.

Method: This involved the audit of plasma total risperidone data from a risperidone therapeutic drug monitoring service 2002-2010.