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Second generation antipsychotic long-acting injections have a greater cost than older depots. Their cost-effectiveness has yet to be established. We conducted a non-interventional, observational, follow-up of patients prescribed aripiprazole long-acting injection in two centres using a mirror image method. Data were available for 160 patients consecutively prescribed aripiprazole long-acting injection, of whom 30 were not included in the analysis (21 forensic patients, five incomplete data and four lost to follow-up). Of the 130 patients, 66 (51%) remained on aripiprazole long-acting injection at one year. The mean number of bed days in the year following aripiprazole long-acting injection initiation reduced to 22.82/patient (standard deviation [SD]=55.07) from 30.09/patient/year (SD=30.40) over the three years before initiation ( p

Our aim was to determine factors relating to continuation with treatment with paliperidone palmitate long-acting injection (PP) in a 2 year, non-interventional, observational study of the use of PP in consecutive patients treated in a secondary care environment. We followed-up 300 consecutive patients; 24 (8%) were lost to follow-up (7 deceased and 17 left the care of the trust). Overall, 107 patients of the remaining 276 who were not lost to follow-up (38.7%) completed 2 years’ continuous treatment. A further 21 (7.6%) patients discontinued PP but restarted it after >2 months, 11 (4.0%) of whom were still receiving PP at 2 years. Median treatment time for PP was 465 days (95% CI 333, 583 days). Prior treatment with risperidone reduced the risk of discontinuation by 39% (RR 0.61 (95% CI −0.44, 0.86, p=0.004)); being initiated as an out-patient by 49% (RR 0.51 (95% CI 0.36, 0.73 p=0.001)). Risk of discontinuation was increased by 63% when the reason for prescribing PP was poor tolerability of prior treatment (RR 1.63 (95% CI 1.05, 2.51 p=0.028)). The rate of continuation with PP at 2 years was higher than that seen with other long acting depot formulations. Likelihood of continuation can be vastly improved by targeting PP for those most likely to benefit.

BackgroundClinical trial outcomes are heavily influenced by the non-naturalistic clinical trial process. Observations of outcomes in clinical practice are a valuable adjunct to clinical trial results.HypothesisOur null hypothesis was that clinically indicated switching to paliperidone palmitate had no effect on hospital admissions or hospital bed days.MethodThis was a part-prospective mirror image study examining outcomes 2 years before starting paliperidone palmitate and 2 years after. Sensitivity analyses examined the effect of different placings of the mirror in the mirror image design.ResultsWe prospectively followed-up 225 patients prescribed paliperidone palmitate in clinical practice. At 2 years, 41.8% of patients were still receiving paliperidone palmitate. In the primary analysis, the mean number of admissions fell from 1.80 in the two years before starting paliperidone palmitate to 0.81 in two years following the drug’s initiation (outpatients) or two years following hospital discharge (inpatients) (P < 0.001). More than half of patients were not admitted to hospital during two years follow-up. Mean total bed days was reduced from 79.6 in the two years before to 46.2 in the two years after paliperidone palmitate initiation or discharge (P < 0.001). Sensitivity analyses gave broadly similar outcomes. Continuers demonstrated better outcomes than discontinuers in sensitivity analyses but not in the primary analysis.ConclusionPaliperidone palmitate initiation is associated with a substantial reduction in hospital admissions and days spent in hospital. The reduction in costs associated with reduced use of health care facilities is likely to exceed the purchase and administration costs of the drug.

Objective To assess the relationships among quetiapine blood concentration, daily dose, dopamine receptor occupancy, and clinical outcome in order, if possible, to define a target plasma level range in which therapeutic response is enhanced and adverse events are minimized. Data sources A search of the database Embase from 1974 to March 2009 and the databases MEDLINE and PubMed from 1966 to March 2009 was conducted. The drug name quetiapine was searched with each of the terms plasma levels, plasma concentration, therapeutic drug monitoring, and dopamine occupancy. Study selection The search uncovered 42 relevant articles. All published reports of quetiapine plasma or serum concentration were considered for inclusion if reported in relation to a dose, clinical outcome, or dopamine occupancy. After application of exclusion criteria, 20 articles remained. Data extraction Trials designed primarily to investigate an interaction between quetiapine and another medication were excluded, as were those designed to compare methods of blood sample analysis. Data synthesis There was a weak correlation between quetiapine dose and measured plasma concentration (from trough samples). Quetiapine dose was correlated with central dopamine D(2) occupancy, although the relationship between plasma level and D(2) occupancy is less clear. Conclusions The dose-response relationship for (immediate-release) quetiapine is established. Data on plasma concentration-response relationships are not sufficiently robust to allow determination of a therapeutic plasma level range for quetiapine. Therapeutic drug monitoring procedures are thus probably not routinely useful in optimizing quetiapine dose. Further examination of the relationship between peak quetiapine plasma concentration and clinical response is necessary.

To evaluate naturalistic use of risperidone long-acting injection (RLAI) and its effect on healthcare resource use.Mirror-image comparison of healthcare resource use for 3 years before RLAI initiation and 3 years after.In total, 211 of 277 patients consecutively prescribed RLAI were evaluable over the full 6-year study period. Median days in hospital/patient increased significantly in the 3 years after RLAI initiation [87 days (inter-quartile range 25-236) before vs. 192 days (47-426) after; P0.001]. Those 34 patients who continued RLAI for 3 years showed no change in median bed days [64 days (6.5-182) before vs. 64 days (12-180) after] and median number of admissions was decreased [1.5 (1-2.25) before vs. 1.00 (0-1.25) after; P = 0.001]. Healthcare costs more than doubled for the whole cohort (P0.001) and discontinuers (P0.001) and increased significantly for continuers (P = 0.010).RLAI did not decrease either time spent in hospital or overall healthcare costs in this patient cohort.

Objective: To evaluate the relationships between dose, plasma concentration, pharmacological activity and clinical outcome to evaluate the appropriateness of therapeutic drug monitoring (TDM) in patients receiving amisulpride. Method: Literature search of Embase, Medline and PubMed databases. Results: Amisulpride plasma concentration is closely correlated with dose (r2 = 0.96, P

To evaluate outcomes of clinical use of risperidone long-acting injection (RLAI) and determine factors predicting continuation with treatment.This prospective, 3-year follow-up of consecutive patients started on treatment with RLAI in normal clinical practice between August 2002 and September 2003 obtained demographic and clinical data from case notes, prescription charts, and hospital computer records. To determine predictors of continuation, a proportional hazards regression (Cox) model was constructed.The study included 211 evaluable patients. Over 3 years, 84% of subjects discontinued RLAI; 27.7% of these switched to oral risperidone. The Cox model showed that younger age (p = .001), longer duration of illness (p = .001), inpatient status at initiation (p = .002), and an RLAI dose of 25 mg/2 weeks (p.001) predicted greater probability of discontinuation.A small proportion of patients initiated on treatment with RLAI continued for 3 years. Outcome is likely to be improved by targeting RLAI treatment at specific patient groups and by using a dose of more than 25 mg/2 weeks.

Aims and MethodTo evaluate the prescribing of valproate in clozapine-treated individuals who may be at risk of seizure. We collected point-prevalent clinical characteristics and demographics of all in-patients prescribed clozapine in an acute mental health trust. Data were collected from case notes, electronic records and drug charts, and analysed against a set audit standard.ResultsData were collected for 81 in-patients. Of all deemed to be at risk of seizure (n=37) only 24% were prescribed valproate at a therapeutic plasma level.Clinical ImplicationsThe majority of patients prescribed clozapine at risk of seizures were not adequately protected from this risk. Clear guidelines are required.

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.A search using Embase, Medline, and Pubmed was conducted; and the literature was systematically reviewed. Studies meeting inclusion criteria were examined. The relationships between olanzapine dose, response, dopamine occupancy, and concentration were analyzed using statistical regression.Ten studies were included in the analysis for dose-response. The effect size-dose relationship showed a typical dose-response curve with minimal rise in slope for doses higher than 10 mg/d. For the dose-occupancy relationship, 6 studies were included. Doses more than approximately 12 mg/d were sufficient to block 65% of striatal D2 receptors. Doses higher than 20 mg led to minimally higher receptor occupancies. Fifteen studies were included in the meta-regression of olanzapine mean concentrations. A linear relationship between mean plasma concentration and mean dose was observed.Our review suggests that the likelihood of a favorable response with olanzapine is maximized at doses of 10 to 15 mg/d (perhaps lower in nonsmoking females). Higher doses may be considered if 15 mg is ineffective and if plasma level is less than 20 ng/mL on that dose. There is a direct linear relationship between olanzapine dose and plasma concentration. Therapeutic drug monitoring may be useful in patients who are suspected of nonadherence, where there is potential for a drug interaction, and in patients taking 15 mg/d or more and who have not reached clinical response.

Ethnicity may affect the prescribing of antipsychotic treatment. Previous UK studies conducted in south London have found few differences in antipsychotic prescribing quality for Black and White patients. This larger multicentre study examined the effect of ethnicity on antipsychotic prescribing quality in areas serving the largest proportions of Black patients in the UK. A cross-sectional survey with collection of multiple confounding factors potentially affecting outcomes in eight secondary care units in England over a three month period. Participants were Black or White inpatients prescribed regular antipsychotics on the day of the survey. Antipsychotic dose (expressed as a percentage of licensed maximum), high dose (being prescribed antipsychotic medication above maximum dose), polypharmacy (more than one antipsychotic prescribed), type (typical or atypical antipsychotic) and costs were the main outcome measures. Data were collected for 938 patients. There were no significant differences in any outcome by ethnicity: dose (adjusted percentage difference 0.97 [95% confidence interval (CI) −4.28, 6.22], p = 0.72); high dose (adjusted odds ratio (AOR) 0.98 [CI 0.63, 1.51], p = 0.92); polypharmacy prescribed (AOR 1.15 [CI 0.87, 1.51], p = 0.33); polypharmacy administered (AOR 1.08 [CI 0.78, 1.49], p = 0.66); use of typical antipsychotics (AOR 1.25 [CI 0.87, 1.79], p = 0.22); and cost (adjusted effect size 1.75 [CI −9.81, 13.31], p = 0.77). Antipsychotic prescribing practice did not differ between Black and White patients.

To evaluate the relationships between dose, plasma concentration, pharmacological activity and clinical outcome to evaluate the appropriateness of therapeutic drug monitoring (TDM) in patients receiving amisulpride.Literature search of Embase, Medline and PubMed databases.Amisulpride plasma concentration is closely correlated with dose (r(2) = 0.96, P0.0001), dopamine occupancy, response and with extra-pyramidal symptoms (EPS). Dose is correlated with response, dopamine occupancy and EPS. Optimal clinical response was found at doses of 400-800 mg/day, corresponding to plasma levels of approximately 200-500 ng/ml. EPS appears to be more reliably predicted by a plasma level above 320 ng/ml than by a particular dose.The effects and safety of amisulpride in the treatment of schizophrenia and schizoaffective disorder are predicted by daily dose. The plasma concentration threshold for response appears to be approximately 200 ng/ml. EPS are more reliably predicted by plasma level than by dose. TDM for patients prescribed amisulpride is thus of some clinical value.

Objective To evaluate relationships between aripiprazole dose, plasma level, pharmacologic activity, and clinical outcome in order to evaluate the potential for therapeutic drug monitoring. Data sources In August 2008, we searched Embase, MEDLINE, and PubMed databases using the keywords aripiprazole, plasma levels, plasma concentration, and therapeutic drug monitoring. Study selection Twenty-one reports were retrieved. Eight studies investigating the relationship between blood concentrations of aripiprazole and dose, dopamine D(2)/D(3) occupancy, and/or outcome and adverse effects were then selected. Data extraction All data concerning plasma or serum concentrations of aripiprazole were included if concentrations were reported in relation to a dose, dopamine occupancy, or clinical outcome. Those reports solely investigating drug interactions were not included. Data synthesis A strong correlation exists between aripiprazole dose and plasma concentration. Positron emission tomography analyses suggest that there are significant relationships between dopamine receptor occupancy and both aripiprazole dose and blood concentration. Dopamine receptor occupancy appears to reach a plateau at doses above 10 mg, supporting the observation found in dose-response studies that 10 mg/d is the optimal dose for aripiprazole. Conclusions The dose range for aripiprazole is well defined, and it reliably predicts plasma level, dopamine receptor occupancy, and clinical response. Plasma level variation appears to have minimal impact on clinical response, but it may predict some adverse effects. A putative target plasma level range of between 150 and 210 ng/mL is suggested. Therapeutic drug monitoring has limited value in the clinical use of aripiprazole, but it may be useful in assuring adherence and optimizing response in individuals.

The poster will discuss the work undertaken for the Higher Education Academy Development Fund project: 'Efficacy and appropriate use of electronic assessment techniques for computing subjects'.\ud The project is investigating whether innovative electronic assessment methods used for computing students at Sheffield Hallam University, such as phase tests which utilise electronic marking and feedback, enhance students' learning and offer suitable feedback. The project also explores the impact of these assessment methods on staff, especially in terms of time and workload, and their perception of the success of the methods. The project aims to develop an evidence base to inform discussions on how to use these assessment and feedback methods most effectively, and to produce good practice guidance for staff. \ud The poster will summarise the major findings of the research, evaluating the success of the electronic assessment methods and outlining good practice guidelines for any subject group considering utilising phase testing. Members of the project team will be available to discuss the project with attendees and answer any questions that they may have about the practical implications of the research outcomes.

Following the 2008 National Student Survey results, an investigation into the underlying reasons for low satisfaction with assessment and feedback amongst computing students was held to examine whether innovative electronic assessment and feedback methods such as phase tests utilising electronic marking and feedback, enhance student learning and to investigate the impact of these methods on staff. The staff who participated in the research found the perceptions of students to be surprising and valuable confirmation of the value of the testing method and the willingness of students to engage with it, a view which they were initially sceptical of. The experiences of staff who currently create and run phase tests and the perceptions of students from the questionnaires have enabled the project team to draw up practical guidance for staff members who may consider this form of testing.

Stairway preference and acceptability were investigated with psychophysical techniques. A series of six experiments was conducted where subjects ascended and descended 19 sets of stairways with different riser and tread (run) dimensions. Subjects were instructed to identify stairways that they considered acceptable, and the one stairway they most preferred. The optimum riser was 7.2 in (183 mm), and the optimum tread (run) was 11 or 12 in (279 or 300 mm). These dimensions were acceptable to both males and females, young and old, and subjects of greater or lesser stature. Larger dimensions were not as acceptable to shorter subjects, and smaller dimensions were not as acceptable to taller subjects. The 4-in (102 mm) riser was almost totally unacceptable, and never preferred. The 5.14 and 9-in (131 and 229 mm) risers were acceptable to less than one-third of the subjects, and rarely or never preferred. These results are compared with existing practices and recommendations.

Quetiapine is a widely used second-generation antipsychotic that is effective in the treatment of schizophrenia and bipolar mania. In recent years, various publications have suggested the possibility that, in some patients, higher than licensed dosages are necessary for full therapeutic effect. A 'high-dose' theory of quetiapine activity has developed, leading many prescribers to disregard the formal upper limit of the quetiapine dosage range (750 or 800 mg/day, depending on local labelling). In this review, we examine the clinical and neuroimaging data relating to the use of quetiapine in acute exacerbations of schizophrenia. Fixed-dose efficacy studies of immediate-release (IR) quetiapine suggest dosages of quetiapine of 150-450 mg/day are more effective than placebo and no less effective than dosages of 600 or 750 mg/day. A fixed-dose study of extended-release quetiapine indicated that dosages of 600 and 800 mg/day were equally efficacious and numerically superior to 400 mg/day. Dosages of IR quetiapine averaging between 254 and 525 mg/day have been shown to be equivalent in efficacy to standard dosages of conventional and other atypical antipsychotics. Pooled data support these findings. Effectiveness studies using quetiapine in daily doses averaging between 565 and 653 mg revealed quetiapine to be somewhat less effective than some comparator drugs. Support for the use of high-dosage quetiapine (>800 mg/day) is very limited: case reports, albeit numerous, describe quetiapine as showing therapeutic effects only at dosages above the licensed range; some data suggest widespread use of higher dosages in practice; and neuroimaging data suggest inadequate dopamine receptor occupancy at standard dosages (although these findings may reflect the low affinity of quetiapine for dopamine receptors). Overall, robust controlled data strongly suggest that the standard dosage range for quetiapine is appropriate for clinical use. The balance of evidence does not support the belief that higher dosages are required for full therapeutic effect, although higher dosage trials are ultimately required to confirm or refute this hypothesis.

Objective: To evaluate the effectiveness of aripiprazole in clinical practice. Method: Prospective follow-up of patients consecutively prescribed aripiprazole in an acute mental health unit. Retrospective analysis of outcome from casenotes. Results: Data were available on 228 patients. Fifty-one per cent discontinued aripiprazole over 6-month follow-up. Continuation with treatment was more likely in out-patients [relative risk (RR) 1.50; 95% CI: 1.13–2.00], those never before considered for clozapine treatment (RR 1.61, 95% CI: 1.06–2.44) and older patients [RR 1.05, 95% CI: 1.01–1.09 (per 5-year increase)]. The main reason for early discontinuation was the occurrence of minor adverse effects. Conclusion: Aripiprazole is effective in practice. Outcome is likely to be improved by careful patient selection and by attending to adverse effects experienced early in treatment.

Background: Clozapine is uniquely effective in refractory schizophrenia, but treatment attrition is high. There has been minimal formal study of the outcomes of stopping clozapine, beyond published observations of the time period immediately after cessation. Our aim was to establish medium-term outcome in patients stopping clozapine in normal clinical practice. Method: This study was a retrospective analysis of all subjects registered with Clozaril Patient Monitoring Service and treated in South London and Maudsley National Health Service (NHS) Trust who stopped clozapine between March 2002 and March 2005 after at least 1 year's treatment. Case note review was performed to determine relevant information for 1 year before and 1 year after discontinuation of clozapine, including subject details, reasons for stopping, and clinical outcome 1 year after discontinuation. The primary outcome measure was the Global Assessment of Functioning scale. Results: Thirty-five patients met inclusion criteria. Twelve had died while receiving clozapine. Of those followed up for 1 year after cessation (N = 23), mean Global Assessment of Functioning scores fell by 15 points (95% CI = 6.6 to 24.3; p =.002). Days spent in hospital rose from a mean of 74.1 (SD = 137.3) to 119.8 (SD = 143.5) (p =.214). Conclusion: Discontinuation of clozapine has a marked negative impact on clinical status. Death is a common cause of clozapine cessation.

Objective To systematically review published and unpublished efficacy studies of agomelatine in people with depression.Design Systematic review and meta-analysis.Data sources Literature search (Pubmed, Embase, Medline), Cochrane Central Register of Controlled Trials, European Medicines Agency (EMA) regulatory file for agomelatine, manufacturers of agomelatine (Servier).Eligibility criteria Double blind randomised placebo and comparator controlled trials of agomelatine in depression with standard depression rating scales.Data synthesis Studies were pooled by using a random effects model with DerSimonian and Laird weights for comparisons with placebo and comparator antidepressant. The primary efficacy measure (change in rating scale score) was summarised with standardised mean difference (SMD; a measure of effect size) and secondary outcome measures with relative risks. All results were presented with 95% confidence intervals. Statistical heterogeneity was explored by visual inspection of funnel plots and by the I-2 statistic. Moderators of effect were explored by meta-regression.Results We identified 20 trials with 7460 participants meeting inclusion criteria (11 in the published literature, four from the European Medicines Agency file, and five from the manufacturer). Almost all studies used the 17 item Hamilton depression rating scale (score 0-50). Agomelatine was significantly more effective than placebo with an effect size (SMD) of 0.24 (95% confidence interval 0.12 to 0.35) and relative risk of response 1.25 (1.11 to 1.4). Compared with other antidepressants, agomelatine showed equal efficacy (SMD 0.00, -0.09 to 0.10). Significant heterogeneity was uncovered in most analyses, though risk of bias was low. Published studies were more likely than unpublished studies to have results that suggested advantages for agomelatine.Conclusions Agomelatine is an effective antidepressant with similar efficacy to standard antidepressants. Published trials generally had more favourable results than unpublished studies.