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Objective: To assess whether clozapine is likely to be more cost-effective than other second-generation antipsychotics (SGAs) in people with schizophrenia., Methods: An integrated clinical and economic multicenter, rater-blind, randomized controlled trial (RCT) compared clozapine to the class of other SGAs, using the perspectives of the National Health Service, social support services, and patients. The practice setting was secondary and primary care in the United Kingdom; patients were followed for 1 year. Incremental cost-effectiveness ratios (ICERs), net benefit statistics, and cost acceptability curves were estimated., Results: The ICER for clozapine was 33,240 pound per quality-adjusted life-year (QALY) (range 23,000-70,000 pound for the sensitivity analyses). The proportion of simulations when clozapine was more cost-effective than other SGAs reached 50% if decision-makers are prepared to pay 30,000 pound to 35,000 pound per QALY. This is at the top of the range of acceptable willingness-to-pay values per QALY implied by decisions taken by the National Institute for Health and Clinical Excellence (NICE)., Conclusions: This study adds to a limited body of evidence comparing clozapine to other SGAs and is the first economic and clinical RCT to compare clozapine to the class of other SGAs using the lower cost of generic clozapine and a pragmatic trial design. Policy decisions by the NICE suggest that additional reasons would be needed to accept clozapine as effective and efficient if it had a high probability of having ICERs more than 35,000 pound per QALY. The results and limitations of the analysis suggest that there is still a need for further economic evaluation of clozapine.

Context: Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms., Objective: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs., Design: A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis., Setting: Fourteen community psychiatric services in the English National Health Service., Participants: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects., Interventions: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist., Main Outcome Measures: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care., Results: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar., Conclusions: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.

There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.

Objectives To examine clinicians' attitudes regarding the relative benefits and risks of conventional and atypical antipsychotic medication, and the perceived validity of the CUtLASS study. To examine the attitudes of participant clinicians' regarding the operation and administration, and the potential clinical impact of the findings. Method Two hundred and sixty-two clinicians were each sent an anonymous questionnaire, and invited to indicate whether they agreed or disagreed with each of to nine statements (from agree to disagree). Results Of the 112 clinicians who responded, 71% supported the CUtLASS study. Thirty-nine percent agreed with the statement that the clinical efficacy of atypicals was superior to conventional antipsychotics, while 27% disagreed and 34% were undecided. Thus, two-thirds of participating clinicians revealed no uncertainty on a key question being tested in the CUtLASS study. Further, the vast majority (97%) considered that atypicals were associated with less severe side effects. Conclusions In clinical studies, recruitment strategies relying on referrals from clinicians may find that some clinicians identify fewer patients than expected. This can lead to a relatively low yield of potential study subjects and possibly a selection bias. Surveys of clinicians approached to participate in clinical studies provide a potential mechanism to explore attitudes relevant to participant recruitment. [ABSTRACT FROM AUTHOR]

A response by Peter B. Jones, Peter Elton, Linda Davies, Graham Dunn, Helen Lloyd, Karen P. Hayhurst, Robin M. Murray, Alison Marwick, and Shôn Lewis to a letter to the editor about their article on the properties of sulpiride including design of Cost of Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS) 1 and other major trials in the previous issue is presented.