Clozapine remains the drug of choice for treatment-resistant schizophrenia. As a consequence of its long history and complex pharmacology, we suspected wide variation in the regulations of clozapine use across different countries. The summaries of product characteristics (SPCs) from clozapine manufacturers, as well as local and national guidelines in the following selected countries, were reviewed: China, Denmark, Ireland, Japan, The Netherlands, New Zealand, Romania, the UK and the US. Clozapine is available as tablets in all countries, as an oral suspension in all included countries, with the exception of Japan and Romania, as orally disintegrating tablets in the US and China, and as an injectable in The Netherlands. General practitioner prescribing is only available in The Netherlands, New Zealand, the UK and the US, although with some restrictions in some of the countries. In Ireland and China, clozapine is only dispensed through hospital pharmacies. Hematological monitoring is mandatory in all countries but varies substantially in frequency, e.g. in Denmark hematologic monitoring is mandatory weekly for 18 weeks, followed by monthly monitoring, compared with Japan where blood work is required weekly for 26 weeks, followed by biweekly hematologic monitoring thereafter. In most included countries, with the exception of Denmark, Romania and The Netherlands, the manufacturer provides a mandatory hematological monitoring database, and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results. Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine. Regulations of clozapine vary widely with regard to rules of prescribing and monitoring. A worldwide update and harmonization of these regulations is recommended.

No abstract

Routine screening for these modifiable risk factors followed by active intervention where appropriate could significantly reduce morbidity and mortality in this patient group.

Testing for diabetes was undertaken in less than half of the patients studied. Testing was more common in those receiving atypical antipsychotics. Apparent differences in claimed causal association of the use of some antipsychotics with diabetes may in part reflect different rates of testing.

Risperidone long-acting injection (RLAI) is the first depot preparation of the so-called atypical antipsychotics. Efficacy is well established but effectiveness and factors predicting favourable outcome have only tentatively been evaluated. Our aim was to evaluate naturalistic outcome in patients given RLAI in normal clinical practice and to uncover factors predicting favourable outcome. Prescribers provided details of all patients prescribed RLAI on starting treatment and fortnightly thereafter. Patients were followed up for 6 months or until RLAI was discontinued. Main outcome measures were continuation with RLAI at 6 months and improvement in Clinical Global Impression (CGI) score. These outcomes were compared with clinical and patient data. Of 250 patients starting RLAI, 118 (47.2%) were still receiving it at 6 months. Patients were more likely to continue treatment with RLAI to 6 months if older than 55 yr [odds ratio (OR) 3.13, 95% CI 1.32-7.40, p=0.006] and if receiving a dose of >25 mg/2 wk RLAI (OR 2.37, 95% CI 1.40-3.99, p<0.001). An improvement of one point on the CGI scale (first vs. last assessment) was more likely in those prescribed RLAI because of poor prior adherence (OR 2.28, 95% CI 1.35-3.86, p=0.002) and less likely in those who had previously been prescribed clozapine (OR 0.29, 95% CI 0.14-0.61, p=0.001). Overall outcome of RLAI treatment is moderately good but better still when prescribed because of prior poor adherence and for more elderly patients. RLAI is less suitable for those who have previously received clozapine.

No abstract

The associations between psychosis, antipsychotic drugs and diabetes mellitus have not been precisely defined but it has been repeatedly suggested that atypical antipsychotics are more likely to give rise to diabetes than are conventional drugs. This belief is largely based on healthcare database analyses which, in part, rely on the assumption that all cases of diabetes are identified in practice. We examined records of 606 hospitalized patients receiving antipsychotic treatment and found an apparent prevalence of diabetes and impaired fasting glucose of 6.4%. From this sample of patients, we investigated 166 patients (fasting blood samples) who were not known to have any disorder of glucose homeostasis and identified 10 cases of impaired fasting glucose and nine cases of diabetes mellitus (11.4% of those tested). Nine of these cases had documented evidence of previous testing for diabetes. Apparent prevalence of diabetes and impaired fasting glucose was 16.9% in those tested in practice or the study. Diagnosis was significantly associated with age [odds ratio (OR) 1.02] and treatment duration with current drug (OR 1.01). Adjusted ORs of diagnosis were not significantly different for any atypical antipsychotic compared with conventional drugs. It is concluded that there was a clinically significant prevalence of undiagnosed diabetes and impaired fasting glucose in those individuals receiving antipsychotics. Importantly, database analyses may underestimate the true prevalence of diabetes in similar populations and erroneously ascribe increased risk to certain drug treatments.

Switching to RLAI was associated with a continuation of the trend for increased bed stay and use of healthcare resources.