No abstract

Treatment of cognitive impairments is feasible in both early-course and chronic schizophrenia, but the clinical meaningfulness and generalization to functioning appear to be more substantial when delivered early. Cognitive remediation should be considered a tool for early intervention in schizophrenia.

Clozapine is an atypical antipsychotic medication with proven efficacy in the management of refractory schizophrenia. It is also recommended for patients who do not tolerate the extrapyramidal adverse effects of traditional antipsychotic medications. However, the therapeutic promise of clozapine has been limited by a higher incidence of agranulocytosis. Currently, plasma clozapine concentrations are not routinely used in clinical management. Therapeutic effects are monitored empirically during a 6 to 8 week titration period in which the dosage is raised to 300 to 450 mg/day. Clozapine nevertheless fulfils a number of criteria which make it a candidate for therapeutic monitoring. These include an identifiable therapeutic range, an unpredictable dose-concentration relationship between patients, a potential for clinically relevant pharmacokinetic interaction with other drugs and a high probability of patient noncompliance. The therapeutic threshold plasma concentration appears to be about 400 micrograms/L. Concentrations above 1000 micrograms/L increase the risk of adverse effects on the central nervous system (confusion, delirium and generalised seizures). There is no evidence to link increased concentrations of clozapine or its metabolite to the development of agranulocytosis. We conclude that therapeutic drug monitoring can play a useful role in the clinical management of patients treated with clozapine. The clinician is advised to primarily use clinical judgement during dosage escalation, but intermittent monitoring is recommended to quickly optimise a therapeutic dosage for each patient. At steady state, occasional measurements could be made when clinical signs indicate possible toxicity or lack of effect (possibly caused by a lack of compliance or drug interaction). Long term monitoring would, in our view, not be necessary.

Clinically stabilised patients with schizophrenia can provide accurate health state descriptions and assign them utilities with a fair degree of reliability and validity. Utility evaluations based on patients' self-appraisals can be seen as potential tools in outcome studies and clinical trials involving patients with schizophrenia, but the methodology requires further refinement to accommodate the limitations imposed by the patients' disturbed mental status.

The patterns of use of psychiatric emergency services in Saskatoon, Saskatchewan were studied. A total of 576 patients who had received psychiatric emergency care from any of the four major health care facilities in Saskatoon during a three month period were included in the study. Visits for psychiatric emergency services during the study period represented 2.32% of the total number of visits to emergency facilities. Most patients with psychiatric emergencies went to hospitals with psychiatric units. The characteristics of patients served by the four facilities and those who visited the psychiatric emergency services on more than one occasion during the study period are reported. The implications of these findings for health care planning are discussed.

These results suggest that both generating systems metabolized clozapine to toxic products. Some products may play a role in clozapine-induced agranulocytosis. Of diagnostic relevance is the observation the HRP-H2O2 produces significantly greater toxicity in cells from patients with agranulocytosis than in cells from control patients. Although the exact mechanism(s) of drug activation in vivo remains unclear, the bioactivation of clozapine by HRP-H2O2 may be a useful in vitro tool for predicting which patients are at risk for agranulocytosis before initiation of therapy.

The purpose was to generate a theory of the psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications. A grounded theory research design was used to guide the study. Semi-structured interviews were the method of data collection, and analysis was performed using constant comparison. Using theoretical sampling, a sample of 11 participants with first-episode psychosis prescribed atypical antipsychotics for at least 8 weeks, and five participants with a diagnosis of chronic schizophrenia prescribed atypical antipsychotic medication for at least 3 years were recruited from an outpatient psychiatric programme. Contextual factors influencing weight management were: accessibility to resources, unstructured lifestyle, and others' perception of weight. Conditions influencing weight management were: rapid weight gain, insatiable hunger and lack of motivation boosters. Participants' early responses to weight gain included discontinuing medications, choosing lower-calorie foods, using walking in daily activities as exercise, accepting weight gain and trying to manage weight but giving up. The consequences revealed from data analysis were contemplating weight management and not trying, as the barriers to weight management exceeded the facilitators. The theoretical framework developed in this study can assist with the understanding and management of weight gain among this unique population.

Ob jec tive: To de ter mine the re la tion be tween se rum clo zap ine and nor-clozapine lev els and blood cell counts dur ing clo zap ine treat ment. Method:We un der took a pro spec tive lon gi tu di nal study of 37 con secu tive pa tients with a di ag no sis of schizo phre nia treated with clo zap ine. We ob tained in formed con sent and then de ter mined se rum con cen tra tions of clo zap ine and nor-clozapine weekly. Clo zap ine was ad min is tered daily in di vided doses given every 12 hours and ad justed ac cord ing to clini cal guide lines for its use. Sam ples for se rum con cen tra tions were taken at steady state, im medi ately be fore the next morn ing's dose, for 4 to 8 weeks. Com plete blood counts (CBC), weight, and vi tal signs (that is, blood pres sure, pulse, and tem pera ture) were also moni tored weekly be fore the morn ing's dose of clo zap ine was ad min is tered.Re sults: Analy ses of vari ance showed no sig nifi cant changes over the 8-week treat ment course in the ob served mean white blood count (WBC), red blood count (RBC), neu trophils, and lym pho cytes counts, or in the he mo glo bin and he ma to crit. Only a few weak corre la tions (r < 0.21) were found be tween these he ma to logi cal pa rame ters and the meas ures of se rum clo zap ine and nor-clozapine. Con clu sions:The mecha nism of clozapine-induced he ma to tox ic ity at the thera peu tic dosage range is proba bly not by di rect tox ic ity of clo zap ine or nor-clozapine to the blood cells or their pre cur sors. The for ma tion of the cy to toxic nitrenium com pound from clo zap ine by neu tro phils may be nec es sary. Clini cal Im pli ca tions• The white blood count (WBC), red blood count (RBC), neu tro phils, and lym pho cytes counts show no sig nifi cant changes within 8 weeks of clo zap ine treat ment at thera peu tic dosages.• There is no re mark able cor re la tion be tween blood counts and se rum clo zap ine and norclozapine lev els.• The clo zap ine dos age is sig nifi cantly and highly cor re lated with lev els of se rum clo zap i ne and nor-clozapine, but not with the se rum nor-clozapine-clozapine ra tio. Limi ta tions• The sam ple size was mod er ate.• Only data from the first 8 weeks of treat ment were in cluded.• Cross-cultural rep li ca bil ity is un known.