Abstract
BackgroundThe patients included in RCTs represent a small atypical minority of the entire patient population, as up to 80–90% of patients are excluded because of mental or physical comorbidity, suicidal or antisocial behaviour, or substance abuse. Concerning clozapine, this means that those most severely ill patients having the greatest potential benefit from clozapine treatment are excluded from RCTs. Another major limitation of RCTs is that when very important but relatively infrequent phenomena, such as suicide or death is studied, exclusion of high risk patients and insufficient statistical power prevent obtaining statistically significant findings.MethodsObservational studies can overcome these obstacles by using nation-wide electronic databases of hospitalization, mortality, and filled prescriptions. However, the main problem with these observational studies is selection bias. Although the most important covariates could be adjusted in the statistical analysis, there always remains residual confounding associated with the personal characteristics of each patient. One way to overcome this problem is to use within-individual analysis, in which each individual is his or her own control. In this approach, the exposure periods of each individual are compared with the non-exposure periods of the same individual.ResultsThis far, 3 large observational studies using traditional between-subject analyses have found that when compared with other oral antipsychotics, clozapine is associated with the best outcome concerning risk of re-hospitalization, and 4 large cohort studies have shown that clozapine is associated with the lowest mortality. The only cohort study this far using within-individual analyses showed that in a nation-wide cohort of 29,823 patients, clozapine was associated with the lowest risk of treatment failure (defined as psychiatric re-hospitalization, suicide attempt, discontinuation or switch to other medication, or death).DiscussionA large body of observational studies shows that clozapine has better real-world effectiveness than any other oral antipsychotic treatment.
Highlights
The patients included in RCTs represent a small atypical minority of the entire patient population, as up to 80–90% of patients are excluded because of mental or physical comorbidity, suicidal or antisocial behaviour, or substance abuse
The exposure periods of each individual are compared with the non-exposure periods of the same individual. This far, 3 large observational studies using traditional betweensubject analyses have found that when compared with other oral antipsychotics, clozapine is associated with the best outcome concerning risk of re-hospitalization, and 4 large cohort studies have shown that clozapine is associated with the lowest mortality
We assessed the effect of clozapine treatment on the rate of violent and non-violent offending in the whole of Sweden, taking account of time-changing sociodemographic characteristics and the combination of violent and non-violent offences within individual convictions
Summary
For patients with refractory schizophrenia, clozapine is the drug of first choice. many refractory patients never receive this drug. Methods: In this cluster-randomized trial, 23 Dutch ambulatory care teams were randomized into 2 conditions: (A) coordination of clozapine monitoring by a Nurse Practitioner, versus (B) Treatment As Usual: coordination of clozapine monitoring by the responsible physician (usually a psychiatrist). We followed the teams for 15 months, during which period we counted the numbers of patients who started with clozapine. We assessed the safety of the clozapine monitoring by measuring the number of weekly lab exams performed during the first 18 weeks of treatment and counting serious adverse events (SAE). Clozapine-monitoring by an NP appears to be just as safe as monitoring by a physician These results strongly support the idea that the presence of dedicated staff to arrange and monitor the initiation of clozapine enables the use of this drug
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