An inquiry into various aspects of clozapine use:prescription, monitoring and mortality

This thesis concerns clozapine, an antipsychotic for patients with schizophrenia for whom other antipsychotics were not effective. The treatment is labor-intensive because of the weekly blood tests during the first 18 weeks. Is case of an abnormality (1-2%), the treatment has to be discontinued. That is why the drug is prescribed less often than desired. This research examined prescription rates in outpatient teams and an intervention to stimulate prescribing: delegating the clozapine monitoring to nurse practitioners. It was found that the prescription rates in the Netherlands differed strongly per team and are on average high compared to those in other countries. The intervention did not lead to significantly more prescriptions. The research also used data on the Danish population to investigate whether the use of clozapine is associated with an increased mortality. One would expect an increased cardiovascular mortality because this drug often leads to serious obesity, but this was not found. No difference was found between clozapine and other antipsychotics in all-cause mortality, cardiovascular mortality or suicides. The research did find a high risk of suicide after discontinuation of clozapine

Use of cardiovascular and antidiabetic drugs before and after starting with clozapine versus other antipsychotic drugs:a Dutch database study

Reports of decreased mortality among patients with schizophrenia who use clozapine may be biased if clozapine is prescribed to relatively healthy patients and if intensive monitoring during its use prevents (under-treatment of) somatic disorder. We aimed to assess whether there is a difference in: (1) somatic comorbidity between patients who start with clozapine and those who start with other antipsychotics and (2) prescribed somatic medication, between patients using clozapine and those using olanzapine. Cohort study based on insurance claims (2010-2015). After selecting new users of antipsychotics and those who subsequently switched to clozapine (N = 158), aripiprazole (N = 295), olanzapine (N = 204) or first-generation antipsychotics (N = 295), we compared the clozapine starters to others on cardiovascular or diabetic comorbidity. Those using clozapine and olanzapine were compared on new prescriptions for cardiovascular or antidiabetic drugs. The OR(adj)of cardiovascular or diabetic comorbidity among other starters compared with clozapine starters was 0.77 [95% confidence interval (CI): 0.43-1.39], that is, a nonsignificantly increased prevalence associated with clozapine was found. Users of clozapine received significantly more new prescriptions for cardiovascular or antidiabetic medication (ORadj: 2.70, 95% CI: 1.43-5.08). Starters with clozapine were not cardiovascular/metabolic healthier than starters with other antipsychotics. During its use, they received more somatic treatment

Prescription and Underprescription of Clozapine in Dutch Ambulatory Care

Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients). Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH). Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8-34.7% (mean: 23.0%), type 2: 0-8.2% (mean: 3.5%), type 3: 1.7-15.6% (mean: 6.9%), type 4: 1.8-16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0-90.9% (mean: 68.8%). These figures were lower in early intervention teams. Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher

Belastende gebeurtenissen die patiënten meemaken gedurende hun verblijf op een gesloten opnameafdeling van een psychiatrisch ziekenhuis.

Yvonne van der Zalm heeft een presentatie gegeven over haar afstudeeronderzoek op de wetenschapsmiddag van Rivierduinen. Een opname op een gesloten opnameafdeling van een psychiatrisch ziekenhuis kan erg belastend zijn voor patiënten. Naast de belasting die door dwangmaatregelen wordt veroorzaakt, zijn er ook veel andere belastende gebeurtenissen tijdens een opname. Er is nog weinig onderzoek gedaan naar welke gebeurtenissen belastend zijn voor patiënten en hoeveel last ze veroorzaken

Experiences of Patients in Acute and Closed Psychiatric Wards: A Systematic Review

PURPOSE: To obtain insight into the patients' experiences during treatment in an acute, closed psychiatric ward. DESIGN AND METHODS: A systematic literature search was conducted in the databases Medline, Embase, CINAHL, and Cochrane. FINDINGS: Ten articles were selected. Four main themes emerged from the literature: (a) the inappropriate use of the ward rules, (b) nurses' lack of time for interacting with patients, (c) the feeling of humiliation, and (d) the involvement of significant others. PRACTICE IMPLICATIONS: Nurses can use the findings of this systematic review to improve quality of care in acute psychiatric units

Psychiatric Nursing Care for Adult Survivors of Child

PURPOSE: To determine what is known from the literature about nursing care of psychiatric patients with a history of child maltreatment. CONCLUSIONS: Psychiatric nurses underline the importance of a routine inquiry of child abuse on admission of patients to psychiatric care, but are reluctant to ask about child abuse. They often feel insufficiently competent to respond effectively to patients with a history of child maltreatment. PRACTICE IMPLICATIONS: Psychiatric nurses need training in how to assess a history of child abuse and the late-life consequences of abuse in adult psychiatric patients. They also need to be trained to respond effectively to these patients

Prescription and Underprescription of Clozapine in Dutch Ambulatory Care

Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients).Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH).Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8–34.7% (mean: 23.0%), type 2: 0–8.2% (mean: 3.5%), type 3: 1.7–15.6% (mean: 6.9%), type 4: 1.8–16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0–90.9% (mean: 68.8%). These figures were lower in early intervention teams.Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher.Registration number: NTR5135 http://www.trialregister.nl/trialreg/index.as

Clozapine and mortality:A comparison with other antipsychotics in a nationwide Danish cohort study

Objective To compare the mortality in people using clozapine to that of people using other antipsychotics. Methods Danish incidence cohort of 22,110 patients with a first diagnosis of non-affective psychotic disorder (1995-2013) and a prevalence cohort of 50,881 patients ever diagnosed with such a disorder (1969-2013). Hazard ratios (HR) were calculated for the antipsychotic drug used at the time of death ("current use": incidence and prevalence cohort) and for the drug used for the longest at that moment ("cumulative use": incidence cohort), using a Cox model with adjustment for somatic comorbidity. Clozapine was the reference drug. Results As for current drug use, the risk of suicide was higher among users of other antipsychotics in the incidence (HRadj = 1.76; 95% CI 0.72-4.32) and prevalence (HRadj = 2.20; 95% CI 1.35-3.59) cohorts. There was no significant difference in all-cause or cardiovascular mortality in the two cohorts. Cumulative use of clozapine was not associated with an increased cardiovascular mortality. Cumulative use of other antipsychotics for up to 1 year was associated with a lower all-cause mortality and suicide risk than a similar period of clozapine use (all-cause: HRadj = 0.73; 95% CI 0.63-0.85, suicide; HRadj = 0.65; 95% CI 0.46-0.91). Conclusion The results indicate that the use of clozapine is not associated with increased cardiovascular mortality. We found opposing trends toward a lower risk of suicide during current use of clozapine and a higher risk of suicide associated with cumulative use up to 1 year. This suggests that clozapine cessation marks a period of high risk of suicide

Data_Sheet_1_Prescription and Underprescription of Clozapine in Dutch Ambulatory Care.docx

<p>Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients).</p><p>Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH).</p><p>Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8–34.7% (mean: 23.0%), type 2: 0–8.2% (mean: 3.5%), type 3: 1.7–15.6% (mean: 6.9%), type 4: 1.8–16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0–90.9% (mean: 68.8%). These figures were lower in early intervention teams.</p><p>Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher.</p><p>Registration number: NTR5135 http://www.trialregister.nl/trialreg/index.asp</p