Prescription and Underprescription of Clozapine in Dutch Ambulatory Care

Abstract

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.asp

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

“…Assuming the prevalence of treatment resistance is about 30%, the prescription rate in Denmark is about 15%. In The Netherlands prescription rates are relatively high (21.6%) (van der Zalm et al, 2018), which may explain the less restrictive use in patients with somatic comorbidity.…”

“…Surprisingly, a recent meta-analysis (Vermeulen et al, 2019) found a significantly decreased mortality during clozapine use [mortality rate ratio: 0.56; 95% confidence interval (CI): 0.36-0.85; P = 0.007). However, as we discussed earlier (van der Zalm et al, 2019), the results of this meta-analysis may be biased because the effect sizes had not been adjusted for age. Nevertheless, some studies (Tiihonen et al, 2009;Hayes et al, 2015) using age-adjusted effect measures reported a decreased mortality during the use of clozapine compared with the use of other antipsychotics.…”

Clozapin in der Behandlung schizophrener Psychosen Patientencharakteristika und antipsychotische Kombinationstherapien bei einem Behandlungsjahrgang eines psychiatrischen Versorgungskrankenhauses

“…Das atypische Antipsychotikum Clozapin hat einen besonderen Stellenwert in der Therapie von Psychosen aus dem schizophrenen Formenkreis. Leitlinien empfehlen Clozapin bei Therapieresistenz [1][2][3], außerdem wird es unter anderem bei assoziierten Symptomen, wie: extrapyramidale Bewegungsstörungen [4] , aggressives Verhalten [5] und Suizidalität [6] verordnet. Seit den Publikationen von Naber und Kollegen aus den 1990er-Jahren [7,8]…”

Moving forward with clozapine

“…Since the foundation of the DCCG, the number of Dutch outpatients on clozapine has increased from 7764 in 2004 to 14 628 in 2019, an increase of 88%, which compares favourably with the 36% increase in the number of patients on other antipsychotics during the same period (15). In the Netherlands in 2016, the mean prescription rate of clozapine in 20 flexible assertive community (FACT) teams treating 2286 schizophrenia-spectrum patients was 23.0% (16). Nevertheless, 6.9% of the schizophrenia-spectrum patients who were eligible for clozapine treatment were not receiving it (range 1.7-15.6 %).…”