Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records

Ingimarsson, Oddur; MacCabe, James H.; Jónsdóttir, Halldóra; Sigurðsson, Engilbert

doi:10.3109/08039488.2016.1155234

Cited by 20 publications

(16 citation statements)

References 25 publications

(27 reference statements)

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“…This continuous risk of ileus is different than with agranulocytosis where around 80% of the overall risk is present during the first half year of treatment but only 20% remain as the cumulative risk in due course during long-term treatment (17,18). The prevalence of ileus in this study is higher than the prevalence of agranulocytosis in Iceland and in other larger studies where the prevalence has been reported to be 0.7% (17)(18)(19). The case fatality in ileus has been reported be in the range from 7.3% -27.5% (9-11) versus 3% in agranulocytosis (20, 21) so physicians should be at least as vigilant with regard to constipation and the development of ileus as they are with neutropenia and the possible development of agranulocytosis.…”

Section: Resultscontrasting

confidence: 70%

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland

Ingimarsson¹,

MacCabe

Sigurðsson

2018

Nordic Journal of Psychiatry

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Section: Resultscontrasting

confidence: 70%

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland

Ingimarsson¹,

MacCabe

Sigurðsson

2018

Nordic Journal of Psychiatry

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“…4,5 TRS is commonly defined as 'failure to respond to two or more antipsychotics (one of which should be a second-generation antipsychotic) given in an adequate dose for at least 6-8 weeks'. 6,7 Around 30% of patients with schizophrenia are treatment resistant. 8,9 Of those, approximately 60% do not respond to clozapine.…”

Section: Current Treatment Options After Clozapine Cessationmentioning

confidence: 99%

In the aftermath of clozapine discontinuation: comparative effectiveness and safety of antipsychotics in patients with schizophrenia who discontinue clozapine

et al. 2020

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Background Although clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided. Aims To compare the real-world effectiveness of antipsychotics after clozapine cessation. Method From Finnish registry data (1995–2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences. Results Compared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40–0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48–0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53–0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27–0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43–0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61–0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09–0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17–0.40; P < 0.0001). Conclusions Clozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.

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“…Even though clozapine has a high burden of various adverse side effects we have reported that over 70% of patients that commence clozapine treatment in Iceland remain on it long term [5]. A pharmacogenetic test for agranulocytosis with adequate predictive validity is unlikely and would likely present ethical challenges [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland

Ingimarsson¹,

MacCabe²,

Jónsdóttir³

et al. 2016

BMC Psychiatry

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BackgroundData on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia.MethodsThe present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well.ResultsThe median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500–1900 neutrophils/mm3). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500–1400 /mm3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine.ConclusionsNeutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

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Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records

Cited by 20 publications

References 25 publications

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland

In the aftermath of clozapine discontinuation: comparative effectiveness and safety of antipsychotics in patients with schizophrenia who discontinue clozapine

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland

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