Reasons for clozapine discontinuation in patients with treatment-resistant schizophrenia

Üçok, Alp; Yağcıoğlu, Elif Anıl; Yıldız, Mustafa; Kaymak, Semra Ulusoy; Saka, Meram Can; Taşdelen, Rümeysa; Danacı, Ayşen Esen; Şenol, Şevin Hun

doi:10.1016/j.psychres.2019.01.110

Cited by 33 publications

(49 citation statements)

References 23 publications

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“…The duration of illness prior to clozapine initiation was often long (9–25 years in the meta-analysis), which may reflect clinical practice (Üçok et al, 2019), and limits inference about the clinical and demographic predictors of clozapine response when initiated in earlier stages of illness. There was large variation in the number of patients identified as clozapine non-responders, which may be due to variation in clozapine response definition and duration of follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…To capture the complexity of therapeutic response, we included articles that used clinical, service use and functional measures of clozapine response, whether reported as categorical or continuous outcome variables. All-cause discontinuation of clozapine was not an eligible outcome measure because factors other than lack of efficacy may contribute to cessation of clozapine treatment (Legge et al, 2016; Üçok et al, 2019). The meta-analysis included a subset of articles where clozapine response was defined as symptomatic improvement on clinical rating scales (see Section ‘Meta-analysis’).…”

Section: Methodsmentioning

confidence: 99%

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Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis

et al. 2021

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Clozapine is the only licensed pharmacotherapy for treatment-resistant schizophrenia. However, response to clozapine is variable. Understanding the demographic and clinical features associated with response to clozapine may be useful for patient stratification for clinical trials or for identifying patients for earlier initiation of clozapine. We systematically reviewed the literature to investigate clinical and demographic factors associated with variation in clozapine response in treatment-resistant patients with schizophrenia spectrum disorders. Subsequently, we performed a random-effects meta-analysis to evaluate differences in duration of illness, age at clozapine initiation, age of illness onset, body weight and years of education between clozapine responders and non-responders. Thirty-one articles were eligible for qualitative review and 17 of these were quantitatively reviewed. Shorter duration of illness, later illness onset, younger age at clozapine initiation, fewer hospitalisations and fewer antipsychotic trials prior to clozapine initiation showed a trend to be significantly associated with a better response to clozapine. Meta-analysis of seven studies, totalling 313 subjects, found that clozapine responders had a significantly shorter duration of illness compared to clozapine non-responders [g = 0.31; 95% confidence interval (CI) 0.06–0.56; p = 0.01]. The results imply that a delay in clozapine treatment may result in a poorer response and that a focus on prompt treatment with clozapine is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis

et al. 2021

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“…First, it is the only antipsychotic indicated for treatment-resistant schizophrenia, a form of illness which, by definition, requires that individuals suffer from persistent psychosis (14)(15)(16)(17)(18). In addition, clozapine is burdened by substantial side effects and this too can negatively influence adherence (19,20).…”

Section: Introductionmentioning

confidence: 99%

Adherence to clozapine vs. other antipsychotics in schizophrenia

Takeuchi

Borlido

Sanches

et al. 2020

Acta Psychiatr Scand

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Background: To date, there have been no studies evaluating adherence to clozapine with electronic adherence monitoring (EAM) such as the Medication Event Monitoring System (MEMS Ò). Methods: In outpatients with schizophrenia, we conducted a 3-month prospective study investigating antipsychotic adherence with EAM (eCAP Ò). Participants were treated with different oral antipsychotics, including clozapine, and blind to EAM monitoring; all were on antipsychotic monotherapy administered once daily. Outcome measures included adherence rate, missed dose, and medication gap. Adherence trajectory patterns were also analyzed for clozapine vs. other antipsychotics collectively. Results: A total of 111 patients were included in the study; 33 and 78 patients received clozapine or other antipsychotics, respectively. Adherence rates, defined as proportion of days that the subject took the medication at the prescribed time AE 3 h and proportion of subjects with ≥80% adherence, were numerically higher in patients receiving clozapine vs. other antipsychotics (72.0% vs. 65.1%, P = 0.10; 49.5% vs. 35.7%, P = 0.11, respectively). Along similar lines, some of the missed dose and medication gap outcomes were significantly better in patients receiving clozapine vs. other antipsychotics. Three adherence trajectory patterns were identified for both clozapine and other antipsychotics, with two shared by both groups (i.e., low adherence with a slight decrease over time; high and stable adherence). Conclusion: Findings suggest that in patients with schizophrenia clozapine adherence is at least comparable, if not slightly better, compared with other antipsychotics.

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“…Despite its benefits, clozapine discontinuation is common (Cho et al, 2016;Gee et al, 2018). Ucok et al (2019) found that those who discontinued clozapine tended to have a longer history of illness, incomplete treatment response, more hospitalisations prior to clozapine initiation and be older. Gee et al (2018) found that male patients had two-fold higher odds of stopping clozapine and that discontinuation usually occurred due to patient refusal of treatment.…”

Section: Number Of Patients N=13mentioning

confidence: 99%

“…Cho et al (2016) reported that most discontinuations were due to side effects and patients' own decisions. Ucok et al (2019) found that side effects were the most common reason for cessation. While there are guidelines advising clozapine discontinuation by physicians in some instances, including severe agranulocytosis, of interest, the US Food and Drug Administration changed their clozapine usage guidelines in 2015 to allow greater flexibility to continue or rechallenge clozapine in patients with neutropenia on clozapine (Bastiampillai et al, 2016).…”

Section: Number Of Patients N=13mentioning

confidence: 99%

Clozapine use – has practice changed?

Rowntree¹,

Murray²,

Fanning³

et al. 2020

J Psychopharmacol

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Background: One-third of individuals with schizophrenia have treatment-resistant illness. Of these, up to 60% will respond to clozapine treatment. Aims: This study retrospectively examined clozapine prescribing patterns against National Institute for Health and Care Excellence (NICE) guidelines as treatment-resistant illness emerged in a first-episode psychosis cohort. Methods: A total of 339 individuals with a first-episode psychosis were included in the study. Clozapine prescribing patterns were compared against the NICE guidelines and the impact of clozapine use on one index of service utilisation (hospitalisation) was assessed. Results: A total of 32 individuals (9.4%) from the cohort were prescribed clozapine. The mean time to clozapine trial was 2.1 years (SD 1.95; range 0.17–6.25). The mean number of adequate trials of antipsychotic prior to starting clozapine was 2.74 (SD 1.13; range 1–5). Following clozapine initiation, mean hospital admissions per year reduced from 2.3 to 0.3 ( p=0.00). Mean hospital days pre- and post-clozapine also reduced (147 vs. 53; p=0.00). In total, 18 patients discontinued clozapine use during follow-up – 5 temporarily and 13 permanently. Conclusions: Patients are being prescribed clozapine earlier than previously demonstrated, though delays are still evident, and many patients discontinue treatment. More work needs to be undertaken to understand and address factors which lead to its discontinuation.

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Reasons for clozapine discontinuation in patients with treatment-resistant schizophrenia

Cited by 33 publications

References 23 publications

Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis

Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis

Adherence to clozapine vs. other antipsychotics in schizophrenia

Clozapine use – has practice changed?

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