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

Luykx, Jurjen J.; Stam, Noraly; Tanskanen, Antti; Tiihonen, Jari; Taipale, Heidi

doi:10.1192/bjp.2019.267

Cited by 34 publications

(44 citation statements)

References 27 publications

(46 reference statements)

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“…Quetiapine could be frequently initiated due to the favorable side‐effect profile, compared with other antipsychotics 37 . The findings are also in line with a recent Finnish registry study showing that restarting clozapine and switching to oral olanzapine is associated with a lower risk of psychiatric ward re‐admission, treatment failure, and mortality, compared with switching to other antipsychotics 23 …”

Section: Discussionsupporting

confidence: 76%

“…37 The findings are also in line with a recent Finnish registry study showing that restarting clozapine and switching to oral olanzapine is associated with a lower risk of psychiatric ward re-admission, treatment failure, and mortality, compared with switching to other antipsychotics. 23 We found that polypharmacy without clozapine was associated with similar persistence relative to monotherapy in patients discontinuing clozapine. Polypharmacy may reduce symptoms more effectively than monotherapy due to better receptor occupancy, but this could also lead to more or relatively severe side effects, resulting in no difference in persistence.…”

Section: Discussionmentioning

confidence: 66%

“…Due to the lack of studies on these strategies, current guidelines do not provide a clear answer as to which of those treatment options is preferred in patients who discontinue their treatment with clozapine 12,13 . However, a recent Finnish registry study showed that re‐initiation of clozapine and switching to oral olanzapine was associated with a lower risk of psychiatric rehospitalization, treatment failure, and mortality compared with switching to other antipsychotics in patients discontinuing clozapine 23 . Because those results are based on a single cohort in one country using those outcome measures, we reasoned it is worthwhile to evaluate if these antipsychotics are also preferred when looking at other outcome measures and in other countries, such as persistence of use in The Netherlands.…”

mentioning

confidence: 99%

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Persistence of Antipsychotic Use After Clozapine Discontinuation: A Real‐World Study Across Antipsychotics

Stam

Taipale

Tanskanen

et al. 2020

Clinical Translational Sci

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Although clozapine treatment is often discontinued due to limited efficacy or low tolerability, there is a lack of guidelines and evidence on treatment options after discontinuation of clozapine in patients with schizophrenia. Persistence has proven to be an adequate indicator for treatment effectiveness in patients with schizophrenia. The aim of this study was, therefore, to compare persistence of antipsychotic use between antipsychotic treatment options in patients after stopping clozapine treatment. Registry data from a prescription database representative of the Dutch population (1996-2017) was collected to investigate persistence in patients with schizophrenia who had been using clozapine for ≥ 90 days. Persistence with antipsychotics after clozapine discontinuation was analyzed using Cox-proportional hazard regression models. Our study population consisted of 321 participants, of whom 138 re-initiated clozapine and 183 started some other antipsychotic in the year after clozapine discontinuation (N = 518 antipsychotic use periods, N = 9,178 months). Second-generation antipsychotics (SGAs) as a group were associated with better persistence compared to first-generation antipsychotics (adjusted hazard ratio (aHR), 0.73; 95% confidence interval (CI) 0.57-0.93; P = 0.011). Compared with other antipsychotics, the following oral monotherapy antipsychotics were associated with significantly better persistence: restarting clozapine (aHR 0.48; 95% CI 0.32-0.71; P < 0.001) and switching to risperidone (aHR 0.52; 95% CI 0.32-0.84; P = 0.008) or olanzapine (aHR 0.55; 95% CI 0.35-0.87; P = 0.010). Sensitivity analyses confirmed the results. In conclusion, oral SGAs are associated with better persistence than alternative antipsychotic treatment options in patients discontinuing clozapine for undefined reasons. Especially clozapine (except in those with previous serious adverse reactions to clozapine), olanzapine and risperidone should be considered as oral monotherapy for these patients.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 66%

mentioning

confidence: 99%

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Persistence of Antipsychotic Use After Clozapine Discontinuation: A Real‐World Study Across Antipsychotics

Stam

Taipale

Tanskanen

et al. 2020

Clinical Translational Sci

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“…83,84 It is recognized that the best treatment for psychosis after clozapine has been discontinued is a repeated trial of clozapine. 85 Given the risks associated with treatment failure in our patient group, we took an active approach to supporting neutrophil counts, often using G-CSF.…”

Section: Discussionmentioning

confidence: 99%

“… 83 , 84 It is recognized that the best treatment for psychosis after clozapine has been discontinued is a repeated trial of clozapine. 85 …”

Section: Discussionmentioning

confidence: 99%

Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital

Silva

Higgins

Hammer

et al. 2021

Therapeutic Advances in Psychopharmacology

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Objective: Clozapine remains the most effective intervention for treatment resistant schizophrenia; however, its use is prohibited following neutropenias. We review neutrophil biology as applied to clozapine and describe the strategies to initiate clozapine following neutropenia used in a case series of 14 consecutive patients rechallenged in a United Kingdom (UK) high-secure psychiatric hospital. We examine outcomes including the use of seclusion and transfer. Methods: A case series of 14 male patients with treatment resistant schizophrenia treated with clozapine despite previous episodes of neutropenia between 2006 and 2015 is presented. Data were collected during 2015 and 2019. Using this routinely collected clinical data, we describe the patient characteristics, causes of neutropenia, the strategies used for rechallenging with clozapine and clinical outcomes. Results: Previous neutropenias were the result of benign ethnic neutropenia, clozapine, other medications and autoimmune-related. Our risk mitigation strategies included: granulocyte-colony stimulating factor (G-CSF), lithium and watch-and-wait. There were no serious adverse events; at follow up half of the patient’s had improved sufficiently to transfer them to conditions of lesser security. There were dramatic reductions in the use of seclusion. Conclusion: Even in this extreme group, clozapine can be safely and effectively re/initiated following neutropenias, resulting in marked benefits for patients. This requires careful planning based on an understanding of neutrophil biology and the aetiology of the specific episode of neutropenia.

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Schizophrenia and Related Psychoses

2021

The Maudsley Prescribing Guidelines in Psychiatry

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Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenialike symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuroimaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with agematched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

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

Cited by 34 publications

References 27 publications

Persistence of Antipsychotic Use After Clozapine Discontinuation: A Real‐World Study Across Antipsychotics

Persistence of Antipsychotic Use After Clozapine Discontinuation: A Real‐World Study Across Antipsychotics

Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital

Schizophrenia and Related Psychoses

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