Clozapine Rechallenge After Major Adverse Effects: Clinical Guidelines Based on 259 Cases

Manu, Peter; Lapitskaya, Yevgeniya; Shaikh, Atef; Nielsen, Jimmi

doi:10.1097/mjt.0000000000000715

Cited by 71 publications

(68 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On a general note, neutropenia is a more common reason for clozapine discontinuation than agranulocytosis, and about 50% of patients with previous neutropenia tolerate clozapine rechallenge. 26 Whenever clozapine seems the only viable antipsychotic treatment option in patients with schizophrenia, adding lithium may increase neutrophil counts, but recently authors have cautioned against lithium discontinuation in such patients. 27 If clinicians are concerned about past or future serious adverse drug reactions in a specific patient previously on clozapine, several good treatment options other than clozapine remain, based on our data.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In some cases, clozapine may even be re-trialled after certain life-threatening AEs that necessitated stopping the drug. 41 …”

Section: Adverse Events On Clozapinementioning

confidence: 99%

Clozapine in the treatment of refractory schizophrenia: a practical guide for healthcare professionals

Flanagan

Lally

Gee

et al. 2020

British Medical Bulletin

View full text Add to dashboard Cite

Background Clozapine remains the only medication licensed for treating refractory schizophrenia. However, it remains underutilized in part due to concerns regarding adverse events. Sources of data Published literature. Areas of agreement Common adverse events during clozapine treatment include sedation, hypersalivation, postural hypotension, dysphagia, gastrointestinal hypomotility, weight gain, diabetes mellitus and dyslipidaemia. Rare but serious events include agranulocytosis, cardiomyopathy, myocarditis, pneumonia, paralytic ileus and seizure. Areas of controversy It remains unclear how best to minimize clozapine-induced morbidity/mortality (i) during dose titration, (ii) from hypersalivation and (iii) from gastrointestinal hypomotility. It is also unclear how clozapine pharmacokinetics are affected by (i) gastrointestinal hypomotility, (ii) systemic infection and (iii) passive exposure to cigarette smoke. Whether monthly haematological monitoring needs to continue after 12 months of uninterrupted therapy is also a subject of debate. Growing points There is a need for better management of serious clozapine-related adverse events in addition to agranulocytosis. There is also a need for better education of patients and carers, general practitioners, A&E and ITU staff and others of the problems posed in using clozapine safely. Areas timely for developing research There is a need for more research on assessing clozapine dosage (i) as patients get older, (ii) with respect to exposure to cigarette smoke and (iii) optimizing response if adverse events or other factors limit dosage.

show abstract

“…The existing best evidence is derived from a small number of nationwide pharmacovigilance studies reporting crude outcomes on clozapine rechallenge in combination with individual case reports and series that will inevitably be affected by publication bias. These have been subject to meta-analysis [1]. The evidence relating to the use of drugs to support neutrophil counts is derived from case reports and series only.…”

Section: General Warningmentioning

confidence: 99%

Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

et al. 2020

View full text Add to dashboard Cite

Clozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.

show abstract

Clozapine Rechallenge After Major Adverse Effects: Clinical Guidelines Based on 259 Cases

Cited by 71 publications

References 72 publications

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

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

Clozapine in the treatment of refractory schizophrenia: a practical guide for healthcare professionals

Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

Contact Info

Product

Resources

About