Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia

Iruretagoyena, Bárbara; Castañeda, Carmen; Mena, Cristián; Díaz, Camila; Nachar, Rubén; Ramírez-Mahaluf, Juan Pablo; González-Valderrama, Alfonso; Undurraga, Juan; MacCabe, James H.; Crossley, Nicolás

doi:10.1016/j.schres.2021.07.024

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…Finally, we found no significant difference in discontinuation rate or in the time until discontinuation due to clozapine side effects between older and younger adults. This is in contrast to studies in younger adults, where older age predicted all‐cause discontinuation of clozapine 24–26 . Unlike our study, the only study that did include older adults did not correct for clozapine dose and comedication of other psychotropic drugs.…”

Section: Discussioncontrasting

confidence: 94%

“…This is in contrast to studies in younger adults, where older age predicted all-cause discontinuation of clozapine. [24][25][26] discontinued treatment within 5 years of observation. 17 14 patients died (also not directly linked to treatment), and 12 patients stopped treatment because of side effects, such as leukopenia and cardiac problems.…”

Section: Groenewald and Kokmentioning

confidence: 99%

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Side effects of clozapine in older adults with treatment‐resistant schizophrenia compared to younger adults

Groenewald,

Kok

2024

Int J Geriat Psychiatry

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ObjectivesTo study the differences in side effects of clozapine between older adults aged ≥55 years and younger adults aged 18–55 years with treatment‐resistant schizophrenia.MethodsA retrospective cohort study in a large mental health institute in the Netherlands. All patients diagnosed with treatment‐resistant schizophrenia who started with clozapine between 2011 and 2020 (N = 284) were included. We compared the number and type of side effects reported in the electronic patient files as well as the number of treatment discontinuations and the time until discontinuation, both due to side effects, of older adults versus younger adults.ResultsIn the younger age group (N = 183), the number of reported side effects was significantly higher in the first 3 months of treatment (Mann–Whitney U = 7341.5, p = 0.004) and after those 3 months (Mann–Whitney U = 5668.5, p < 0.001) compared with the number reported in the older age group (N = 101). Sedation, hypersalivation, dizziness, tachycardia, heartburn, nausea, weight gain, and constipation were reported significantly more often in the younger age group, and only extrapyramidal symptoms were reported significantly more often in the older age group. There was no significant difference in the number of treatment discontinuations due to side effects (23% vs. 21.8%, Chi‐2 = 0.051, df = 1, p = 0.821) and time until discontinuation due to side effects (b = 0.091, SE = 0.335, p = 0.798) between younger and older adults.ConclusionsSide effects of clozapine were reported significantly less often in older patients compared with younger patients. Older patients did not discontinue treatment due to side effects more often or earlier than younger patients. Older patients with schizophrenia may not be more vulnerable to side effects than younger adults.

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Section: Discussioncontrasting

confidence: 94%

Section: Groenewald and Kokmentioning

confidence: 99%

Side effects of clozapine in older adults with treatment‐resistant schizophrenia compared to younger adults

Groenewald,

Kok

2024

Int J Geriat Psychiatry

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“…All-cause clozapine discontinuation was not signi cantly associated with delayed clozapine initiation, only with the age at which clozapine was initiated. A national database study in Chile reported that an older age at clozapine initiation and delayed clozapine initiation are associated with clozapine discontinuation [22]; our results are partly consistent. Because clozapine is considered the last treatment option, the probability of switching to other antipsychotics is low.…”

Section: Discussionsupporting

confidence: 83%

Long-term outcomes of delayed clozapine initiation in treatment-resistant schizophrenia: A multicenter retrospective cohort study

Hatano

Kamei

Takeuchi³

et al. 2023

Preprint

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Background Clozapine is the only antipsychotic medication with proven efficacy against treatment-resistant schizophrenia. This multicenter retrospective cohort study aimed to evaluate the impact of a delay in clozapine initiation on long-term outcomes. Methods Patients who initiated clozapine treatment between July 2009 and December 2018 were included in this study. According to the length of time from the diagnosis of schizophrenia to the clozapine initiation, the patients were categorized into one of three groups: early (≤ 9 years), intermediate (10–19 years), and late (≥ 20 years) initiation. The endpoints were psychiatric rehospitalization, all-cause clozapine discontinuation, and treatment failure at 3 years. Hazard ratios (HR) and 95% confidence interval (CI) were estimated using the Fine and Gray method or the Cox proportional hazards model. Results The incidence rates of rehospitalization at 3 years according to the cumulative incidence function were 32.3% for early, 29.7% for intermediate, and 62.2% for late initiation, respectively. Late initiation had a significantly higher risk of rehospitalization than both early (HR, 2.94; 95% CI, 1.01– 8.55; P = 0.016 by the Gray's test) and intermediate initiation (HR, 3.13; 95% CI, 1.34–7.30; P = 0.0025 by the Gray's test). The incidence rate of all-cause clozapine discontinuation at 3 years using the Kaplan–Meier method were 13.0% for early, 10.6% for intermediate, and 20.1% for late initiation. The risk of all-cause clozapine discontinuation was not significantly among the groups. The late initiation group showed significantly increased risk of treatment failure only when using univariate analysis. The late initiation group had more patients discontinuing because of death due to physical diseases than the other groups. Conclusions The study suggests that clozapine should be initiated promptly in patients with treatment-resistant schizophrenia to prevent psychiatric rehospitalization during long-term treatment. Further studies of higher quality, with appropriate consideration of patient characteristics, and with larger sample sizes are needed.

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“…The primary outcome was an all-cause discontinuation rate between the once-daily and divided dosing regimen groups, which is the real-world outcome in schizophrenia. 12,13 Reasons for discontinuation were assessed from case notes in outpatient medical records and classified as: (1) lack of efficacy, defined as an inadequate response to clozapine treatment; (2) adverse drug reactions, defined as any adverse effects attributed to clozapine and leading to intolerability; (3) patient decision, defined as patient declining to take clozapine, patient believing that clozapine was not required, or nonadherence not otherwise specified; or (4) other reasons. The secondary outcomes, which were compared between the once-daily and divided dosing regimen groups, included hospitalization, time to discontinuation, time to hospitalization (time to exacerbation of psychiatric symptoms that required treatment at the inpatient unit), adverse events (any reported adverse events regardless of clozapine discontinuation), and nonadherence.…”

Section: Methodsmentioning

confidence: 99%

Section: Outcome Measuresmentioning

confidence: 99%

Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily and Divided Dosing Regimen in Patients With Treatment-Resistant Schizophrenia

Sathienluckana,

Jansing,

Srisuriyakamon

et al. 2023

Ann Pharmacother

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Background: Clozapine is the most effective antipsychotic with respect to the incidence of discontinuation and is indicated for treatment-resistant schizophrenia. Although the recommendation for clozapine administration is divided dosing, once-daily dosing of clozapine is commonly prescribed in many countries. However, there is currently no clinical data comparing all-cause discontinuation between the 2 methods of administration of clozapine. Objectives: To compare the all-cause discontinuation and safety of clozapine administration between once-daily and divided dosing regimens. Methods: This was a retrospective cohort study. Participants were patients with treatment-resistant schizophrenia who had received 300 to 600 mg/day of clozapine for at least 3 months. Data were collected from outpatient medical records at Somdet Chaopraya Institute of Psychiatry. Eligible patients were classified into 2 groups: once-daily dosing and divided dosing. The primary outcome was the all-cause discontinuation rate between groups. The duration of the study was 2 years. Results: One hundred eighteen patients were included and analyzed in this study (once-daily dosing group: n = 58; divided dosing group: n = 60). There was no significant difference in all-cause discontinuation between the 2 groups (odds ratio 1.03; 95% confidence interval: [0.28, 3.79]: P = 1.00), or adverse events between groups. Conclusion and Relevance: In patients with treatment-resistant schizophrenia, there were no significant differences in effectiveness or safety between once-daily and divided dosing of clozapine. Further prospective studies with larger sample sizes are required to confirm these findings.

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Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia

Cited by 8 publications

References 42 publications

Side effects of clozapine in older adults with treatment‐resistant schizophrenia compared to younger adults

Side effects of clozapine in older adults with treatment‐resistant schizophrenia compared to younger adults

Long-term outcomes of delayed clozapine initiation in treatment-resistant schizophrenia: A multicenter retrospective cohort study

Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily and Divided Dosing Regimen in Patients With Treatment-Resistant Schizophrenia

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Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia

Cited by 8 publications

References 42 publications

Side effects of clozapine in older adults with treatment‐resistant schizophrenia compared to younger adults

Side effects of clozapine in older adults with treatment‐resistant schizophrenia compared to younger adults

Long-term outcomes of delayed clozapine initiation in treatment-resistant schizophrenia: A multicenter retrospective cohort study

Comparison of the Effectiveness and Safety of Clozapine Between Once-Daily and Divided Dosing Regimen in Patients With Treatment-Resistant Schizophrenia

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Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia