Clozapine tolerability in Treatment Resistant Schizophrenia: exploring the role of sex

Martini, Francesca; Spangaro, Marco; Buonocore, Mariachiara; Bechi, Margherita; Cocchi, Federica; Guglielmino, Carmelo; Bianchi, Laura; Sapienza, Jacopo; Agostoni, Giulia; Mastromatteo, Antonella Rita; Bosia, Marta; Cavallaro, Roberto

doi:10.1016/j.psychres.2020.113698

Cited by 11 publications

(13 citation statements)

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“…Accordingly, most of the evidence on gender differences in side effects of clozapine relates to metabolic disturbances[ 122 ]. However, findings are not consistent, and both genders appear to have increased risk of metabolic syndrome in different reports[ 122 , 126 - 128 ]. Hypertension, elevated triglycerides, lower high-density lipoprotein levels, and cardiac abnormalities appear to be more common in men[ 122 ].…”

Section: Preventing Resistance To Clozapine Treatmentmentioning

confidence: 95%

“…Women are more likely to develop hyperglycaemia and diabetes and increases in weight and body mass index[ 122 , 126 ]. There is very little evidence of gender differences in other side effects, though certain studies have found haematological abnormalities and constipation to be commoner among women[ 122 , 125 , 128 , 129 ].…”

Section: Preventing Resistance To Clozapine Treatmentmentioning

confidence: 99%

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Clozapine resistant schizophrenia: Newer avenues of management

Chakrabarti¹

2021

WJP

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About 40%-70% of the patients with treatment-resistant schizophrenia have a poor response to adequate treatment with clozapine. The impact of clozapine-resistant schizophrenia (CRS) is even greater than that of treatment resistance in terms of severe and persistent symptoms, relapses and hospitalizations, poorer quality of life, and healthcare costs. Such serious consequences often compel clinicians to try different augmentation strategies to enhance the inadequate clozapine response in CRS. Unfortunately, a large body of evidence has shown that antipsychotics, antidepressants, mood stabilizers, electroconvulsive therapy, and cognitive-behavioural therapy are mostly ineffective in augmenting clozapine response. When beneficial effects of augmentation have been found, they are usually small and of doubtful clinical significance or based on low-quality evidence. Therefore, newer treatment approaches that go beyond the evidence are needed. The options proposed include developing a clinical consensus about the augmentation strategies that are most likely to be effective and using them sequentially in patients with CRS. Secondly, newer approaches such as augmentation with long-acting antipsychotic injections or multi-component psychosocial interventions could be considered. Lastly, perhaps the most effective way to deal with CRS would be to optimize clozapine treatment, which might prevent clozapine resistance from developing. Personalized dosing, adequate treatment durations, management of side effects and non-adherence, collaboration with patients and caregivers, and addressing clinician barriers to clozapine use are the principal ways of ensuring optimal clozapine treatment. At present, these three options could the best way to manage CRS until research provides more firm directions about the effective options for augmenting clozapine response.

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Section: Preventing Resistance To Clozapine Treatmentmentioning

confidence: 95%

Section: Preventing Resistance To Clozapine Treatmentmentioning

confidence: 99%

Clozapine resistant schizophrenia: Newer avenues of management

Chakrabarti¹

2021

WJP

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“…It is illegal to post this copyrighted PDF on any website. e1 J Clin Psychiatry 82:5, September/October 2021 Brief Report C lozapine, the only antipsychotic medication approved for treatment-resistant schizophrenia, 1 was recently reported to be associated with increased risk of COVID-19 infection in patients with schizophrenia spectrum disorders. 2 Additionally, a history of military service has been associated with increased risk of testing positive for COVID-19.…”

mentioning

confidence: 99%

Clozapine Is Associated With Higher COVID-19 Infection Rate in Veterans With Schizophrenia or Schizoaffective Disorder

Okusaga

Mitchell

Bernard

et al. 2021

J. Clin. Psychiatry

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“…However, in two recent investigations, BMI increase predicted an improved outcome in terms of both positive and negative symptoms [ 45 , 46 ], which was inconsistent with the current findings. Weight gain might be a possible side effect resulting from clozapine treatment rather than reflecting an improved response [ 47 ]. Other demographic data such as sex and smoking were not identified as a significant predictor of clozapine response [ 34 , 48 , 49 ], despite having a significant effect on clozapine concentrations [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Other demographic data such as sex and smoking were not identified as a significant predictor of clozapine response [ 34 , 48 , 49 ], despite having a significant effect on clozapine concentrations [ 12 ]. However, there were considerable differences to address in terms of clozapine tolerability between males and females [ 47 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine

et al. 2021

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Clozapine remains the drug of choice for resistant schizophrenia. However, its dose-response relationship is still controversial. The current investigation aimed to develop a repeated time-to-positive symptoms improvement following the onset of clozapine treatment in Malaysian schizophrenia spectrum disorder patients. Data from patients’ medical records in the Psychiatric Clinic, Penang General Hospital, were retrospectively analyzed. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.3.0). Kaplan–Meier-visual predictive check (KM-VPC) and sampling-importance resampling (SIR) methods were used to validate the final model. A total of 116 patients were included in the study, with a mean follow-up of 306 weeks. Weibull hazard function best fitted the data. The hazard of positive symptoms improvement decreased 4% for every one-year increase in age over the median of 41 years (adjusted hazard ratio (aHR), 0.96; 95% confidence intervals (95% CI), (0.93–0.98)). However, patients receiving a second atypical antipsychotic agent had four-folds higher hazard (aHR, 4.01; 95% CI, (1.97–7.17)). The hazard increased 2% (aHR, 1.02; 95% CI, (1.01–1.03)) for every 1 g increase in the clozapine six months cumulative dose over the median of 34 g. The developed model provides essential information on the hazard of positive symptoms improvement after the first clozapine dose administration, including modifiable predictors of high clinical importance.

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Clozapine tolerability in Treatment Resistant Schizophrenia: exploring the role of sex

Cited by 11 publications

References 50 publications

Clozapine resistant schizophrenia: Newer avenues of management

Clozapine resistant schizophrenia: Newer avenues of management

Clozapine Is Associated With Higher COVID-19 Infection Rate in Veterans With Schizophrenia or Schizoaffective Disorder

A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine

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