Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia: a chart review study

Shah, Parita; Iwata, Yusuke; Brown, Eric E.; Kim, Julia; Sanches, Marcos; Takeuchi, Hiroyoshi; Nakajima, Shinichiro; Hahn, Margaret; Remington, Gary; Gerretsen, Philip; Graff‐Guerrero, Ariel

doi:10.1007/s00406-019-01053-6

Cited by 40 publications

(53 citation statements)

References 69 publications

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“…This corroborates the hypothesis that clozapine should be initiated as early as possible in patients with TRS, in order to reduce adverse outcomes. 26,27 As expected, clozapine use was significantly higher in TRS than in the treatment-responsive group. Many studies have demonstrated clozapine superiority in reducing positive and negative symptoms, as well as antipsychotic discontinuation.…”

Section: Discussionsupporting

confidence: 73%

Prevalence and predictors of treatment-resistant schizophrenia in a tertiary hospital in Northeast Brazil

Soares¹,

Carvalho²,

Ribeiro³

et al. 2021

Trends Psychiatry Psychother

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Objective: To investigate epidemiological factors related to treatment-resistant schizophrenia (TRS) in Northeast Brazil, a region where data about mental health are still scarce. Methods: This retrospective cross-sectional study included all patients with schizophrenia currently receiving treatment at the outpatient psychiatric clinic of a tertiary hospital in Northeast Brazil. They were divided into TRS and treatment-responsive groups, and epidemiological characteristics of both groups were compared. A logistic regression model investigated factors related to treatment resistance. Results: Two hundred and five patients were included, 155 treatment-resistant and 50 treatmentresponsive. The TRS group had higher use of benzodiazepines (36.1 vs. 18%, p = 0.017) and antiepileptics (36.8 vs. 8.0%, p < 0.001), antipsychotic polypharmacy (28.6 vs. 8%, p = 0.003) and suicide attempts (35.6 vs. 20%, p = 0.04). Age at onset was younger (19.7±7.3 vs. 24.6±8.6 years, p = 0.001) and CGI was higher in TRS (3.72±1.00 vs. 3.16±1.00, p = 0.001). In logistic regression, being married was a protector (odds ratio [OR] = 0.248, 95% confidence interval [95%CI] 0.091-0.679, p = 0.007) and younger age at onset was a predictor (OR = 1.076, 95%CI 1.034-1.120, p < 0.001) of treatment resistance. Conclusion:Early onset of disease was associated with more treatment resistance, while being married with less resistance. Clinicians should identify early predictors of resistance in order to reduce unfavorable outcomes.

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Section: Discussionsupporting

confidence: 73%

Prevalence and predictors of treatment-resistant schizophrenia in a tertiary hospital in Northeast Brazil

Soares¹,

Carvalho²,

Ribeiro³

et al. 2021

Trends Psychiatry Psychother

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“…Üçok et al (2015) reported patients demonstrating the best response to clozapine response had fewer adequate antipsychotic trials before clozapine compared to those with minimal or no clinical response. Shah et al (2020) also found clozapine responders had fewer antipsychotic trials prior to clozapine initiation than clozapine non-responders, despite the duration of non-clozapine antipsychotic treatment not differing between groups. The fourth study reported no association between the number of antipsychotics trials prior to clozapine initiation and the net change in number or length of hospital admissions after clozapine was initiated (Gee et al, 2016).…”

Section: Resultsmentioning

confidence: 95%

“…Shah et al (2020) found clozapine responders had a significantly shorter delay in clozapine initiation than non-responders, and delay in clozapine initiation was a significant predictor of clozapine response in regression analysis. Here, age at clozapine initiation was not significantly associated with clozapine response and therefore unlikely to be driving this effect.…”

Section: Resultsmentioning

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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“…7) 이러한 견지에서 클로자핀 사용이 지연되면서 정신병 적 증상이 계속되는 환자들의 치료 반응 역시 나쁠 수 있다 는 가설이 제시되었고 몇몇 연구에서 이러한 경향이 확인된 바 있다. [26][27][28]…”

Section: 양소영 등unclassified

Effect of Delayed Clozapine Initiation on Acute Treatment Response in Treatment-Resistant Schizophrenia

Yang¹,

Choi²,

Park³

et al. 2021

Korean J Schizophr Res

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Objectives: Recent studies have reported that delayed initiation of clozapine can affect clinical response in patients with treatment-resistant schizophrenia (TRS). This study aimed to explore the relationship between delayed initiation of clozapine and acute treatment response. Methods: Sixty-five inpatients with TRS who started clozapine for the first time were included through a retrospective chart review. Acute treatment response was defined as a 30% reduction in the Positive and Negative Syndrome Scale score or a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) at 4 weeks after initiating clozapine. Results: After meeting the TRS criteria, the mean delay for initiating clozapine was approximately 13.8 months. The delay was shorter in patients who showed a better response to clozapine in logistic regression analysis (p=0.037). Conclusion: Our findings suggest that reducing the delay in initiating clozapine increases the effectiveness of clozapine in patients with TRS.

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Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia: a chart review study

Cited by 40 publications

References 69 publications

Prevalence and predictors of treatment-resistant schizophrenia in a tertiary hospital in Northeast Brazil

Prevalence and predictors of treatment-resistant schizophrenia in a tertiary hospital in Northeast Brazil

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

Effect of Delayed Clozapine Initiation on Acute Treatment Response in Treatment-Resistant Schizophrenia

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