Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study

Schneider, Carolina; Papachristou, Efstathios; Wimberley, Theresa; Gasse, Christiane; Dima, Danai; MacCabe, James H.; Mortensen, Preben Bo; Frangou, Sophia

doi:10.1016/j.euroneuro.2015.02.003

Cited by 43 publications

(40 citation statements)

References 37 publications

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“…Our findings are consistent with the recent Scandinavian population study that found that 88.8% of EOS patients (mean age of onset is 16.2 years) prescribed clozapine appeared to have a favorable outcome as indicated by continued prescription redemption for 6 consecutive months (Schneider et al 2015).…”

Section: Discussionsupporting

confidence: 82%

“…Periods shorter than this may reflect discontinuation caused by adverse drug reactions during titration, whereas discontinuation after 6 months is likely to be influenced by nonspecific factors affecting long-term adherence, including refusal of ongoing hematological monitoring (Schneider et al 2015). Additionally, symptomatic improvement may continue from 6 weeks to ‡6 months.…”

Section: Discussionmentioning

confidence: 99%

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Strong Treatment Response and High Maintenance Rates of Clozapine in Childhood-Onset Schizophrenia

Kasoff

Ahn

Gochman

et al. 2016

Journal of Child and Adolescent Psychopharmacology

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Objective: Childhood-onset schizophrenia (COS) is a rare but severe form of the disorder, which is often treatment refractory. Short-term studies have indicated a greater differential efficacy, evident through effect sizes, favoring clozapine over other agents in alleviating negative symptoms in COS patients compared with adult-onset patients (AOS). There have been no data for COS patients on long-term compliance with clozapine treatment. Therefore, we wanted to know, over a span of up to 24 years, how many of our COS cohort had remained on clozapine for at least 2 years. We review short-term treatment data and present updated long-term data on compliance and functioning for our patients. Methods: We present the results for long-term medication maintenance over a 24 year observation period for our cohort of 131 patients. Of this cohort, 91.6% (120) were available for follow-up information from either in-person or telephone contact with the patient and/or family members. We defined clozapine compliance as ‡2 years receiving this medication and doing well. Results: We were able to contact 120 of the 131 patients. In spite of the additional cost and inconvenience of regular blood monitoring, 87 patients (72.5%, 87/120) adhered to long-term clozapine maintenance therapy with dosages ranging from 50 to 900 mg, and a median dosage of 500 mg. This rate exceeds the long-term clozapine maintenance rates reported for AOS patients. Conclusions: Short-term data on differential efficacy and long-term maintenance data suggest a possibly greater efficacy of clozapine, relative to other antipsychotics, in COS than in AOS. Our overall findings indicate that very early-onset schizophrenic patients may be more responsive to clozapine. This extends other support for clozapine as an option in the treatment of early-onset schizophrenia.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Strong Treatment Response and High Maintenance Rates of Clozapine in Childhood-Onset Schizophrenia

Kasoff

Ahn

Gochman

et al. 2016

Journal of Child and Adolescent Psychopharmacology

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“…Third, we restricted the cohort to adult individuals (≥18 years at first diagnosis of schizophrenia) since the antipsychotic treatment guidelines as well as clinical prescribing practice and response to antipsychotics differ between childhood-and adultonset schizophrenia. 31,32 Finally, all analyses were repeated with polygenic risk scores calculated based on SNPs selected using thresholds of p<0.01 and p<0.1, including 10,622 and 35,792 SNPs, respectively.…”

Section: Discussionmentioning

confidence: 99%

Polygenic Risk Score for Schizophrenia and Treatment-Resistant Schizophrenia

Wimberley

Gasse

Meier

et al. 2017

Schizophrenia Bulletin

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Treatment-resistant schizophrenia (TRS) affects around one third of individuals with schizophrenia.Although a number of socio-demographic and clinical predictors of TRS have been identified, data on the genetic risk of TRS are sparse. We aimed to investigate the association between the polygenic risk score for schizophrenia and treatment resistance in patients with schizophrenia. We conducted a nationwide, population-based follow-up study among all Danish individuals born after 1981 and with an incident diagnosis of schizophrenia between 1999 and 2007. Based on genome-wide data polygenic risk scores for schizophrenia were calculated in 862 individuals with schizophrenia. TRS was defined as either clozapine initiation or at least two periods of different antipsychotic monotherapies and still being hospitalized. We estimated hazard rate ratios (HRs) for TRS in relation to the polygenic risk score while adjusting for population stratification, age, sex, geographical area at birth, clinical treatment setting, psychiatric comorbidity, and calendar year. Among the 862 individuals with schizophrenia, 181 (21.0%) met criteria for TRS during 4,674 person-years of follow-up. We found no significant association between the polygenic risk score and TRS, adjusted HR = 1.13 (95% CI: 0.95-1.35). Based on these results, the use of the polygenic risk score for schizophrenia to identify individuals with TRS is at present inadequate to be of clinical utility at the individual patient level. Future research should include larger genetic samples in combination with nongenetic markers. Moreover, a TRS-specific developed polygenic risk score would be of great interest towards early prediction of TRS.

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“…Previous studies investigating risk factors for TR have utilised clozapine prescription rates as a proxy measure of TR ( (Nielsen et al, 2012b, Schneider et al, 2015, Stroup et al, 2014, however, given the underutilisation of clozapine in clinical practice, such studies do not measure all people with TR. Although, a few potential risk factors for treatment resistance (TR), such as poor premorbid functioning, living in less urban areas, comorbid personality disorder, longer duration of untreated psychosis (DUP), greater severity of negative symptoms, and a younger age of illness onset have been suggested (Frank et al, 2015, Martin and Mowry, 2016, Meltzer, 1997, Ortiz et al, 2013, Schennach et al, 2012, Vanelle et al, 1994, Wimberley et al, 2016, the predictive value of specific clinical and demographic factors on treatment resistance in first episode schizophrenia has not yet been widely investigated (Lin et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses

et al. 2016

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BackgroundClozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.MethodThis is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.ResultsSeventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).ConclusionsFor the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

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Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study

Cited by 43 publications

References 37 publications

Strong Treatment Response and High Maintenance Rates of Clozapine in Childhood-Onset Schizophrenia

Strong Treatment Response and High Maintenance Rates of Clozapine in Childhood-Onset Schizophrenia

Polygenic Risk Score for Schizophrenia and Treatment-Resistant Schizophrenia

Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses

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