Is the Time Course of Clozapine Response Correlated to the Time Course of Clozapine Plasma Levels? A One-Year Prospective Study in Drug-Resistant Patients with Schizophrenia

Fabrazzo, Michele; Pia, Silvestro La; Monteleone, Palmiero; Esposito, Giuseppina; Pinto, Antonio; Simone, Luigi De; Bencivenga, R.; Maj, Mario

doi:10.1016/s0893-133x(02)00319-6

Cited by 48 publications

(24 citation statements)

References 31 publications

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“…Most researchers find that a threshold plasma level of 350-420 ng/ml of CLZ is associated with an increased probability of a good clinical response to the drug. Moreover, much of the reviewed data indicate that increasing the oral CLZ dose in non responder patients to achieve a plasma level of at least 350-420 ng/ml can increase the number of CLZ responders (Potkin et al, 1994[121]; Fabrazzo et al, 2002[48]; Mauri et al, 2007[97]). Plasma CLZ concentrations (and the probability of reaching a given threshold) may be influenced by many factors such as age, gender and smoking (Schulte, 2003[130]).…”

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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Therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding side effects by maintaining long-term exposure to minimally effective blood concentrations. The rationale for using therapeutic drug monitoring in relation to second-generation antipsychotics is still being discussed at least with regard to the real clinical utility, but there is evidence that it can improve efficacy, especially when patients do not respond or develop side effects using therapeutic doses. Furthermore, drug plasma concentration determinations can be of some utility in medico-legal problems. This review concentrates on the clinical pharmacokinetic data related to clozapine, risperidone, paliperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole, sertindole, asenapine, iloperidone, lurasidone, brexpiprazole and cariprazine and briefly considers the main aspects of their pharmacodynamics. Optimal plasma concentration ranges are proposed for clozapine, risperidone, paliperidone and olanzapine because the studies of quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information and there is no direct evidence concerning ziprasidone, aripiprazole, sertindole, brexpiprazole and cariprazine: the few reported investigations need to be confirmed and extended.

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Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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“…Dose is significantly correlated with plasma levels of clozapine and NDMC (P=0.01-0.001) but not, as noted above, with the NDMC/clozapine ratio. This provides further evidence that the absolute levels of clozapine and NDMC, while important in identifying responders and non-responders (Fabrazzo et al 2002) are Table 3 Serum N-desmethylclozapine levels and clinical response in schizophrenia. Statistical analysis of the correlation between clinical outcome and serum levels of clozapine and N-desmethylclozapine (NDMC) for a cohort of 92 clozapine treated schizophrenics are reported.…”

Section: Resultsmentioning

confidence: 72%

The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine

et al. 2004

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“…A number of studies have recommended trial durations of between 4 and 12 months (66–68). Others, however, have suggested that the time course of response is not significantly different to non-clozapine antipsychotics (69–71), and the perception of a delayed response may primarily be due to the time taken to reach a therapeutic level (72). Due to the lack of clarity as to where to proceed following a failed clozapine trial, and the clinical effort required to establish treatment with clozapine, we recommend clozapine therapy should be tried for a duration of at least 3 months following attainment of therapeutic plasma levels.…”

Section: Resultsmentioning

confidence: 99%

Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

Howes

McCutcheon

Agid

et al. 2017

AJP

824

702

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Objective Treatment resistance complicates the management of schizophrenia. Research and clinical translation is limited by inconsistent definitions. To address this we evaluated current approaches and then developed consensus criteria and guidelines. Method A systematic review of randomized antipsychotic clinical trials in treatment resistant schizophrenia was performed. Definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed by a working group of researchers and clinicians through i) a multi-phase, mixed methods approach; ii) identifying key criteria via an online survey; and iii) meetings to achieve consensus. Results 42 studies met inclusion criteria. Of these, 21 (50%) studies did not provide operationalized criteria, whilst in others, criteria varied considerably, particularly regarding symptom severity, prior treatment duration and antipsychotic dose thresholds. Important for the inability to compare results, only two (5%) studies utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) ≥moderate functional impairment; 3) prior treatment consisting of ≥2 different antipsychotic trials, each for a minimum duration and dose; 4) adherence systematically assessed and meeting minimum criteria; 5) ideally at least one prospective treatment trial; 6) criteria that clearly separated responsive from treatment resistant patients. Conclusions There is considerable variation in current approaches to defining treatment resistance in schizophrenia. We present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment and treatment response in schizophrenia, providing a benchmark for research and clinical translation.

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Is the Time Course of Clozapine Response Correlated to the Time Course of Clozapine Plasma Levels? A One-Year Prospective Study in Drug-Resistant Patients with Schizophrenia

Cited by 48 publications

References 31 publications

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine

Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

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