Clozapine Levels After Clozapine Discontinuation

Leon, José de; Henighan, V.; Stanilla, Joseph K.; Simpson, George M.

doi:10.1097/00004714-199604000-00016

Cited by 17 publications

(12 citation statements)

References 3 publications

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“…At the hospital, the catatonic symptoms in the three episodes were definitely described between 10 and 18 days after sudden withdrawal of clozapine. After 1 week of sudden discontinuation of therapeutic serum clozapine concentrations, clozapine may disappear completely from the body [31]. …”

Section: Discussionmentioning

confidence: 99%

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

Bilbily

McCollum

Leon

2017

Case Reports in Psychiatry

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A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5). The Liverpool Adverse Drug Reaction (ADR) Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is described with three catatonic episodes which (1) occurred after sudden discontinuation of clozapine in the context of decades of follow-up, (2) had ≥3 of 12 DSM-5 catatonic symptoms and serum creatinine kinase elevation, and (3) required medical hospitalization and intravenous fluids. Clozapine may be a gamma-aminobutyric acid (GABA) receptor agonist; sudden clozapine withdrawal may explain a sudden decrease in GABA activity that may contribute to the development of catatonic symptoms in vulnerable patients. Based on the limited information from these cases, the pharmacological treatment for catatonia secondary to sudden clozapine withdrawal can include benzodiazepines and/or restarting clozapine.

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Section: Discussionmentioning

confidence: 99%

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

Bilbily

McCollum

Leon

2017

Case Reports in Psychiatry

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“…102 As the matter of fact, by using drug discontinuation in the clinical environment, the second author obtained a half-life of 17 hours in one patient and 34 hours in another. 104 Clozapine is lipophilic and deposits in the fat tissue 111 which explains the dramatic increase in clozapine half-life after repeated dosing. 109 In the clinical environment, the problem is the half-life that governs clozapine elimination after discontinuation is not average clozapine half-life, but rather the individual's clozapine half-life, which varies according to the metabolic characteristics of each patient.…”

Section: Clozapine Non-adherence and Clinical Relevancementioning

confidence: 99%

“…Moreover, clozapine is frequently used for both acute and maintenance treatments in these patients, making it perhaps the ideal drug for a study of antipsychotic non-adherence. In fact, clozapine has a peculiar pharmacodynamic 103 and pharmacokinetic profile, 104 and when patients who are consistently taking it decide to stop suddenly, this non-adherence can manifest with serious clozapine withdrawal syndromes including cholinergic rebound, 105 worsening of psychosis and motor symptoms, 106 or appearance of never-manifested symptoms such as catatonia. 107 …”

Section: Our Studies On Medication Adherence and On Antipsychotic Phamentioning

confidence: 99%

Section: Our Studies On Medication Adherence and On Antipsychotic Phamentioning

confidence: 99%

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<p>Self-Report for Measuring and Predicting Medication Adherence: Experts’ Experience in Predicting Adherence in Stable Psychiatric Outpatients and in Pharmacokinetics</p>

Cuevas

Leon

2020

PPA

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Poor adherence to appropriately prescribed medication is a global challenge for psychiatrists. Prior Studies: Measuring adherence is complicated. In our recent three-country naturalistic study including more than 1000 patients and their adherence to multiple medication prescriptions at the same time, patients' self-report of adherence to each specific drug was the only practical option for measuring adherence. Systematic literature reviews provide inconsistent results for sociodemographic, clinical and medication variables as predictors of adherence to psychiatric drugs. Our studies over the last 10 years in relatively stable psychiatric outpatients have shown that some self-reported health beliefs had consistent, strong effects and a better predictive role. Three dimensions of these health beliefs are characteristics of the individual: 1) attitudes toward psychiatric medication such as pharmacophobia (fear of taking drugs or medicines), 2) health locus of control (the belief patients have about who or what agent determines the state of their health), 3) psychological reactance (an emotional reaction in direct contradiction to rules or regulations that threaten or suppress certain freedoms in behavior). They can be measured by the Patient Health Beliefs Questionnaire on Psychiatric Treatment. The attitude toward each specific medication can be measured by the necessity-concern framework and summarized as the presence or absence of skepticism about that drug. After 25 years conducting pharmacokinetic studies in psychiatric drugs, particularly antipsychotics, we have limited understanding of how to use blood levels to predict the effects of non-adherence or to establish it. Expert Opinion on Future Studies: Future studies to predict adherence should include the inpatient setting and explore insight. Studying the pharmacokinetics associated with nonadherence in each psychiatric drug is a major challenge. Medication adherence is a complex and dynamic process changing over time in the same patient. Personalizing adherence using psychological or pharmacological variables are in their initial stages.

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“…As a matter of fact, in a dose-response double-blind clozapine study five patients out of 50 had serum clozapine concentrations >1000 ng/ml at least once without obvious manifestations of clozapine intoxication. 17 Therefore, many patients may have signs of clozapine intoxication with high TDMs but others appear to be very resistant to them and show no obvious signs of intoxication. Recently, a patient with a clozapine level >2000 ng/ml with no obvious manifestations of clozapine intoxication was identified during pneumonia.…”

Section: Recommended Measuring Crp If An Unexpectedly High Serum Clozmentioning

confidence: 99%

Two cases of high serum clozapine concentrations occurring during inflammation in Chinese patients

Ruan

Xiao-ling

Guo

et al. 2018

Int J Psychiatry Med

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Objective Serious infections or inflammations have been associated with serum clozapine concentration increases and sometimes with clozapine toxicity. Method These two cases describe Chinese patients (Case 1: a 57-year-old female nonsmoker with severe dermatitis and Case 2: a 47-year-old male nonsmoker with influenza and secondary infection). Results In both cases, the Drug Interaction Probability Scale established the presence of a probable drug-drug interaction. In both cases, the clozapine and the total clozapine concentration-to-dose ratios followed a temporal pattern (normal-high-normal), consistent with an inhibition of clozapine metabolism during peak inflammation. In the first case, the total clozapine concentration-to-dose ratio (8 with no/low inflammation: median of 3.10 and 2 at peak inflammation: median of 3.90) provided a significant difference (P = 0.044). In the second patient, because of the smaller sample size and reduced statistical power (4 with no infection: a median of 1.59 and 2 at peak infection: 3.46), the increase did not reach significance (P = 0.13). In the first case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 1.45 from 2.00 to a peak of 2.89. To compensate for the inhibition of clozapine metabolism, the dose correction factor was 0.69 (1/1.45) or a decrease in dose of approximately one-third. In the second case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 2.56 from 1.15 to a peak of 2.94. Conclusion This provided a dose correction factor of 0.40 (1/2.56) or approximately half the dose, similar to published cases in Caucasians with serious respiratory infections.

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Clozapine Levels After Clozapine Discontinuation

Cited by 17 publications

References 3 publications

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

<p>Self-Report for Measuring and Predicting Medication Adherence: Experts’ Experience in Predicting Adherence in Stable Psychiatric Outpatients and in Pharmacokinetics</p>

Two cases of high serum clozapine concentrations occurring during inflammation in Chinese patients

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