Pharmacometabolomics-guided clozapine therapy in treatment resistant schizophrenia: Preliminary exploration of potential biomarkers

2021 ◽  
pp. 102939
Author(s):  
Sandeep Grover ◽  
Kripa Shanker Kasudhan ◽  
Naveen Murali ◽  
Amol N Patil ◽  
Smita Pattanaik ◽  
...  
Keyword(s):  
Treatment Resistant ◽  
Clozapine Therapy ◽  
Potential Biomarkers

scholarly journals Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated withStreptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Christina Voulgari ◽  
Raphael Giannas ◽  
Georgios Paterakis ◽  
Anna Kanellou ◽  
Nikolaos Anagnostopoulos ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Second Generation ◽  
Causal Relation ◽  
Antipsychotic Agent ◽  
Iliac Vein ◽  
Severe Neutropenia ◽  
Caucasian Woman ◽  
Treatment Resistant ◽  
Clozapine Therapy ◽  
Allergic Vasculitis

Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated byStreptococcus pneumoniaand sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy.

Clozapine: Serious Adverse Side Effects, Drug Interactions, and Other Complications of Therapy

1996 ◽  
Vol 9 (2) ◽  
pp. 118-129 ◽  
Author(s):  
Deanna M. Guith
Keyword(s):  
Side Effects ◽  
Health Care Professionals ◽  
Elderly Population ◽  
Adverse Reactions ◽  
Psychotic Disorders ◽  
Antipsychotic Agent ◽  
The Elderly ◽  
Pharmacological Properties ◽  
Treatment Resistant ◽  
Clozapine Therapy

Clozapine (Clozaril®, Sandoz, East Hanover, NJ), an atypical antipsychotic agent with pharmacological properties considerably different from standard neuroleptics, has been found to be of great benefit especially to patients with treatment-resistant psychotic disorders. However, it is these unique pharmacological properties that have also been associated with mul tiple side effects ranging from the relatively benign (ie, sialorrhea during sleep, dizziness) to the potentially fatal (ie, agranulocytosis, seizures, and respiratory depression) which have limited its use. These untoward side effects are particularly problematic in the elderly population who often have concomitant medi cal illnesses requiring multiple medication regimens, including psychotropics that may interact with cloza pine (ie, benzodiazepines, cimetidine, fluoxetine). Because even the most benign of side effects has the potential of becoming fatal in certain circumstances if left unaddressed, it is imperative for patients, clinicians, pharmacists, and all health care professionals to be aware of adverse reactions and possible complica tions of clozapine therapy to prevent significant morbidity and mortality. Copyright © 1996 by W.B. Saunders Company

Precise pharmacogenetic pharmacometabolomic (PPP) guided clozapine therapy in treatment resistant schizophrenia: Insights from one ethnicity experiment

2021 ◽  
Vol 237 ◽  
pp. 26-28
Author(s):  
Amol N. Patil ◽  
Kripa Shanker Kasudhan ◽  
M. Naveen ◽  
Gurpreet Kaur Batra ◽  
Subho Chakrabarti ◽  
...  
Keyword(s):  
Treatment Resistant ◽  
Clozapine Therapy

scholarly journals Delaying clozapine: how long is too long?

2020 ◽  
Vol 33 (2) ◽  
pp. e100172
Author(s):  
Tom Varghese M ◽  
KS Jyothi ◽  
KS Shaji ◽  
Lekshmi Rita Venugopal
Keyword(s):  
Correlation Coefficient ◽  
Symptom Score ◽  
Negative Symptom ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Duration Of Treatment ◽  
Clozapine Therapy ◽  
Syndrome Scale ◽  
The Mean ◽  
Negative Syndrome

BackgroundAlthough clozapine is the most effective drug for treatment-resistant schizophrenia, its use remains restricted in clinical practice in India. The delay in initiating treatment with clozapine and its impact on disease outcome needs evaluation.AimTo identify the implications of delaying clozapine initiation in clinical outcomes among people with treatment-resistant schizophrenia.MethodsSubjects with treatment-resistant schizophrenia, stabilised on clozapine monotherapy, were recruited from the outpatient clinic of a general hospital psychiatry unit offering tertiary care services in Thrissur district, Kerala, India. A retrospective cohort design was employed, and information on duration of illness, total duration of treatment and duration of treatment with clozapine was collected. Present symptom status was measured using the Positive and Negative Syndrome Scale. Factors associated with higher symptom scores were analysed using an independent sample t test, Spearman correlation and multiple linear regression.ResultsForty subjects stabilised on long-term clozapine therapy formed the study sample. The mean dose of clozapine used in the study population was 200 mg. The mean duration of antipsychotic treatment before starting clozapine was 89.3 months (7.4 years). The duration of treatment before starting clozapine was found to have a significant positive association with the total Positive and Negative Syndrome Scale score (correlation coefficient 0.40; p=0.01) and negative symptom score (correlation coefficient 0.33; p=0.04). The multiple regression analysis adjusting for covariates showed that the duration of treatment before starting clozapine was an independent factor associated with a higher negative symptom score in the Positive and Negative Syndrome Scale (slope β=0.05; p=0.02; R2=0.27).ConclusionPoor treatment outcomes in treatment-resistant schizophrenia could be secondary to a delay in initiating clozapine therapy.

Influence of clozapine to modified electroconvulsive therapy in the treatment resistant schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. s817-s817
Author(s):  
Y. Kikuchi ◽  
T. Kanbayashi ◽  
T. Shimizu
Keyword(s):  
Electroconvulsive Therapy ◽  
Treatment Resistant ◽  
First Line ◽  
Clozapine Therapy ◽  
Significant Difference ◽  
Augmentation Strategy ◽  
Competing Interest ◽  
Modified Electroconvulsive Therapy ◽  
Monitoring Service ◽  
Effective Drugs

IntroductionClozapine is one of the most effective drugs for the treatment resistant schizophrenia (TRS). It was reported that modified electroconvulsive therapy (mECT) may be an effective clozapine augmentation strategy in TRS.ObjectiveThe objective of this study was to investigate the influence of clozapine to mECT in the TRS.MethodsForty-seven patients were recruited in this study, but eight patients were excluded because clozapine was discontinued by reason of side effects. Ultimately, 39 patients were enrolled.ResultsSeventeen patients received mECT before clozapine therapy. Two patients continued mECT after starting clozapine therapy. There was a significant difference between before–after clozapine therapy (χ2 test, P< 0.01). Intermittent mECT was performed for 3 patients before clozapine and for one patient after starting clozapine.DiscussionThis result suggests that clozapine therapy reduces mECT. In Japan, the first-line treatment for TRS is CLO. mECT is recommended for clozapine resistant schizophrenia patients. Prescription of CLO is limited in the part of medical facility because all physicians who prescribe clozapine must be registered with the clozaril patient monitoring service in Japan. It is considered that mECT is more readily selected than clozapine therapy. Therefore, the number of mECT is not reduced generally.ConclusionClozapine therapy reduces the necessity of mECT.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clozapine underutilization in treatment-resistant schizophrenia

2015 ◽  
Vol 5 (2) ◽  
pp. 63-67
Author(s):  
Robert J. Stanton ◽  
Chris Paxos ◽  
Werner J. Geldenhuys ◽  
B Pharm ◽  
Jessica L. Boss ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Second Generation ◽  
Treatment Resistant ◽  
Antipsychotic Therapy ◽  
Clozapine Therapy ◽  
First Line Therapy ◽  
Therapeutic Benefits ◽  
Second Generation Antipsychotics ◽  
Life Threatening ◽  
Positive And Negative Symptoms

Abstract It has been shown that up to one third of patients with schizophrenia do not respond to antipsychotic therapy. Thus, treatment-resistant schizophrenia (TRS) remains a major mental health care challenge. Clozapine has been shown to provide superior therapeutic benefits and is approved as first-line therapy for TRS. These benefits include improvement in both positive and negative symptoms, and reduction of suicidal behavior in patients with schizophrenia. Clozapine, however, remains significantly underused for TRS. A major reason for clozapine's underuse is its substantial adverse effect profile, mainly the risk of life-threatening agranulocytosis which necessitates regular hematologic monitoring. Another factor contributing to reduced clozapine prescribing is the increased use of other second-generation antipsychotics. In TRS patients, there is often a considerable delay in clozapine use, which is prescribed only after other unsuccessful second-generation antipsychotic trials. To combat this trend, there is a push for increased awareness to optimize clozapine prescribing. An important aspect in improving the use of clozapine therapy is physician and patient education. Furthermore, pharmacist involvement can improve clozapine prescription trends in TRS.

scholarly journals Routine clozapine assay monitoring to improve the management of treatment-resistant schizophrenia

2021 ◽  
pp. 1-4
Author(s):  
David Kitchen ◽  
Alex Till ◽  
Panchu Xavier
Keyword(s):  
High Risk ◽  
Clinical Utility ◽  
Target Range ◽  
Therapeutic Drug ◽  
Treatment Resistant ◽  
Clozapine Therapy ◽  
Routine Monitoring ◽  
Number Of Patients ◽  
Routine Therapeutic Drug Monitoring ◽  
Health Trust

Aims and method Routine therapeutic drug monitoring in clozapine therapy has previously not been considered justifiable. Using observational data, the clinical utility of annual clozapine assay monitoring is explored within a large mental health trust. Results After the introduction of routine monitoring, the rate of clozapine assays rose to 2.3 per patient per year, with a consistent reduction in high-risk clozapine assays (<0.1 mg/L or >1.0 mg/L or any result more than 24 months old). High-risk assays are associated with a mortality rate of 31.6 deaths per 1000 patients, more than twice that of those within the target range (0.35–0.60 mg/L and conducted within the past 12 months) (P = 0.048). Clinical implications Routine clozapine assay monitoring has significant clinical utility. Our simple but targeted approach can be readily implemented to reduce the number of patients with high-risk clozapine assay levels, potentially reduce all-cause mortality and provide optimal treatment for those with treatment-resistant schizophrenia.

scholarly journals A Legal Right to Clozapine Therapy for Incarcerated Individuals With Treatment-Resistant Schizophrenia

2021 ◽  
pp. appi.ps.2020008
Author(s):  
Theodore R. Zarzar ◽  
Joseph B. Williams ◽  
Megan E. Pruette ◽  
Brian B. Sheitman
Keyword(s):  
Treatment Resistant ◽  
Clozapine Therapy ◽  
Legal Right
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