scholarly journals Using clozapine in clinical practice

2011 ◽  
Vol 17 (4) ◽  
pp. 256-265 ◽  
Author(s):  
Ann M. Mortimer
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Antipsychotic Drugs ◽  
Clinical Excellence ◽  
Treatment Resistant ◽  
Clozapine Treatment ◽  
Optimal Outcomes ◽  
Initial Effort ◽  
Poor Tolerability ◽  
Realistic Appraisal

SummaryClozapine remains underutilised as the only antipsychotic for treatment-resistant schizophrenia, despite liberal National Institute for Health and Clinical Excellence guidelines for its consideration. Bearing in mind its monitoring requirements and poor tolerability, suggestions are made for patients who fail to improve on other antipsychotic drugs. Clozapine may be offered to apparently unsuitable patients, although this is fraught with difficulty. A realistic appraisal of the alternatives is essential in this situation. Optimising plasma clozapine levels, alongside the use of rehabilitative interventions and adjuncts as necessary, will maximise efficacy, and there are numerous options to minimise side-effects. Clozapine requires a lengthier trial than other antipsychotics and discontinuation should be avoided if possible, as the results are generally very poor. Established successful clozapine treatment can induce substantial functional gains which accrue with time: patients are retained in treatment and relapse is prevented. Such optimal outcomes justify the initial effort expended by all.

Delirium on clozapine: A tale of friend turned foe-A case report

2020 ◽  
pp. 009121742097282 ◽  
Author(s):  
Aparna Das ◽  
Rebecca Minner ◽  
Lewis Krain ◽  
John Spollen
Keyword(s):  
Case Report ◽  
Clinical Practice ◽  
Side Effects ◽  
Adverse Effects ◽  
Older Adult ◽  
Psychiatric Illness ◽  
Management Strategies ◽  
Treatment Resistant ◽  
Drug Of Choice ◽  
Life Threatening

Treatment resistant schizophrenia (TRS) is often encountered in clinical practice. Clozapine remains the drug of choice in the management of TRS. Several studies have shown that clozapine is the most effective antipsychotic medication to date for TRS. But it is also well known that it has multiple side effects. Some side effects are transient and relatively benign, while other adverse effects are menacing, serious and life-threatening. Delirium may occur with clozapine and is a therapeutic challenge as there is always a risk of precipitating delirium on clozapine rechallenge. Limited management strategies are available as alternatives for the management of psychiatric illness stabilized on clozapine. In this case report, we describe an older adult patient who developed delirium on clozapine. The aims of this case report are to discuss the mechanism by which clozapine leads to delirium, revisit various factors which could possibly lead to delirium, and discuss the different management strategies available for management of psychiatric illness for a patient previously stabilized on clozapine.

Treatment of Acute Mania

CNS Spectrums ◽  
2003 ◽  
Vol 8 (12) ◽  
pp. 917-928 ◽  
Author(s):  
Paul E. Holtzheimer ◽  
John F. Neumaier
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Drug Administration ◽  
Mood Stabilizers ◽  
Acute Mania ◽  
Treatment Resistant ◽  
Short Term ◽  
The Past ◽  
Term Tolerability

AbstractMood stabilizers have evolved considerably over the past decade. Lithium, divalproex, and olanzapine are currently Food and Drug Administration-approved for the treatment of acute mania. A number of new and traditional medications have also been tested and are commonly used in clinical practice. Several strategies for managing treatment-resistant mania have been suggested, but few have been rigorously tested. Emphases on rapid stabilization and fewer side effects have raised the bar for what is expected from mood stabilizers and the successful treatment of mania involves a delicate balance between swiftness, short-term tolerability, and long-term safety.

Combination of amisulpride and olanzapine in treatment-resistant schizophrenic psychoses

2004 ◽  
Vol 19 (1) ◽  
pp. 56-58 ◽  
Author(s):  
Mathias Zink ◽  
Fritz A. Henn ◽  
Johannes Thome
Keyword(s):  
Side Effects ◽  
Antipsychotic Drugs ◽  
Therapeutic Option ◽  
Treatment Resistant ◽  
Combined Application ◽  
Drug Doses

AbstractTreatment-resistant schizophrenia often leads to combined application of antipsychotic drugs. We report first experience with the combination of olanzapine and amisulpride. Improvement of psychopathological state and side effects could be achieved, and drug doses were lower than under monotherapy. We thus conclude that this approach represents a useful therapeutic option.

The assessment and management of treatment-resistant schizophrenia in perspective

1995 ◽  
Vol 10 (S1) ◽  
pp. 3s-5s ◽  
Author(s):  
HY Meltzer ◽  
H Hippius
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotic ◽  
Antipsychotic Drugs ◽  
Subjective Evaluation ◽  
Treatment Resistance ◽  
Antipsychotic Agents ◽  
Therapeutic Effects ◽  
Extrapyramidal Side Effects ◽  
Clozapine Treatment ◽  
Results Of Treatment

SummaryConsensus was reached on the five following points: (1) “Treatment resistance” is a term which is widely used, but not adequately defined. In particular, definitions of “responders” and “non-responders” need to be more precise. (2) There is a need to extend the assessment of the results of treatment to include factors such as quality of life and the subjective evaluation by the patient and relatives. (3) Clozapine (Clozaril®/Leponex®) has become the standard for atypical antipsychotic drugs. The adjective “atypical” is not an exact descriptor. The vague nature of the term leads to confusion with other drugs that are putative atypical antipsychotic agents but have different properties. D2 dopamine receptor antagonism is the single factor common to all antipsychotic drugs. Antagonism at a specific D2-like receptor may underlie the atypical antipsychotic actions of clozapine. Drugs described as being atypical antipsychotics share a relatively low incidence of extrapyramidal side effects. (4) Clozapine is the only drug that produces antipsychotic (therapeutic) effects at doses that do not result, in significant extrapyramidal side effects. This may be due to the fact that antipsychotic efficacy is obtained with clozapine in doses that result in significantly less striatal D2 occupancy. Other factors including concomitant 5-HT2 antagonism, may contribute to the lack of motor side effects observed with clozapine treatment. (5) Clozapine is the only drug currently well proven in therapy-resistant schizophrenia, and there is a case for its earlier use in patients who can be anticipated to become therapy resistant. Other antipsychotic therapies remain unproven in this group of patients.

scholarly journals A study of clozapine and long-term hospitalisation rates

2004 ◽  
Vol 28 (8) ◽  
pp. 285-288 ◽  
Author(s):  
Alan A. Woodall ◽  
David B. Menkes ◽  
Thomas R. Trevelyan ◽  
Colin P. Lanceley
Keyword(s):  
Side Effects ◽  
Older Patients ◽  
Clinical Excellence ◽  
Clinical Implications ◽  
Treatment Resistant ◽  
Nice Guidelines ◽  
Resistant Disease ◽  
Factors Influencing ◽  
The Mean

Aims and MethodThe aim of the study was to investigate the use of clozapine in treatment-resistant schizophrenia and its impact on hospitalisation rates when prescribed in accordance with National Institute for Clinical Excellence (NICE) guidelines. Case records were examined of patients admitted to the psychiatric unit of Glan Clwyd Hospital between 1996 and 2001.ResultsOf 59 patients identified as having treatment-resistant schizophrenia, 83% had been considered for clozapine, 48% were taking clozapine, 20% had refused the drug and 15% had stopped taking it because of side-effects. The mean annual hospitalisation rate for patients receiving clozapine for a minimum of 3 years was 13.5 days, markedly lower than those not receiving this drug (34.0 days, P=0.03). Older patients were less likely to have been offered clozapine (P=0.006).Clinical ImplicationsThis study supports the NICE guidelines recommending clozapine for patients with treatment-resistant disease. Clozapine is offered less often to older patients; factors influencing this require investigation.

Pharmacological management of treatment-resistant schizophrenia: fundamentals of clozapine

2018 ◽  
Author(s):  
Yvonne Yang ◽  
Stephen Marder
Keyword(s):  
Clinical Trials ◽  
Weight Gain ◽  
Side Effects ◽  
Plasma Concentrations ◽  
Psychotic Symptoms ◽  
Controlled Clinical Trials ◽  
Treatment Resistant ◽  
Minimum Duration ◽  
Pharmacological Management ◽  
Clozapine Treatment

Evidence from controlled clinical trials supports the prescribing of clozapine for patients with treatment-resistant schizophrenia (TRS). Early studies focused on severely ill TRS patients. More recent studies indicate that clozapine can be effective for patients who are relatively stable but are burdened by persistent psychotic symptoms. Clozapine treatment is associated with a substantial side effect burden, including sedation, orthostasis, weight gain, constipation, and seizures. In addition, because of a risk of potentially fatal agranulocytosis, clozapine patients require regular monitoring of their neutrophil count. Measuring clozapine plasma concentrations can be helpful in managing patients with severe side effects and those with an inadequate clinical response. A trial of clozapine should consist of a minimum duration of 12 weeks.

Predictors of discontinuation on clozapine: a population study

2003 ◽  
Vol 20 (4) ◽  
pp. 115-118 ◽  
Author(s):  
Steve MacGillivray ◽  
Steve J Cooper ◽  
Barbara English ◽  
Helen Millar ◽  
Brian Williams
Keyword(s):  
Side Effects ◽  
Demographic Data ◽  
Treatment Resistance ◽  
Clinical Excellence ◽  
Treatment Resistant ◽  
Kaplan Meier ◽  
Number Of Factors ◽  
Co Morbidity ◽  
Before And After ◽  
Monitoring Service

AbstractObjectives: A quarter of people with schizophrenia may be classed as ‘treatment-resistant’. Clozapine is an antipsychotic that holds significant potential benefit for this patient group and has recently been recommended by the National Institute for Clinical Excellence. Early discontinuation is common. This study explores the factors that predict such discontinuation.Method: This retrospective cohort design was carried out on two hundred and one people with treatment resistant schizophrenia who had commenced clozapine between 1990 and 1997 identified from the Clozaril Patient Monitoring Service (CPMS) in Northern Ireland. Clinical and socio-demographic data was collected for three years before and after commencement on clozapine. Kaplan Meier survival analyses were conducted to identify differences in discontinuation rates according to a range of variables.Results: Forty-five per cent of patients had discontinued before three years. No difference in rates were found between men and women, nor whether side-effects were reported or not Patients who had commenced clozapine at an older age had significantly higher cessation rates. People who had started clozapine at age 50+ were four times more likely to stop taking clozapine within three years than people aged between 17-29 years.Conclusions: Differences in continuation rates may be due to a number of factors. Treatment resistance may increase with age, side-effects may worsen or patient willingness to tolerate such effects may reduce. Alternatively, clinicians may be more anxious about prescribing clozapine as levels of co-morbidity increase. Further research is required to identify precise reasons and develop interventions to reduce discontinuation rates among older patients.

Haematologic malignancies associated with clozapine v. all other antipsychotic agents: a pharmacovigilance study in VigiBase®

2020 ◽  
pp. 1-8 ◽  
Author(s):  
Basile Chrétien ◽  
Véronique Lelong-Boulouard ◽  
Sylvain Chantepie ◽  
Marion Sassier ◽  
Mickael Bertho ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Antipsychotic Drugs ◽  
Antipsychotic Agents ◽  
Reporting Odds Ratio ◽  
Treatment Resistant ◽  
Clozapine Treatment ◽  
Pharmacovigilance Database ◽  
Time To Onset ◽  
Dose Dependent ◽  
Haematologic Malignancies

Abstract Background Clozapine is mainly used in patients with treatment-resistant schizophrenia and may lead to potentially severe haematologic adverse events, such as agranulocytosis. Whether clozapine might be associated with haematologic malignancies is unknown. We aimed to assess the association between haematologic malignancies and clozapine using Vigibase®, the WHO pharmacovigilance database. Methods We performed a disproportionality analysis to compute reporting odds-ratio adjusted for age, sex and concurrent reporting of antineoplastic/immunomodulating agents (aROR) for clozapine and structurally related drugs (loxapine, olanzapine and quetiapine) compared with other antipsychotic drugs. Cases were malignant lymphoma and leukaemia reports. Non-cases were all other reports including at least one antipsychotic report. Results Of the 140 226 clozapine-associated reports, 493 were malignant lymphoma cases, and 275 were leukaemia cases. Clozapine was significantly associated with malignant lymphoma (aROR 9.14, 95% CI 7.75–10.77) and leukaemia (aROR 3.54, 95% CI 2.97–4.22). Patients suffering from those haematologic malignancies were significantly younger in the clozapine treatment group than patients treated with other medicines (p < 0.001). The median time to onset (available for 212 cases) was 5.1 years (IQR 2.2–9.9) for malignant lymphoma and 2.5 years (IQR 0.6–7.4) for leukaemia. The aROR by quartile of dose of clozapine in patients with haematologic malignancies suggested a dose-dependent association. Conclusions Clozapine was significantly associated with a pharmacovigilance signal of haematologic malignancies. The risk-benefit balance of clozapine should be carefully assessed in patients with risk factors of haematologic malignancies. Clozapine should be used at the lowest effective posology.

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