Clozapine and Agranulocytosis

Griffith, Rosemary; Saameli, K

doi:10.1016/s0140-6736(75)90135-x

Cited by 73 publications

(33 citation statements)

References 5 publications

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“…In addition, early observations indicated the potential of clozapine to have some therapeutic benefit among patients who had failed to respond to other agents. At the same time, a series of cases of agranulocytosis associated with clozapine were reported in Finland and elsewhere (40). This led to a delay in the further development of clozapine in the U.S.…”

Section: Treatment Refractory Illness and Clozapinementioning

confidence: 99%

Past and Present Progress in the Pharmacologic Treatment of Schizophrenia

Kane

Correll²

2010

J. Clin. Psychiatry

208

185

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Section: Treatment Refractory Illness and Clozapinementioning

confidence: 99%

Past and Present Progress in the Pharmacologic Treatment of Schizophrenia

Kane

Correll²

2010

J. Clin. Psychiatry

208

185

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“…Despite its clinical utility among some treatment-resistant patients, clozapine is associated with potentially serious hematologic consequences, including agranulocytosis (97,139). In the clinical trial experience, no statistically significant differences were found between the olanzapine and placebo groups in the proportions of patients with high or low categorical hematology values (data on file).…”

Section: Hematologymentioning

confidence: 93%

“…These findings suggested that serotonin is likely to play an important role in the pathophysiology of schizophrenia and catalyzed the development of a second generation of so-called "atypical" antipsychotic agents. However, the use of clozapine has been limited to severely ill, treatment-resistant patients because of its associated risk of agranulocytosis (97,139). Hence, recent research efforts have focused on at least matching some of the benefits of clozapine in the context of a wider safety margin.…”

Section: Introductionmentioning

confidence: 99%

Olanzapine: Preclinical and Clinical Profiles of a Novel Antipsychotic Agent

Tollefson

Taylor

2000

CNS Drug Reviews

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The novel antipsychotic agent olanzapine (Zyprexa ® , Eli Lilly and Company) is a thienobenzodiazepine analog marketed for the treatment of schizophrenia. Olanzapine's diverse receptor binding profile and greater affinity for serotonin receptors over dopamine receptors is thought to impart antipsychotic efficacy with a low incidence of serious extrapyramidal symptoms (EPS). With once daily dosing steady-state plasma concentrations reached within approximately 1 week. Olanzapine is extensively metabolized by the liver, is mostly excreted in the urine, and has few drug intractions. In clinical trials, the efficacy of olanzapine for treating schizophrenia is better than placebo and haloperidol and comparable to risperidone. Olanzapine may also ameliorate some comorbid symptoms including negative symptoms, depression, anxiety, substance abuse, and cognitive dysfunction, and it is effective in the long-term maintenance of response, treatment-resistance, and improving quality of life. The overall direct costs are lower with olanzapine treatment compared with haloperidol or risperidone treatment. In clinical trials, olanzapine demonstrates a favorable safety profile. The most frequently reported treatment-emergent adverse events are somnolence, schizophrenic reaction, insomnia, headache, agitation, rhinitis, and weight gain. Significantly fewer EPS (based on formal rating scales) and incidences of tardive dyskinesia have been reported for olanzapine compared with haloperidol. Olanzapine has not been associated with persistent elevations of prolactin above the upper limit of normal nor has it been associated with clinically significant changes in cardiac QT c interval. Fewer incidences of suicide attempts have been reported with olanzapine compared with placebo, haloperidol, or risperidone treatments. There is evidence that olanzapine may be effective in the treatment of mood disorders, psychosis associated with 303

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“…Described initially as " tricyclic antidepressant with a neuroleptic properties " (2) , this agent has challenged the present " neuroleptic dogma " that every antipsychotic agent should have extrapyramidal adverse events as an essential feature necessary to illicit antipsychotic response. In the 1970s, the advantages of its use in severely ill schizophrenics and in others who did not respond to conventional antipsychotics were outweighed by the dangers when 13 patients in Finland developed agranulocytosis and eight of them died during their treatment (3) . Over the years it has come to light that agranulocytosis is a reversible process, and that the clozapine can be discontinued before the development of infection and be safely readministered at a later time (4) .…”

Section: Introductionmentioning

confidence: 99%

The use of clozapine for the treatment of schizophrenia and implications for suicide prevention

Novakovic¹,

Sher²

2012

International Journal on Disability and Human Development

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Considerable progress has been made in the treatment of schizophrenia and other psychotic disorders ever since the discovery of chlorpromazine in the early 1950s and the subsequent discovery of the group of tricyclic chemical compounds including clozapine. On the spectrum of the contemporary pharmacological treatments for schizophrenia, atypical antipsychotic agents render a signifi cant portion. Clozapine continues to play a pivotal role in the treatment of psychotic disorders, despite the emergence of new antipsychotic agents on the market. Among patients with schizophrenia, suicide is the main cause of death. Factors associated with suicide in patients with schizophrenia include previous suicide attempts, inadequate antipsychotic medication, noncompliance, substance abuse and non-response to antipsychotic medication. Clozapine reduces suicidal behavior in patients with schizophrenia. Clozapine has been shown to have a substantial effect on attempted suicide and completed suicide. The mode of action of clozapine in preventing suicide is not known. The various hypotheses proposed include its effects on neurotransmitters, on serum lipid levels, its antidepressant effects or the increased contact with healthcare workers during visits for blood monitoring.

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Clozapine and Agranulocytosis

Cited by 73 publications

References 5 publications

Past and Present Progress in the Pharmacologic Treatment of Schizophrenia

Past and Present Progress in the Pharmacologic Treatment of Schizophrenia

Olanzapine: Preclinical and Clinical Profiles of a Novel Antipsychotic Agent

The use of clozapine for the treatment of schizophrenia and implications for suicide prevention

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