Agranulocytosis in patients treated with clozapine

Amsler, H. A.; Teerenhovi, Lasse; Barth, Earl E.; Harjula, K.; Vuopio, P

doi:10.1111/j.1600-0447.1977.tb00224.x

Cited by 142 publications

(35 citation statements)

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“…The clinical features of clozapine-induced agranulocytosis were described in publications from Finland in the mid-1970s, where a selectively high incidence was found. In Finland a cluster of 7.09 cases appeared per 1000 patients treated, compared with 0.1 to 0.2 per 1000 in other European countries (Amsler et al 1977;Anderman & Griffith 1977;de la Chapelle et al 1977;IdanpaanHeikkila et al 1977;Senn et al 1977).…”

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confidence: 95%

“…Agranulocytosis is a distressing and potentially fatal complication of therapy with clozapine (Amsler et al 1977;Anderman & Griffith 1977;Chapelle et al 1977;Idiinpaan-Heikkilii et al 1977;Lieberman et al 1988;Senn et al 1977). Despite its efficacy in controlling clinical manifestations of serious mental disease and its freedom from extrapyramidal side effects, I to 2% of clozapine-treated patients may develop a precipitous loss of polymorphonuclear neutrophils (PMNs).…”

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confidence: 97%

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On the Possible Mechanisms and Predictability of Clozapine†-Induced Agranulocytosis

et al. 1992

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Studies were conducted on serum removed from 15 patients before, during, and after, clozapine-induced agranulocytosis. Cytotoxic studies were compared with samples taken from patients during treatment with clozapine who did not develop agranulocytosis or treatment controls (TC); additional controls consisted of allogeneic (NC) and autogeneic serum from apparently normal people. The effect of serum on measurable functions of polymorphonuclear neutrophils (PMNs) taken from normal people was tested. Procedures under study included suppression of postphagocytosis-induced 14C02-indicated respiratory burst, as well as ejection of try pan blue by test PMNs. PMNs exposed to active agranulocytosis serum plus complement displayed diminished 14C02 emission during phagocytosis or failed to eject trypan blue. PMNs exposed to serum of TC and NC continued to function normally as regards 14C02 emission and trypan blue ejection. Five patients studied before the development of agranulocytosis showed suppressed PMN function, which increased to peak value during agranulocytosis and then disappeared within 40 days of recovery. Similar suppression of colony forming units of granulocytes and macrophages (CFU-GM) was found whenever agranulocytosis serum was included in the marrow culture. The cytotoxic material required complement for its full expression, was not dialysable, was neutralised by anti-IgM serum, and was absorbed by test PMNs. Furthermore, solutions of clozapine or 5 of its metabolites offered no similar suppression of PMN function in vitro after incubation in an aqueous medium or with normal serum. These observations favour development of an immunogenic clone in sensitive people during active treatment with clozapine, which eventually leads to precipitous depletion of PMNs and their precursors. The early appearance of this suppressive substance may offer an early warning for development of agranulocytosis.

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confidence: 95%

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On the Possible Mechanisms and Predictability of Clozapine†-Induced Agranulocytosis

et al. 1992

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“…It may be related to the modulating of neurotransmitter balance in the central nervous system (CNS) by CLO [3]. CLO, however, also affects the immune system [4][5][6] and one serious adverse effect of CLO treatment is agranulocytosis [7,8]. The abnormalities in the immune system of patients suffering from schizophrenia have been described by Smith [9], Maes et al [6] and Ganguli et al [10].…”

Section: Introductionmentioning

confidence: 99%

Decreased Production of Reactive Oxygen Species by Blood Monocytes Caused by Clozapine Correlates with EEG Slowing in Schizophrenic Patients

Gross

Joffe

Joutsiniemi³

et al. 2003

Neuropsychobiology

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We have earlier reported an increased theta-power value in clozapine (CLO)-treated patients with schizophrenia, nonresponsive to conventional antipsychotics. We also found that the decrease in the production of reactive oxygen species (ROS), induced by CLO, by peripheral blood monocytes (MO) of these patients correlates with clinical improvement. MO share the capability of ROS production with their more mature descendants, microglia of the brain. We hypothesized that the CLO-related changes in peripheral blood MO might be related to a parallel process in microglia and thus be reflected in brain activity. In those 8 patients for whom both QEEG and MO data were available, we explored possible relationships between these parameters. A clear-cut correlation between ROS production (R² = 0.929, p < 0.05) for nonstimulated MO, and (R² = 0.907, p < 0.001) for stimulated MO and theta-power values in the central frontal electrode (F_z) was found. It is intriguing to speculate that the EEG slowing is a result of the modulatory action of the activated microglial cells in the central nervous system via production of ROS or cytokines or both. However, this proposition has to be confirmed by future research.

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“…The report of 16 cases of agranulocytosis (8 with fatal outcome) among 2.500 to 3.200 clozapine recipients in Finland in 1975 (Amsler et al, 1977;Idfinpfifin-Heikkilfi et al, 1977) led to a restricted use of clozapine from that time onwards, the main indication being schizophrenia, which is refractory to standard therapy and to the compulsory requirement of weekly haematological monitoring during the first 18 weeks of clozapine treatment. The weekly blood counts showed no pathological results in any of our patients in agreement with the other studies.…”

Section: Discussionmentioning

confidence: 96%

Therapeutic effect of clozapine in psychotic decompensation in idiopathic Parkinson's disease

Pinter

Helscher

1993

J Neural Transm Gen Sect

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Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25-125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months. Our results support the assumption that clozapine has a potent antipsychotic effect in the treatment of psychotic decompensation in advanced Parkinson's disease in carefully selected patients. We saw no negative influence of the neuroleptic on extrapyramidal symptoms.

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Agranulocytosis in patients treated with clozapine

Cited by 142 publications

References 4 publications

On the Possible Mechanisms and Predictability of Clozapine†-Induced Agranulocytosis

On the Possible Mechanisms and Predictability of Clozapine†-Induced Agranulocytosis

Decreased Production of Reactive Oxygen Species by Blood Monocytes Caused by Clozapine Correlates with EEG Slowing in Schizophrenic Patients

Therapeutic effect of clozapine in psychotic decompensation in idiopathic Parkinson's disease

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