clozapine and Anemia--Aplastic

Haematological abnormalities are frequently encountered during treatment with antipsychotic drugs. Most of these are mild and of no clinical significance. In the case of many, there is often difficulty in establishing a cause-and-effect relationship between the drug and the abnormality. However, in a small minority of patients, hazardous, potentially life-threatening haematological effects can occur due to a combination of pharmacological and host factors. These include leucopenia and agranulocytosis. Although such effects are rare, it is essential that they are diagnosed and managed promptly. In this paper, the authors review the haematological adverse effects and safety of antipsychotic drugs and present a strategy for prevention.

Topics: Agranulocytosis; Anemia, Aplastic; Antipsychotic Agents; Clozapine; Hematologic Diseases; Humans; Leukopenia

The development of antipsychotic drugs has followed two complementary approaches, either towards highly specific actions (e.g. on the dopamine receptor) or targeting a broad range of receptors. The properties of 'atypical' agents challenge the original dopamine hypothesis and suggest roles for a variety of dopamine receptors and for other pathways, such as serotonin. Older drugs, despite their proven efficacy in relieving many schizophrenic symptoms, have several drawbacks, being ineffective in some patients, relatively ineffective against negative symptoms, and causing adverse neurological effects which may, in turn, be associated with poor compliance. Among newer agents, currently available ones, such as clozapine and risperidone, offer the possibility of more effective control of negative symptoms and an improved side-effect profile, while others are in earlier stages of development. However, much still remains to be understood about their mechanisms of action.

Topics: Agranulocytosis; Anemia, Aplastic; Antipsychotic Agents; Brain; Clozapine; Humans; Neurologic Examination; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Drug-induced agranulocytosis is a highly individualized and unexpected reaction to specific drugs. It may be due to immunogenic or cytotoxic factors. Most instances are produced by a poorly understood immune response to immunogenic drugs. Others are associated with direct suppression of marrow committed stem cells by the direct action of the offending drug or its toxic metabolic end products. The early appearance of polymorphonuclear neutrophil (PMN) antibodies may offer an early warning to sensitized patients. Antibodies, if present, disappear shortly after the drug is discontinued. Agranulocytosis, due to direct action of the drug, is characterized by morphologic aplasia of marrow and is more likely to occur if the affected host has a concomitant defect in marrow cellular proliferation. Accumulation of toxic metabolic end products such as arene oxides may occur if the host is deficient in a microsomal system required to dispose of this material.

Topics: Agranulocytosis; Aminopyrine; Anemia, Aplastic; Bone Marrow; Clozapine; Female; Hematopoiesis; Hematopoietic Stem Cells; Humans; Male; Neutrophils; Phenothiazines

Topics: Anemia, Aplastic; Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders

Topics: Agranulocytosis; Anemia, Aplastic; Antipsychotic Agents; Clozapine; Drug Monitoring; Humans; Isoxazoles; Neutropenia; Piperidines; Remoxipride; Risperidone; Schizophrenia