Antipsychotics hematologic effects

The seeds of this transformation were sown some years ago. The first so-called atypical antipsychotic, clozapine (Clozaril), was devised in the 1960s. Clozapine was used widely in Europe until a series of deaths from a toxic hematological (blood) side effect called agranulocytosis occurred in the mid-1970s. Clozapine resurfaced in the 1980s and was approved for use (under strict guidelines) in the United States in 1990. Since that time, several other atypical antipsychotics have been approved, and others loom on the horizon. 

Clozapine has been found effective in patients who did not improve during treatment with first-generation antipsychotics, and since the hematological side effects permit only its restricted use, this dmg has a unique indication for treatment- resistanf schizophrenia. Another unique indication for clozapine is the reduction in the risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorders. The indications of clozapine and its two analogues, olanzapine and quetiapine, are summarized in Tab. 13.5. The US labels of these drugs served as the data source [62-64]. Clozapine and olanzapine, but not quetiapine, are available in intramuscular form, which is helpful in the treatment of acutely agitated patients with diagnoses as defined in Tab. 13.5. 

Tricyclic antidepressants resemble the phenothiazine antipsychotics such as chlorpromazine in structure and function. Like the phenothiazine derivatives (e.g., chlorpromazine), tricyclic antidepressants (e.g., amitriptyline) may reduce the seizure threshold and precipitate seizures in epileptic patients, cause cholestatic jaundice, movement disorders, and hematologic side effects. Unlike the phenothiazine derivatives, the tricyclic antidepressants may increase motor activity, have a very slow onset and long duration of action, a relatively narrow margin of safety, and a strong anticholinergic effect. In fact, dry mouth is the most common side effect, and other anticholinergic effects such as tachycardia, loss of accommodation, constipation, urinary retention, and paralytic ileus have been reported following amitriptyline. 

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