clozapine and Psychoses--Alcoholic

Two hundred and sixteen psychiatric patients (183 men and 33 women) hospitalized in Sct. Hans Hospital were treated with clozapine between 1971-1983. All had been treated previously with one or more neuroleptic(s) and had either failed to respond adequately, or their response was limited by side effects. Eighty-five patients were treated exclusively with clozapine, while the remaining 131 received additional medication, mainly other neuroleptic drugs. The mean clozapine dosage was 317 mg/day (range 50-1200), and the mean duration of treatment was 23/4 years (range 1/12-12). The tolerability to clozapine was determined by an evaluation of haematological changes, pronounced side effects and mortality. One patient treated with clozapine (8 months) and nitrofurantoin (8 days) developed a reversible granulocytopenia. One patient (treated with a combination of drugs) had clinically insignificant depression of the leucocytes and three of segmented granulocytes. Seven had a reduction in thrombocytes. Two patients developed cardiac insufficiency, and four epileptic seizures. None of the patients treated exclusively with clozapine developed neurological side effects. A global estimation of therapeutic effect revealed that clozapine alone or in combination with other neuroleptic drugs was significantly better than previous antipsychotic therapy, although 47-63% of the patients showed no change. It is concluded that clozapine is a potent antipsychotic drug offering particular advantages in the treatment of schizophrenic patients with a pronounced symptomatology and tendency towards developing extrapyramidal side effects. Caution is advised in patients with cardiac insufficiency and epilepsy. There appears to be a slight risk of granulocytopenia, and therefore the present monitoring of WBC should continue in order to prevent this reaction and to obtain more complete information regarding risk of granulocytopenia.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Clozapine; Dementia; Denmark; Dibenzazepines; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Leukocyte Count; Male; Middle Aged; Paranoid Disorders; Psychoses, Alcoholic; Psychoses, Substance-Induced; Psychotic Disorders; Retrospective Studies; Schizophrenia

MHPG concentration in CSF, urinary excretion of NA and A as well as activity of serum DBH were significantly elevated during alcohol delirium as compared to the recovery period. Urinary DA and HVA in CSF did not show any constant change. One single dosage of clozapine (100 mg orally) induces higher urinary NA and A excretion. There is a time course of clozapine action. MHPG in rat brain a single dosage (50 mg/kg) is elevated; after repeated administration (11 days) a decrease is observed. After 10 days of treatment with clozapine (300 mg/day) a decrease of MHPG in CSF can be seen. It is hypothesized that there is a relationship between delirious states and increases central NA turnover.

Topics: Alcohol Withdrawal Delirium; Clozapine; Dibenzazepines; Dopamine; Dose-Response Relationship, Drug; Epinephrine; Humans; Norepinephrine; Psychoses, Alcoholic; Time Factors

Cerebrospinal fluid 5-hydroxyindoleacetic acid and total blood serotonin levels were measured simultaneously in 11 female patients with delirium tremens and nine schizophrenic women with clozapine-induced acute delirium. Both groups had significantly raised levels of 5HIAA in CSF and significantly reduced blood 5HT levels as compared with normal control subjects, symptom-free alcoholics, or clozapine-treated schizophrenics. The two delirious groups were not distinguishable from each other in respect of their CSF 5HIAA or blood 5HT values. After clinical recovery both values returned to normal levels.

Topics: Adult; Alcohol Withdrawal Delirium; Clozapine; Delirium; Dibenzazepines; Female; Humans; Hydroxyindoleacetic Acid; Psychoses, Alcoholic; Schizophrenia; Serotonin