Weight gain, metabolic parameters, and the impact of race in aggressive inpatients randomized to double-blind clozapine, olanzapine or haloperidol.
OBJECTIVE
The second-generation antipsychotic agents clozapine and olanzapine have been associated with weight gain and increased lipid and glucose blood levels. Since some of the neurotransmitters that are impaired in aggressive patients are involved in lipid/glucose metabolism, aggressive patients may represent a subgroup with a differential profile of adverse metabolic reactions to these medications. The goal of this study was to assess the effects of clozapine and olanzapine in comparison to the first-generation agent haloperidol on these metabolic parameters in aggressive patients with schizophrenia.


METHODS
110 inpatients with schizophrenia and a history of physical assaults were included in a randomized double-blind 12-week study. Fasting glucose, cholesterol and triglycerides were collected at baseline and at the end of the study. Ninety-three patients provided blood samples at baseline and at least at one point after randomization to clozapine (N=34), olanzapine (N=31) or haloperidol (N=28).


RESULTS
There were significant differences among the three medication groups in weight gain and in increases in blood lipids and glucose. Patients on haloperidol showed no increase on any of these parameters. Patients on olanzapine gained the most weight, but patients on clozapine had the greatest increases in cholesterol, triglyceride, and glucose. An effect of ethnicity was observed, as African-American patients were more likely to develop metabolic abnormalities than other ethnic groups, especially on clozapine.


CONCLUSIONS
In this prospective randomized trial, clozapine and olanzapine were associated with weight gain. Clozapine was associated with increases in both lipids and glucose. This effect was most prominent in the African-American patients.
Krakowski
Menahem
M
Nathan Kline Institute for Psychiatric Research, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States. Krakow@nki.rfmh.org
Czobor
Pal
P
Citrome
Leslie
L
D000328:Adult; D000374:Aggression / Q000187:drug effects*; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003024:Clozapine / Q000627:therapeutic use; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D007297:Inpatients; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011446:Prospective Studies; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
D014150:Antipsychotic Agents; D001786:Blood Glucose; D001569:Benzodiazepines; D002784:Cholesterol; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine