Patterns of concomitant psychotropic medication use during a 2-year study comparing clozapine and olanzapine for the prevention of suicidal behavior.
BACKGROUND
Results from the International Suicide Prevention Trial (InterSePT) indicate that clozapine is more effective than olanzapine in reducing suicidal behavior in schizophrenic and schizoaffective patients. However, because InterSePT allowed the uncontrolled use of concomitant psychotropic medications (CPMs), it is possible that the antisuicidal effect of clozapine may have been influenced by greater use of such agents. This article describes the use patterns of CPMs during InterSePT and examines whether CPM use may have affected study outcome.


METHODS
In this study, 479 patients received clozapine and 477 patients received olanzapine. Concomitant psychotropic medications were grouped into 4 classes: antipsychotics, antidepressants, sedatives/anxiolytics, and mood stabilizers. The doses of each CPM were converted into dosage equivalents of standard reference drugs. An analysis of covariance was performed to compare mean daily doses of CPMs between the 2 groups over the 2-year treatment period. The duration of treatment for each patient was 2 years, with the first patient entering the study in March 1998 and the last patient completing treatment in February 2001.


RESULTS
Approximately 90% of patients in both treatment groups received at least 1 CPM. The mean +/- SD number of CPMs per patient was 3.8 +/- 2.90 in the clozapine group and 4.2 +/- 3.16 in the olanzapine group. For each CPM class, the mean daily dose was statistically significantly lower in the clozapine group (antipsychotics, p <.001; antidepressants, p <.01; sedatives/anxiolytics, p <.001; mood stabilizers, p <.05). Analyses of CPM use by study intervals, suicide attempters versus nonattempters, study completers versus noncompleters, and geographic region resulted in similar findings.


CONCLUSIONS
The results support the conclusion that the effects of clozapine in reducing the risk of suicidal behavior derive from its intrinsic pharmacology and not from the influence of concomitant psychotropic medications.
Glick
Ira D
ID
Stanford University School of Medicine, Stanford, California, USA.
Zaninelli
Rocco
R
Hsu
Chuanchieh
C
Young
Frederick K
FK
Weiss
Lilia
L
Gunay
Ibrahim
I
Kumar
Vinod
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013405:Suicide / Q000523:psychology; D016896:Treatment Outcome; D000092864:Suicide Prevention
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D011619:Psychotropic Drugs; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine