Answers
10/18/1991

T91-64                                                       Eva Kemper
Oct. 18, 1991                                                (301) 443-3285
<TITLE>ANTIDEPRESSANTS UPDATE</TITLE>
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                              ANTIDEPRESSANTS UPDATE
    Interest continues in reports of an association between the use of        
certain antidepressants, in particular Prozac, and suicidal thoughts and      
acts (suicidality) or other violent behavior.  FDA's Psychopharmacological    
Drugs Advisory Committee met on September 20, 1991, to discuss this matter.
    The following may be used to answer inquiries.
    In the opening public session, the Committee heard testimony from         
patients, advocacy groups, and other interested parties.  Some described      
negative experiences that they attributed to Prozac, while others testified   
in support of Prozac and said that suicidality is a frequent finding in       
depressive illness, unrelated to the medication.
    Following the public comments, an FDA official, citing findings from the  
agency's spontaneous reporting system, pointed out that, despite a large      
number of reports of suicidality in association with use of Prozac, the data  
do not prove a causal relationship, since suicidality can be a manifestation  
of depression.  In addition, a striking surge in spontaneous reports to FDA   
linking Prozac and suicidality occurred following issuance of a report by     
Dr. Martin Teicher of McLean Hospital in Belmont, Mass., in the February      
1990 issue of the American Journal of Psychiatry, suggesting the association  
between the use of Prozac and suicidality.  Reporting rates for suicidality 
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                                            Page 2, T91-64, Antidepressants,
prior to this time, during the first year of marketing, were virtually        
identical for Prozac and Desyrel, another antidepressant first marketed in    
the early 1980's.  The large number of reports of suicidality following the   
Teicher report apparently represented a difference in reporting practices     
for Prozac, not a real difference in the rate of the events themselves.
    An official from the National Institutes of Mental Health (NIMH) also     
argued against the view that the case reports of suicidality in Prozac users  
represented an increased risk.  Pointing out that suicidal thinking is very   
common in depressed people, he showed that, based on known rates, many more   
reports of such thinking would be expected in association with Prozac than    
have been reported.  He also noted that NIMH has a great concern that         
depression is undertreated and that inadequately supported warnings of a      
risk of suicidality with Prozac or other antidepressants would compromise     
efforts to increase the effective treatment of depressive illness.
    While all manufacturers of antidepressant drugs were offered the          
opportunity to present data to the Committee, only Eli Lilly and Co. of       
Indianapolis, Ind., the manufacturer of Prozac, requested time for a          
presentation.  Lilly staff presented data from reanalyses of all of their     
controlled trials involving the use of Prozac in the treatment of             
depression, and of non-mood disorders including obesity, bulimia, and         
obsessive-compulsive disorder.  They compared Prozac-treated and untreated    
groups for rates of suicidal acts and for the emergence of substantial        
suicidal thoughts.  These analyses did not reveal any evidence to support     
the hypothesis that Prozac induces suicidality.  They also presented          
reanalyses of controlled trials looking at measures of aggressiveness and
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                                            Page 3, T91-64, Antidepressants
hostility, and again, did not see any tendency for Prozac use to be           
associated with the emergence of such behaviors.  In fact, Prozac was         
significantly superior to the placebo on these measures.
    The Committee and six additional invited experts were then asked to       
consider whether or not the evidence supported a conclusion that              
antidepressant drugs generally, and Prozac in particular, cause the           
emergence or intensification of suicidality or other violent behaviors.       
They were also asked to consider whether or not any specific agency action    
was warranted, based on the available data.
    The Committee unanimously agreed that there is no credible evidence of a  
causal link between the use of antidepressant drugs, including Prozac, and    
suicidality or violent behavior.  Committee Chairman Daniel E. Casey, M.D.,   
summarized the Committee's view by saying, "There was no evidence showing an  
increase of suicidality with any of the drugs in depressive or nondepressive  
patients.  And regarding Prozac, we probably have looked more closely and     
analytically at those data than on any other antidepressant drug."
    The Committee also voted 6 to 3 against making any change in              
antidepressant labeling on the basis of the available evidence.  However,     
there was a consensus that more research is needed to further explore all     
the potential implications of these reports, not only for Prozac, but for     
other antidepressants as well.  Some members also expressed concern that      
some physicians may fail to properly monitor patients being treated with      
antidepressants.
    Although advisory committee recommendations are not binding on the        
agency, they are given careful consideration in any decisions FDA makes.
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