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Letters to the Editor   |    
Response to Nasrallah Letter
Helen C. Kales, M.D.; Frederic C. Blow, Ph.D.; Lon S. Schneider, M.D., M.S.
Am J Psychiatry 2012;169:664-665. doi:10.1176/appi.ajp.2012.12020279r
View Author and Article Information
Ann Arbor, Michigan
Los Angeles

The authors' disclosures accompany the original article.

Accepted for publication in March 2012.

Copyright © American Psychiatric Association

Accepted March , 2012.

To the Editor: As Dr. Nasrallah notes, our data provide confirmation of the higher mortality associated with haloperidol when compared with atypical antipsychotics in patients with dementia (1). The main finding and unique contribution of our paper, however, is that there are mortality risk differences between atypical antipsychotics, with risperidone and olanzapine having higher mortality rates than quetiapine. Since the publication of our article, our findings of differential mortality among individual antipsychotics have been confirmed in another sample (2).

Dr. Nasrallah also brings his pilot study (3) to our attention. This retrospective study at a single center reported higher rates of 2-year mortality for patients taking haloperidol in comparison with those taking atypical antipsychotics. However, as noted in a letter to the editor regarding that paper (4), the study did not control for the known selection biases that occur in patients treated with haloperidol compared with atypical antipsychotics. Haloperidol tends to be prescribed for patients older and sicker than those treated with atypical antipsychotics (5). In our study, we analyzed a wide array of potential confounding factors in addition to using propensity methods to control for potential treatment-by-indication bias. In doing so, we observed the mortality action of haloperidol occurring within the first 30 days of treatment. Therefore, it is unclear that one could conclude that neurotoxicity is the mechanism of mortality risk.

In light of our data, the evidence from randomized controlled trials, and a number of retrospective database studies, we find no support for the idea that atypical antipsychotics are neuroprotective in patients with dementia. Randomized trials have shown atypical antipsychotics to have 1%–2% higher risk than placebo over 10- to 12-week study periods (6). Over the longer 6-month follow-up in our cohort, olanzapine and risperidone showed mortality rates of approximately 27 deaths per 100 person-years of treatment compared with 18.6–21 deaths per 100 person-years with quetiapine and valproic acid. In addition, we previously showed (7) that the absolute mortality risk over 12 months in patients taking atypical antipsychotics was 4.8% higher than in those not taking medication, which corresponds to a number needed to harm of 20.8. Therefore, if atypical antipsychotics are to be prescribed, then they should be used in conjunction with a risk-benefit approach taking into account the efficacy and safety evidence base for the agents under consideration.

Kales  HC;  Kim  HM;  Zivin  K;  Valenstein  M;  Seyfried  LS;  Chiang  C;  Cunningham  F;  Schneider  LS;  Blow  FC:  Risk of mortality among individual antipsychotics in patients with dementia.  Am J Psychiatry 2012; 169:71–79
[PubMed]
 
Huybrechts  KF;  Gerhard  T;  Crystal  S;  Olfson  M;  Avorn  J;  Levin  R;  Lucas  JA;  Scheeweiss  S:  Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population-based cohort study.  BMJ 2012; 344:e977
[PubMed]
[CrossRef]
 
Nasrallah  HA;  White  T;  Nasrallah  AT:  Lower mortality in geriatric patients receiving risperidone and olanzapine versus halo-peridol: a preliminary analysis of retrospective data.  Am J Geriatr Psychiatry 2004; 12:437–439
[PubMed]
 
Blazer  DG:  Comment on Nasrallah et al: lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol.  Am J Geriatr Psychiatry 2004; 12:658–659
[PubMed]
 
Kim  HM;  Chiang  C;  Kales  HC:  After the black box warning: predictors of psychotropic treatment choices for older patients with dementia.  Psychiatr Serv 2011; 62:1207–1214
[PubMed]
[CrossRef]
 
Schneider  LS;  Dagerman  KS;  Insel  P:  Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.  JAMA 2005; 294:1934–1943
[PubMed]
[CrossRef]
 
Kales  HC;  Valenstein  M;  Kim  HM;  McCarthy  J;  Ganoczy  D;  Cunningham  F;  Blow  F:  Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications.  Am J Psychiatry 2007; 164:1568–1576
[PubMed]
[CrossRef]
 
References Container
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References

Kales  HC;  Kim  HM;  Zivin  K;  Valenstein  M;  Seyfried  LS;  Chiang  C;  Cunningham  F;  Schneider  LS;  Blow  FC:  Risk of mortality among individual antipsychotics in patients with dementia.  Am J Psychiatry 2012; 169:71–79
[PubMed]
 
Huybrechts  KF;  Gerhard  T;  Crystal  S;  Olfson  M;  Avorn  J;  Levin  R;  Lucas  JA;  Scheeweiss  S:  Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population-based cohort study.  BMJ 2012; 344:e977
[PubMed]
[CrossRef]
 
Nasrallah  HA;  White  T;  Nasrallah  AT:  Lower mortality in geriatric patients receiving risperidone and olanzapine versus halo-peridol: a preliminary analysis of retrospective data.  Am J Geriatr Psychiatry 2004; 12:437–439
[PubMed]
 
Blazer  DG:  Comment on Nasrallah et al: lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol.  Am J Geriatr Psychiatry 2004; 12:658–659
[PubMed]
 
Kim  HM;  Chiang  C;  Kales  HC:  After the black box warning: predictors of psychotropic treatment choices for older patients with dementia.  Psychiatr Serv 2011; 62:1207–1214
[PubMed]
[CrossRef]
 
Schneider  LS;  Dagerman  KS;  Insel  P:  Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.  JAMA 2005; 294:1934–1943
[PubMed]
[CrossRef]
 
Kales  HC;  Valenstein  M;  Kim  HM;  McCarthy  J;  Ganoczy  D;  Cunningham  F;  Blow  F:  Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications.  Am J Psychiatry 2007; 164:1568–1576
[PubMed]
[CrossRef]
 
References Container
+
+

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