Indian Journal of PsychiatryIndian Journal of Psychiatry
Home | About us | Current Issue | Archives | Ahead of Print | Submission | Instructions | Subscribe | Advertise | Contact | Login 
    Users online: 2239 Small font sizeDefault font sizeIncrease font size Print this article Email this article Bookmark this page


    Advanced search

    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  


 Article Access Statistics
    PDF Downloaded399    
    Comments [Add]    
    Cited by others 1    

Recommend this journal


LETTER TO EDITOR Table of Contents   
Year : 2010  |  Volume : 52  |  Issue : 1  |  Page : 77
First-generation vs second-generation antipsychotic drugs: The ongoing saga

West Pak Hospital, Darlington, United Kingdom

Click here for correspondence address and email

Date of Web Publication13-Jan-2010

How to cite this article:
Gupta S. First-generation vs second-generation antipsychotic drugs: The ongoing saga. Indian J Psychiatry 2010;52:77

How to cite this URL:
Gupta S. First-generation vs second-generation antipsychotic drugs: The ongoing saga. Indian J Psychiatry [serial online] 2010 [cited 2020 Aug 12];52:77. Available from:


I have read the letter to editor by Dasgupta and Dasgupta with interest. [1] In this year, we have some more publications shedding more light in this area. It is a very intricate area and one should be cautious in interpreting the evidence. Firstly, we have evidences from both efficacy vs effectiveness trial like CATIE (Clinical antipsychotic trials in intervention effectiveness), and CUTLASS (Cost utility of the latest antipsychotics in severe schizophrenia). Effectiveness trials or practical clinical trials are more informative and can easily be applied to practice. Secondly, second-generation antipsychotic drugs (or atypical antipsychotics) are not a homogenous category, they differ both in terms of effects and side effects; hence, when comparing to first-generation drugs, we should be cautious about generalization of the findings. [2] The superiority of clozapine, especially in treatment-resistant patients, has been established. The position of other second-generation antipsychotic drugs, in comparison to first-generation antipsychotic drugs, remains uncertain.

Leucht et al. recently published a meta-analysis of 150 double blind clinical trials, involving 21,533 patients. [3] Four atypical antipsychotic drugs were found to be better than first-generation antipsychotic drugs for overall efficacy (both positive and negative symptoms). Among them, the effect size was largest for clozapine 20.52 (95% CI 20.75 to 20.29, P < 0.0001), which was not surprising. Clozapine was followed by amisulpride 20.31(20.44 to 20.19, P < 0.001), olanzapine 20.28 (20.38 to 0.18, P < 0.0001) and lastly risperidone 20.18 (20.22 to 20.05, P = 0.002). The other second-generation antipsychotics (aripiprazole, quetiapine, zotepine, ziprasidone, sertindole) were not more efficacious than first-generation drugs, even on negative symptoms. Extrapyramidal (EP) symptoms, as expected, were more on first-generation antipsychotic drugs. On the other hand, second-generation antipsychotics drugs (except ziprasidone and aripiprazole) induced more weight gain. Similarly, certain drugs were better for depressive symptoms (amisulpride, clozapine, olanzapine, aripiprazole, and quetiapine). They also showed variable changes in overall efficacy of the individual drug when they compared the efficacy in industry-sponsored or non-sponsored trials.

In March 2009, NICE updated the previous guideline issued in 2002. [4] While in the previous guideline, they had recommended first-line use of atypical antipsychotic drug (second generation).In the current update, due to recent evidence casting doubts about alleged superiority of second-generation antipsychotic drugs, NICE have suggested that selection of the antipsychotic drug should be based on benefit and side-effect profile (EP symptoms vs metabolic side effects).NICE no longer recommends second-generation antipsychotic drugs as a first-line treatment.

The artificial classification of the antipsychotic drugs has caused more harm than benef it. The dichotomy of typical and atypical antipsychotic drugs has been abandoned. The current splitting, first generation and second generation, is also not satisfactory as second generation implies that these drugs are advanced and better than the previous ones. What are the implications of these findings? We should not restrict ourselves to second-generation antipsychotic drugs. In some patients, first-generation antipsychotic drugs may be more effective and better tolerated than the second-generation antipsychotic drugs. The long-term studies with global outcome measures (quality of life, functioning) rather than only symptomatic outcomes will help in understanding the risks and benefits of individual antipsychotic drug.

   References Top

1.Dasgupta R, Dasgupta C. CATIE and CUtLASS (UK): Is it time psychiatrists start changing their practice? The debate goes on!. Indian J Psychiatry 2009;51:161-2.  Back to cited text no. 1      
2.Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry 2009;166:152-63.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: A meta-analysis. Lancet 2009;373:31-41.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.National Institute for Clinical Excellence. Core interventions in the treatment and management of schizophrenia in primary and secondary care (update). March 2009, London.  Back to cited text no. 4      

Correspondence Address:
Sumeet Gupta
West Pak Hospital, Darlington
United Kingdom
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5545.58904

Rights and Permissions

This article has been cited by
1 A common gene expression signature in Huntington¿s disease patient brain regions
Andreas Neueder,Gillian P Bates
BMC Medical Genomics. 2014; 7(1): 60
[Pubmed] | [DOI]