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Letters to the Editor |

First- vs Second-Generation Antipsychotic Drugs in Schizophrenia

Chittaranjan Andrade, MD; Saifuddin Kharawala, DPM
Arch Gen Psychiatry. 2007;64(8):978-979. doi:10.1001/archpsyc.64.8.978-b.
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The Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1)1 found that, in patients with schizophrenia whose medication was changed for clinical reasons, first (FGA)- and second (SGA)-generation antipsychotics were associated with comparable 1-year outcomes on measures of clinical improvement, adverse effects, quality of life, and costs of care. We have several concerns about the study:

  1. During the study, 55 of 118 patients (47%) switched from an FGA to an SGA, but only 36 of 109 (33%) switched from an SGA to an FGA (Figure 11[p1081]); the advantage for the SGA was statistically significant (χ21 = 4.35; P < .05). The most commonly prescribed FGA and SGA were sulpiride and olanzapine, respectively; the 1-year persistence rates for these drugs were 28 of 58 (48%) and 37 of 50 (74%), respectively. The advantage for olanzapine was statistically significant (χ21 = 7.42; P < .001). Neither analysis was presented in the article.

  2. The sample was poorly treatment responsive; at 1 year, the average patient showed less than 10% improvement in the Positive and Negative Syndrome Scale total score. Therefore, a floor effect may have prevented the identification of differential effectiveness of the medications. A previous study,2 which compared olanzapine and haloperidol across 1 year, also failed to find an effectiveness difference between the 2 drugs for likely similar reasons.

  3. Most clinicians and educated patients probably believe that the SGAs are better than the FGAs. The referral and consenting procedures could therefore have loaded the sample with 2 types of patients: those who had previously responded to and tolerated an FGA and those who had previously not responded to or not tolerated an SGA. In other words, there could have been a hidden bias in favor of the FGA and against the SGA.

  4. Twelve FGA patients were prescribed a depot drug from the outset; the consequently better compliance may have biased the results in favor of the FGA group. Additionally, by the end of the study, 6 more FGA patients and 17 SGA patients were receiving depot preparations. If poor medication compliance was a patient characteristic and was responsible for the switch from SGA to depot medication, outcomes (before the switch) with the SGA could have been compromised and the use of FGA depot drugs by SGA patients could have further decreased the likelihood of statistical separation of the groups in at least some of the analyses.

  5. Sulpiride was the most commonly prescribed FGA (in 49% of the FGA group). However, this drug is closer to the atypical antipsychotics than to the neuroleptics in its clinical profile.3 Therefore, readers should not assume that the favorable outcomes with the FGA mean that all FGAs in general, and the neuroleptics in particular, are just as effective and as well tolerated as the atypical antipsychotics.

  6. Finally, the ecological validity of the study may be limited to countries with a social and health care structure similar to that of the United Kingdom. This is because outcomes with antipsychotic drugs depend not only on the drugs but also on factors such as levels of social and family stress and social and family support.


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