Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia

Irving Kuo, MD


January 18, 2007

Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1)

Jones PB, Barnes TRE, Davies L, et al.
Arch Gen Psychiatry. 2006;63:1079-1087


The impact of first-generation antipsychotic medications (FGAs) vs second-generation antipsychotic medications (SGAs) on quality of life was evaluated. Secondary outcomes included:

  • Symptom improvement;

  • Adverse effects;

  • Patient satisfaction; and

  • Healthcare costs.

A total of 227 individuals with a diagnosis of schizophrenia, schizoaffective disorder, or delusional disorder were randomized to receive either FGAs or SGAs. Following randomization, the referring psychiatrists would choose a medication from the assigned class to administer for up to 1 year's duration. The primary outcome measure was total score on the Quality of Life Scale (QLS), assessed blindly at baseline and at Weeks 12, 26, and 52 of the study. Secondary outcome measures included:

  • Positive and Negative Syndrome Scale (PANSS);

  • Calgary Depression Scale;

  • Various scales looking at adverse medication effects; and

  • Participant satisfaction.

SGAs included:

The most commonly used FGA was sulpiride, used in Great Britain since the 1960s and considered to be a low-potency agent with a lower risk for extrapyramidal symptoms compared with other FGAs.

SGAs did not show superiority in improvement in the QLS. In fact, there was a numerical trend toward greater improvement with the FGA cohort. Healthcare costs were similar in both groups with psychiatric inpatient hospitalization responsible for the majority of the expense. Although SGAs were more expensive than FGAs, total antipsychotic medication cost was a relatively small proportion of total expenses (2.1% and 3.8% for FGAs and SGAs, respectively). There was no measurable difference between the 2 cohorts in:

  • Positive or negative symptoms;

  • Depressive symptoms; or

  • Adverse effects.



This study, which has several strengths listed below, further muddies the waters:• It is not sponsored by a pharmaceutical company;

  • It is consistent with several other recent studies showing minimal to no clinical or cost-savings advantage of SGAs over FGAs[1,2];

  • It is a pragmatic, blinded, well-designed trial that contains thoughtful discussion about why the original premise (namely, SGA superior to FGA) could not be proven; and

  • Effect size, sample size, statistical power, utility of the QLS, and possible participant (patient, psychiatrist, and researcher) biases were all assessed, and none of these factors seems to fully explain the results.

Despite its strengths, this study fails to answer definitely key questions: Are second-generation antipsychotic medications overrated? Do they really provide patients with a distinct advantage over first-generation antipsychotics?

Perhaps what we are seeing is that neither FGAs nor SGAs are precisely what we need for symptom and functional improvement in the treatment of schizophrenia and other psychotic disorders. Further studies on new pharmacologic modalities as well as nonpharmacologic rehabilitative treatment models need to be pursued to help optimize treatment for this population.



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