Are patients enrolled in first episode psychosis drug trials representative of patients treated in routine clinical practice?

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Abstract

Background: Evidence on efficacy of antipsychotic medications comes primarily from controlled trials which select eligible consenting patients for experimental and regimented treatments, who do not abuse drugs, and are in good general health. Thus, it is not clear to what extent results are generalizable to most individuals treated for a psychotic illness who may not be eligible for such trials. Objective: This study compared characteristics of patients treated in a large randomized trial of persons with early psychosis to a cohort from a large epidemiological study of first episode psychosis. Methods: Included were the 535 patients enrolled in a controlled trial of antipsychotic medication and 179 similarly diagnosed persons from the Suffolk County Mental Health epidemiological study. Drug trial exclusion criteria were used to estimate the number of patients from the epidemiological study who would have been ineligible for the drug trial. The two samples were compared on key characteristics. Results: Thirty-three percent (n=59) of the epidemiological sample did not meet inclusion criteria for the drug trial (due to antidepressant treatment, n=26; current substance abuse, n=18; recent suicide attempt, n=9; and for more than one reason, n=6). There were no significant differences between the two study samples on age of onset, age, gender and premorbid functioning. Drug trial patients had higher Brief Psychiatric Rating Scale (BPRS), slightly lower Clinical Global Impression (CGI), and less formal education than those in the epidemiological study. Conclusions: While some patients in the epidemiological sample would have been excluded from the drug trial, patients in the two studies were similar on several key variables.

Section snippets

Background

Evidence on the efficacy of pharmacotherapies in treating psychotic disorders comes primarily from randomized controlled drug trials. Since these trials carefully select eligible patients who consent to participate in regimented treatment programs they offer a high degree of internal validity but have unknown external validity or generalizability (Pocock, 1983), which needs to be established Dans et al., 1998, Olschewski et al., 1992.

The evidence from such drug trials suggests that

Samples

The data for this paper were drawn from two sources, a countywide epidemiological study of first episode psychosis, the Suffolk County Mental Health Project, and a multi-country randomized controlled trial of risperidone versus haloperidol in first episode psychosis. Both studies were conducted according to the relevant IRB and good clinical practice rules.

Results

One-third (n=59 out of 179) of the Suffolk County patients would not have been eligible for the drug trial. The most common reason was current treatment with antidepressant medication (n=26, 34%), substance abuse during current month (n=15, 25.4%), current alcohol abuse (n=2, 3.3%), suicide attempt (n=9, 15.2%), current alcohol and drug abuse (n=1, 1.7%), antidepressant use and suicide attempt (n=1, 1.7%), substance abuse and antidepressant use (n=1, 1.7%), substance abuse and suicide attempt (n

Discussion

The results of this study suggest that, while some of the patients from the epidemiological cohort would have not met criteria for the drug trial, primarily because they were taking antidepressants, the patients in the two studies were similar. Perhaps the most direct test of the effect of the exclusion criteria and artifice of the drug trial is the comparison of the Suffolk County drug trial patients to the Suffolk county epidemiological cohort that consisted of different patients from the

Acknowledgements

The randomized controlled drug trial presented in this paper was conducted by Janssen Research Foundation. The study included the following investigators and locations: Australia—P. McGorry (Melbourne); T. Lambert (Bentley); J. Kulkarni (Dandenong); Austria—W. Fleischhacker (Innsbruck); Canada—D. Addington (Calgary); L. Kopala (Halifax); R. Williams (Calgary); G. Chouinard (Montreal); A. Labelle (Ottawa); A. Malla (London); S. Purdon (Edmonton); M. Saxena (Hamilton); V. Nair (Montreal); R.

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