Generalizability of the results of efficacy trials in first-episode schizophrenia: comparisons between subgroups of participants of the European First Episode Schizophrenia Trial (EUFEST).
OBJECTIVE
Most randomized drug trials in schizophrenia exclude patients with comorbidities such as suicidality or substance use, which may limit the generalizability of the results. We aimed to evaluate the generalizability of the results of these trials in participants of a randomized clinical trial with broad inclusion criteria.


METHODS
In 50 sites in 14 countries, 498 patients with first-episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder) were recruited between December 2002 and January 2006 in an open, randomized clinical drug trial with 12 months of follow-up. Baseline characteristics and follow-up data were compared between patients with versus patients without baseline suicidality and/or substance use.


RESULTS
Of the 489 participants with data on baseline suicidality and substance use, 153 (31%) patients were suicidal and/or using substances. Groups differed on only a few of the many baseline characteristics tested: comorbid patients were younger (25.1 vs 26.5 years of age; P < .01), less often female (25% vs 47%; P < .001) or married (4% vs 17%; P < .001), had fewer years of education (11.8 vs 12.8; P < .001), and experienced lower levels of overall psychosocial functioning (Global Assessment of Functioning; 38.4 vs 40.8; P <or= .05) and higher levels of depression (Calgary Depression Scale for Schizophrenia; 6.1 vs 4.6; P < .001). At follow-up, comorbid patients showed shorter time to (re)hospitalization and reported higher levels of depression than patients without comorbidity (hazard ratio = 2.02, P = .004; chi(2)(7) = 17.25, P = .016, respectively), without differences on other outcome measures.


CONCLUSIONS
Although it appears that the generalizability of antipsychotic treatment trials in first-episode patients is not seriously affected by the exclusion of patients with suicidal symptoms and/or substance use, researchers should be cautious about the exclusion of such patients.


BACKGROUND
controlled-trials.com Identifier: ISRCTN68736636.
Boter
Han
H
Department of Epidemiology (room FA 40), University Medical Centre Groningen, PO Box 30001, NL-9700 RB Groningen, The Netherlands. H.Boter@epi.umcg.nl
Derks
Eske M
EM
Fleischhacker
W Wolfgang
WW
Davidson
M
M
Kahn
René S
RS
D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010349:Patient Compliance; D018579:Patient Selection; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000150:complications; D013406:Suicide, Attempted / Q000523:psychology
D014150:Antipsychotic Agents