Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: 1-year results of a randomized controlled trial within the German Research Network on Schizophrenia.
OBJECTIVE
Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested.


METHODS
Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment.


RESULTS
With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups.


CONCLUSIONS
Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment.


BACKGROUND
ClinicalTrials.gov identifier: NCT00159081.
Gaebel
Wolfgang
W
Department of Psychiatry and Psychotherapy, Heinrich-Heine-University of Düsseldorf, Rhineland State Clinics Düsseldorf, Düsseldorf, Germany. wolfgang.gaebel@uni-duesseldorf.de
Riesbeck
Mathias
M
Wölwer
Wolfgang
W
Klimke
Ansgar
A
Eickhoff
Matthias
M
von Wilmsdorff
Martina
M
Jockers-Scherübl
Maria C
MC
Kühn
Kai-Uwe
KU
Lemke
Matthias
M
Bechdolf
Andreas
A
Bender
Stefan
S
Degner
Detlef
D
Schlösser
Ralf
R
Schmidt
Lutz G
LG
Schmitt
Andrea
A
Jäger
Markus
M
Buchkremer
Gerd
G
Falkai
Peter
P
Klingberg
Stefan
S
Köpcke
Wolfgang
W
Maier
Wolfgang
W
Häfner
Heinz
H
Ohmann
Christian
C
Salize
Hans J
HJ
Schneider
Frank
F
Möller
Hans-Jürgen
HJ
D000208:Acute Disease; D000328:Adult; D000465:Algorithms; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D035843:Biomedical Research; D003299:Cooperative Behavior; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life / Q000523:psychology; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D055502:Secondary Prevention; D011795:Surveys and Questionnaires
D014150:Antipsychotic Agents; D006220:Haloperidol; D018967:Risperidone