Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia.
OBJECTIVE
After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia.


METHODS
A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits).


RESULTS
Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects.


CONCLUSIONS
Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases.


BACKGROUND
clinicaltrials.gov Identifier: NCT00159120.
Gaebel
Wolfgang
W
Department of Psychiatry and Psychotherapy, Heinrich-Heine-University, Düsseldorf, Rhineland State Clinics Düsseldorf, Bergische Landstraße 2, D-40629 Düsseldorf, Germany. wolfgang.gaebel@uni-duesseldorf.de
Riesbeck
Mathias
M
Wölwer
Wolfgang
W
Klimke
Ansgar
A
Eickhoff
Matthias
M
von Wilmsdorff
Martina
M
Lemke
Matthias
M
Heuser
Isabella
I
Maier
Wolfgang
W
Huff
Wolfgang
W
Schmitt
Andrea
A
Sauer
Heinrich
H
Riedel
Michael
M
Klingberg
Stefan
S
Köpcke
Wolfgang
W
Ohmann
Christian
C
Möller
Hans-Jürgen
HJ
D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010353:Patient Education as Topic; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012569:Schizotypal Personality Disorder / Q000188:drug therapy* / Q000523:psychology; D055502:Secondary Prevention
D014150:Antipsychotic Agents; D006220:Haloperidol; D018967:Risperidone