Dosing quetiapine in drug-naive first-episode psychosis: a controlled, double-blind, randomized, single-center study investigating efficacy, tolerability, and safety of 200 mg/day vs. 400 mg/day of quetiapine fumarate in 141 patients aged 15 to 25 years.
OBJECTIVE
To assess dosing, efficacy, and tolerability of quetiapine fumarate in drug-naive first-episode psychosis.


METHODS
We present a prospective, randomized, controlled, single-center, double-blind, fixed-dose, 4-week comparison study of 200 mg/day versus 400 mg/day of quetiapine in 141 drug-naive acutely ill first-episode psychosis patients (diagnosed according to DSM-IV) aged 15 to 25 years. The double-blind 4-week trial (Part 1) was followed by a single-blind, naturalistic, flexible-dose 8-week period (Part 2). The main outcome measures were symptomatic change, functioning, and tolerability. Data were collected from July 2003 until January 2006.


RESULTS
The estimated time trends of the linear mixed-effects modeling indicated that efficacy between the 2 treatment groups in Part 1 was similar for most outcome measures except for 5 measures: the Scale for the Assessment of Negative Symptoms (SANS) anhedonia-asociality subscale (p = .011), the Social and Occupational Functioning Assessment Scale (p = .020), the Global Assessment of Functioning scale (p = .070), the SANS affective flattening or blunting subscale (p = .051), and the Udvalg for Kliniske Undersogelser total (p = .056), suggesting that the 200-mg group improved more for the SANS anhedonia-asociality subscale, whereas the 400-mg group showed a slight deterioration. Social and global functioning also improved more in the 200-mg group than in the 400-mg group. Part 2 of the study revealed that, independent of the initial target dose, when clinicians were able to adjust the dose flexibly, the dose at 12 weeks was similar between groups and averaged 268 mg/day.


CONCLUSIONS
Our study in acutely ill drug-naive first-episode psychosis patients suggests that quetiapine is a safe and well-tolerated antipsychotic medication. In contrast to multiepisode patients, dosing should be more conservative in untreated new-onset cases. An initial dose of 250 to 300 mg/day of quetiapine is proposed as a primary target dose in drug-naive first-episode psychosis patients.


BACKGROUND
clinicaltrials.gov Identifier: NCT00449397.
Berger
Gregor E
GE
The Schloessli Clinic, Department of Research and Education, Schlösslistrasse 8, CH-8618 Oetwil am See, Switzerland. bergerg@mac.com
Proffitt
Tina-Marie
TM
McConchie
Mirabel
M
Kerr
Melissa
M
Markulev
Connie
C
Yuen
Hok Pan
HP
O'Donnell
Colin
C
Lubman
Dan
D
Polari
Andrea
A
Wood
Stephen
S
Amminger
Paul G
PG
McGorry
Patrick D
PD
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D016014:Linear Models; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000188:drug therapy*; D000069348:Quetiapine Fumarate
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate