Rapid Versus Conventional Initiation of Quetiapine in the Treatment of Schizophrenia: A Randomized, Parallel-Group Trial

Chi-Un Pae, M.D.; Jung-Jin Kim, M.D.; Chang-Uk Lee, M.D.; Soo-Jung Lee, M.D.; Chul Lee, M.D.; Ashwin A. Patkar, M.D.; Prakash S. Masand, M.D.; and In-Ho Paik, M.D.

Objectives: The primary objective of this study was to compare the safety and tolerability of a rapid initiation of quetiapine with the conventional initiation approved by the U.S. Food and Drug Administration (FDA). The secondary objectives included assessment of the efficacy of a rapid initiation of quetiapine compared with a conventional initiation approved by the FDA.

Method: Patients with acute schizophrenia were randomly assigned in a 3:1 ratio to the rapid-initiation group (200 mg on day 1, 400 mg on day 2, 600 mg on day 3, and 800 mg on day 4) or to the conventional-initiation group (50 mg on day 1, 100 mg on day 2, and increased in 100 mg/day increments to reach 400 mg on day 5). The tolerability measures were Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS) as well as all adverse events at day 1, 2, 3, 4, 5, 6, and 7 and at day 14. Standard efficacy measures were administered at baseline, day 1, day 4, day 5, day 7, and day 14. These measures consisted of the Positive and Negative Syndrome Scale (PANSS), PANSS-Excited Component (EC), and Clinical Global Impressions-Severity of Illness (CGI-S) scale.

Results: Forty patients were randomly assigned to treatment. The mean (SD) dose of quetiapine at study end point was 763.3 (106.6) and 600.0 (249.4) mg/day in the rapid-initiation group and conventional-initiation group, respectively. The most common side effects were sedation and dizziness, with no significant differences in frequency between groups. Only 2/30 patients from the rapid-initiation group discontinued treatment due to an adverse event (both for sedation), and 1/10 patients from the conventional-initiation group discontinued before receiving quetiapine. Neither serious adverse events nor differences between groups in vital signs, laboratory assessments, ECG measures, or weight changes were reported. Rapid initiation of quetiapine was generally well-tolerated and was associated with a faster onset of action than conventional initiation as measured by improvement in psychotic symptoms at days 4 and 5.

Conclusion: This study may offer preliminary evidence for tolerability and effectiveness in rapid dose initiation of quetiapine in the treatment of schizophrenia.

(J Clin Psychiatry 2007;68:399-405)

Received Feb. 18, 2006; accepted June 26, 2006. From the Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea (Drs. Pae, Kim, C.-U. Lee, S.-J. Lee, C. Lee, and Paik); and the Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, N.C. (Drs. Pae, Patkar, and Masand).

AstraZeneca provided support for this investigator initiated trial (Drs. Pae and Paik).

Presented as a poster at the 18th European College of Neuropsychopharmacology Congress, October 22-26, 2005, Amsterdam, the Netherlands.

The authors thank Mr. J. Collis from Complete Medical Communications Ltd., who provided medical writing support on behalf of AstraZeneca.

Dr. Pae has received research support from GlaxoSmithKline. Dr. Patkar is a consultant for Bristol-Myers Squibb, GlaxoSmithKline, and Reckitt Benckiser; has received research support from the National Institutes of Health, AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, McNeil Consumer and Specialty Pharmaceuticals, Organon, Jazz Pharmaceuticals, and Pfizer; and is on the speakers bureaus for Bristol-Myers Squibb, GlaxoSmithKline, and Reckitt Benckiser. Dr. Masand is a consultant for Bristol-Myers Squibb, Forest, GlaxoSmithKline, Health Care Technology, Janssen, Jazz Pharmaceuticals, Organon, Pfizer, and Wyeth; has received research support from AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, Ortho-McNeil, and Wyeth; is on the speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, Pfizer, and Wyeth; and is a stockholder in psychCME. Drs. Kim, C-U. Lee, S-J. Lee, C. Lee, and Paik report no financial affiliations or other relationships relevant to the subject of this article.

Corresponding author: Chi-Un Pae, M.D., Department of Psychiatry, The Catholic University of Korea College of Medicine, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea (e-mail:pae@catholic.ac.kr). Reprints: In-Ho Paik, M.D. (e-mail: nppih@catholic.ac.kr).