The long-term clinical benefit and effectiveness of switching to once-daily quetiapine extended release in patients with schizophrenia

Abstract

Objective:

To evaluate the long-term clinical benefit and effectiveness of switching to once-daily quetiapine extended release (XR) from an oral antipsychotic in patients with schizophrenia. Reasons for switching included insufficient efficacy, tolerability, and/or non-acceptability. The primary endpoint was the percentage of patients achieving an improvement in Clinical Global Impression – Clinical Benefit (CGI-CB) scale scores.

Research design and methods:

A 24-week, international, multicentre, open-label, prospective study (www.clinicaltrials.gov: NCT00640601). After a 7–14 day enrolment period (depending whether prior antipsychotic mono- or combination therapy), all patients received quetiapine XR 300 mg once daily (day 1), 600 mg/day (day 2), 600–800 mg/day (day 3) and 400–800 mg/day thereafter, with down-titration and discontinuation of prior antipsychotic by day 4.

Results:

A total of 62% of patients completed the study and 56.9% (LOCF, ITT) achieved a significant improvement in CGI-CB (95% CI [0.51, 0.63]; p = 0.02). Switches due to insufficient efficacy showed a significant improvement (60%, 95% CI [0.51, 0.68]; p = 0.02), compared to 54.4% ([0.44, 0.64]; p = 0.38) and 52.4% ([0.36, 0.68]; p = 0.76) of switches due to insufficient tolerability and non-acceptability respectively (both p = ns). Patients previously on olanzapine and quetiapine IR showed a significant improvement in CGI-CB (62.6% [p = 0.02] and 61.2% [p = 0.04], respectively). Somnolence (18.0%) and dizziness (14.6%) were the main adverse events. Anticholinergic use decreased from 7.1 to 2.7%. Overall mean weight gain was 0.4 kg; 12.9% of patients experienced a weight gain of ≥7% and 15% experienced a clinically relevant shift in triglycerides from baseline.

Conclusions:

A majority of patients switched from other antipsychotics to quetiapine XR experienced clinical benefit. This was supported by all other efficacy outcomes regardless of the reason for switching. Safety data confirmed quetiapine XR was safe and well tolerated. The open-label design and lack of a placebo group represent limitations.

Key words::

• Antipsychotics
• Clinical benefit
• Quetiapine extended release
• Schizophrenia

Transparency

Declaration of funding

This study (D1443L00025) was funded by AstraZeneca Canada Inc. P.C., A.G. and C.S. conceived and designed the study. P.C. was the international principal investigator (PI). With the exception of P.C. and the Astra Zeneca employees (A.G., C.S., H.E.) all the other authors were site PIs in their respective countries. P.C., A.G. and C.S. drafted the initial manuscript with editorial assistance from Christina Clark. P.C., A.G. and C.S. interpreted the results with statistical assistance from Robert Balshaw. All the authors contributed to interpretation of the results and drafting of the manuscript. All the authors reviewed and approved the final version of the manuscript.

Declaration of financial/other relationships

P.C. has received grants, research support, and/or honoraria from Janssen, AstraZeneca, Pfizer, Eli Lilly, Lundbeck, Bristol Myers Squibb, GlaxoSmithKline, Sunovion, Mylan, Valeant, Otsuka and Novartis. A.M. has received financial assistance/compensation for research and education from Pfizer, Janssen, Astra Zeneca and Bristol Myers Squibb. R.-H.B. has been a consultant and/or received funding from pharmaceutical companies including Eli Lilly, Pfizer, AstraZeneca, and Janssen Ortho. S.L. has served as an advisor to pharmacological boards including Lundbeck. S.G., E.S., S.J. and E.C. have no conflicts to report. Y.M.A. has received research grants or served as a lecturer for Janssen, Pfizer, Otsuka, GlaxoSmithKline, Servier, Eli Lilly, Lundbeck, and AstraZeneca. Y.S.K. has received grants, research support, and/or honoraria from Novartis, Janssen, Eli Lilly, Pfizer, Sanofi-Aventis, Otsuka, AstraZeneca, Organon, GlaxoSmithKline and Servier. G.R. has received funding as a speaker from AstraZeneca, Janssen, Eli Lilly, and Lundbeck. C.S., A.G., and H.E. were employees of AstraZeneca at the time of the study.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

We thank Robert Balshaw from Syreon Corporation for statistical assistance, and Christina Clark from MDH Consulting Inc. for editorial assistance; funded by Astra Zeneca Canada Inc. The SPECTRUM XR study group included the following investigators: Dinesh Arya; Gail Robinson (Australia); Pierre Chue; Hubert Colohan; Norman Costigan; Thomas Joseph Raedler; Soma Ganesan; Richard Williams; Redha Mahfoudi; Nizar Ladha; Javed Ali; Ranjith Chandrasena; Leonardo Cortese; Satpal Girgla; Magda Hanna; Rajendra Harricharan; Sunny Johnson; Anil Joseph; Arthur David Kantor; Serge Lessard; Rama Prayaga; Rustom Sethna; Amarendra Singh; Stephen Stokl; Roch-Hugo Bouchard; Guylene Cloutier; Theodore Kolivakis; Ashok Malla; Javad Moamai; Emmanuel Stip; Mohammad Hussain; Mysore Renuka-Prasad (Canada); Eric Chen; Fan Kwong Tsang; Edwin Lee (Hong Kong); Yong Min Ahn; Tae-Youn Jun; Yong Sik Kim; Chang Uk Lee; Kang-Seob Oh; Jung Seo Yi (Republic of Korea).

Previous meeting presentations: Poster presented at the 61st Annual Meeting of the Canadian Psychiatric Association, Vancouver, BC, Canada, Oct 13–15 October 2011.