TY - JOUR
T1 - Changes in serum lipids, independent of weight, are associated with changes in symptoms during long-term clozapine treatment
AU - Procyshyn, Ric M.
AU - Wasan, Kishor M.
AU - Thornton, Allen E.
AU - Barr, Alasdair M.
AU - Chen, Eric Y.H.
AU - Pomarol-Clotet, Edith
AU - Stip, Emmanuel
AU - Williams, Richard
AU - MacEwan, G. William
AU - Birmingham, C. Laird
AU - Honer, William G.
N1 - Funding Information:
Competing interests: Dr. Procyshyn has received consulting or advisory board fees and lecture fees from AstraZeneca, GlaxoSmithKline, Janssen and Eil Lilly. Dr. Chen has recieved grant funding from AstraZeneca. Dr. Stip has recieved consulting or advisory board fees from AstraZeneca, Janssen and Eli Lilly; Pfizer lecture fees from AstraZeneca, Janssen and Eli Lilly; and grant funding from AstraZeneca. Dr. Williams has received consulting or advisory board fees from AstraZeneca, Genpharm, Janssen, Eli Lilly and Prestwick Pharmaceuticals; lecture fees from AstraZeneca, Genpharm, Janssen, Eli Lilly, Novartis, Pfizer and Prestwick Pharmaceuticals; and grant funding from AstraZeneca, Janssen and Pfizer. Dr. MacEwan has received consulting or advisory board fees from AstraZeneca, Janssen, Eli Lilly and Novartis; lecture fees from GlaxoSmithKline; and grant support from AstraZeneca. Dr. Honer has received consulting or advisory board fees from In Silico Biosciences, Janssen, and Wyeth and lecture fees from AstraZeneca.
Funding Information:
Supported by a grant from the Stanley Medical Research Institute. Risperidone and placebo were provided by Janssen-Ortho, Canada. Additional support was provided by the British Columbia Mental Health and Addictions Services and the Michael Smith Foundation for Health Research. We thank Dr. Jiri Frolich, MD, University of British Columbia, for his consultation and review of the manuscript and Dr. Raymond Koopman, Simon Fraser University, for his stastical consultation. The following institutions and investigators participated in the Clozapine and Risperidone Enhancement Study Group: Castle Peak Hospital, Hong Kong, China: S.P. Leung and J.O.Y Wong; Centre de Recherche Fernand-Seguin, Montréal: J.P. Rodriguez, P. Lalonde and E. Stip; Fulbourn Hosptial, Cambridge, UK: E. Pomarol-Clotet and P.J. McKenna; Peace Arch Hospital, White Rock, B.C; G.W. MacEwan; Queen Mary Hospital, Hong Kong, China: E.Y.H. Chen and R.C.K. Chan; Riverview Hospital, Port Coquitlam, BC: S.W. Flynn, S. Altman, W.G. Honer, A.E. Thornton, R. M. Procyshyn, S. Huckin, T. Au, V. Boudreau and B. Humphries; Royal Jubilee Hospital, Victoria, BC: R. Williams; University of British Columbia, Vancouver, BC: K. Wasan; University Clinic, Hamburg, Germany: A. Bergmann, P. Falkai, T. Wobrock and H. Wollny.
PY - 2007/9
Y1 - 2007/9
N2 - Objective: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. Methods: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. Results: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. Conclusion: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity.
AB - Objective: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. Methods: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. Results: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. Conclusion: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity.
KW - Cholesterol
KW - Clozapine
KW - Lipids
KW - Triglycerides
UR - http://www.scopus.com/inward/record.url?scp=34848827473&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34848827473&partnerID=8YFLogxK
M3 - Article
C2 - 17823649
AN - SCOPUS:34848827473
SN - 1180-4882
VL - 32
SP - 331
EP - 338
JO - Journal of Psychiatry and Neuroscience
JF - Journal of Psychiatry and Neuroscience
IS - 5
ER -