Placebo response in clinical trials with schizophrenia patients.

PURPOSE OF REVIEW: The magnitude of placebo response is an important factor in the outcome of clinical trials, in that excessive placebo response can obscure true drug-placebo differences. There is ample evidence of the impact of elevated placebo response in trials of major depression, but less intensive research has been done in the area of schizophrenia. We present a current review of placebo response in clinical trials of schizophrenia. RECENT FINDINGS: The existing evidence suggests that placebo response in schizophrenia trials may be similar in magnitude, quality, and impact to that observed in depression trials, and has similarly increased over the past several years. We discuss factors influencing excessive placebo response during the conduct of clinical trials and how they may be managed to help minimize placebo response. SUMMARY: There does not appear to be any single major factor contributing to the high levels of placebo response in schizophrenia clinical trials; therefore, a multipronged approach to minimizing excessive placebo response or its impact is recommended.

Triglyceride/high-density lipoprotein cholesterol ratio: a surrogate to predict insulin resistance and low-density lipoprotein cholesterol particle size in nondiabetic patients with schizophrenia.

OBJECTIVE: Insulin resistance, changes in lipid parameters, and cardiometabolic adverse events have been reported in some patients during clinical trials of antipsychotic agents. The present study examined whether the triglyceride/high-density lipoprotein (HDL) ratio can be used as a better surrogate than other conventional lipid measures (low-density lipoprotein [LDL], HDL, triglyceride) in predicting insulin resistance and LDL particle size in nondiabetic patients with schizophrenia. METHOD: Outpatients 18 to 75 years old diagnosed with schizophrenia or schizoaffective disorder (DSM-IV criteria) and receiving olanzapine, risperidone, or typical antipsychotics participated in a multicenter, cross-sectional study. Fasting blood samples were obtained to determine the levels of glucose, insulin, lipids, and lipid particle size. The study was conducted from July 2001 to March 2002. RESULTS: In the sample of 206 patients, significant correlations were found between various lipid measures (LDL, HDL, triglyceride, and triglyceride/HDL ratio) and the homeostasis model of assessment of insulin resistance (P < .05). However, stepwise multiple regression analysis suggested that the triglyceride/HDL ratio is a stronger predictor of insulin resistance and of LDL particle size than other conventional lipoprotein measures after other potential confounding variables, including age, gender, race, family history of diabetes, body mass index, and antipsychotic agent, were taken into consideration (P < .001). Further, logistic regression analysis indicated that the triglyceride/HDL ratio and male gender predict the existence of a small LDL particle size pattern (pattern B LDL phenotype), with a sensitivity of 75.9% and a specificity of 85.4%. CONCLUSIONS: The triglyceride/HDL ratio, a simple, readily available and inexpensive measure, can be a useful surrogate to identify those with insulin resistance as well as those with more atherogenic small LDL particles in nondiabetic patients with schizophrenia.