Thirty-one subjects consented for the study with 25 subjects randomized to either ramelteon 8 mg/day or placebo in a 2:1 fashion. Five subjects withdrew consent following randomization but prior to the week 4 assessment (2 ramelteon and 3 placebo). Data from 20 subjects is presented. Baseline demographics are presented in .There were no differences between the placebo and ramelteon groups for mean age, gender, ethnicity or antipsychotic drug use. Four subjects in the ramelteon group were treated with two antipsychotic agents compared to one subject in the placebo group ().
Demographic and clinical characteristics, comparing ramelteon 8 mg/day to placebo in an 8-week pilot study in subjects with schizophrenia
Anthropometric measurements and DEXA
Anthropometric measurements at baseline did not differ in the placebo group compared to the ramelteon group. There was no significant difference between groups comparing week 8 values, controlling for baseline for body weight, BMI, waist circumference, waist-hip ratio, and skin fold total, and ideal body weight (). Though not statistically significant, there was a decrease in the ramelteon group compared to the placebo group in mean change in abdominal fat (p=.07, effect size=.88), trunk fat (p=.45, effect size= .40), percent abdominal fat (p=.18, effect size=.72) and percent trunk fat (p=.29, effect size= .56) at week 8 controlling for baseline (). While there was a non-significant increase in lean abdominal mass and trunk mass in the ramelteon group, there was a decrease in these measures in the placebo group. Overall the abdominal (p=.44) and trunk mass (fat and lean) (p=.44) non-significantly decreased in the ramelteon group while it increased in the placebo group.
Outcome measures comparing ramelteon 8mg/day to placebo in an 8-week pilot study in subjects with schizophrenia
DEXA scan results, comparing ramelteon 8mg/day to placebo in an 8-week pilot study in subjects with schizophrenia
Glucose metabolism and inflammatory marker
The ramelteon group had non-significant reductions in fasting serum insulin level (p= .29, effect size= 0.6) and HOMA-IR (p=.34, effect size =.54) compared to placebo (). The ramelteon group had a greater decrease in C-reactive protein but this was not significant (p=.55).
The ramelton group showed a significant decrease in total cholesterol and cholesterol to HDL ratio (p=.03 and .01, respectively) (). LDL-cholesterol decreased in the ramelteon group but was not significant (p=.10, effect size= .76). There was a significant reduction in LDL particle number in the ramelteon group (1785± 513 nmol/L to 1626± 606 nmol/L; effect size=0.53; p=0.03). There was a non-significant reduction in small LDL in the ramelteon group and trend toward an increase in LDL-C particle size in the ramelteon group (20.77± 0.99 nm to 20.81± 0.8 nm; effect size= .49; p= .36). The decrease in small LDL particle number and the increase in LDL-C particle size suggest improvements in atherogenic LDL-cholesterol in the ramelteon group.
Psychopathology, sleep quality, and side effects
There were no significant changes in psychopathology in either group from the baseline to week 8. Examining changes in sleep, the ramelteon group experienced a trend toward less daytime fatigue (p=.05, effect size=1.08) and fewer days that they felt fatigued (p=.09, effect size = 1.27) compared to placebo. Frequently observed side-effects, compared to placebo, during the study were drowsiness (57% vs. 33%), heart burn (21% vs. 0%), cough (21% vs. 0%), akathisia (21% vs. 0%), increased urinary frequency (14% vs. 0%), and problems with memory or concentration (21% vs. 0%). The placebo group experienced arthralgia/myalgia and anxiety at significantly higher rates than the ramelteon group.