Metabolic Effects of Two Different Doses of Venlafaxine Therapy on Rats

Objectives: Venlafaxine is an antidepressant, categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI) with suspected metabolic side effects. The aim of our study was to assess these metabolic effects in rats, using two different doses of venlafaxine.
Materials: Three groups of Wistar rats have been treated with venlafaxine during seven weeks. The rats have received a daily dose of 10mg/kg (D1) and 40 mg/kg (D2) while the control group (Dc) has received no treatment. Rats were given “ad libitum” access to food and water. The rats were weighted at treatment day 0, 7, 14, 21, 28, 35, 42 and 49. After completion of venlafaxine treatment, the rats were sacrificed, blood was harvested and the following biochemical parameters have been determined from the centrifuged plasma: triglycerides, glucose and total cholesterol levels.
Results: Both the 10 mg/kg and the 40 mg/kg dose venlafaxine therapy resulted in a highly significant increase of rat’s weight. Compared with the control group the mean weight of D1 group has increased with 130.5 ±21.79 g (<0.01) while the mean weight of the second group increased with 94±24.16 g (p<0.01). In addition weight gain of D1 group was significantly higher than that of D2 group (p<0.01). Venlafaxine therapy induced significant increase in serum triglyceride levels (140.04±55.46 mg/dL p<0.01, 83.59±52.85 mg/dL p=0.05). This metabolic effect has been shown to be more evident in case of 10mg/kg dose therapy (p=0.03). Simultaneously, serum cholesterol levels have been reduced, however this decrease proved to be significant only in case of group D2 (p=0.03). Despite of increased triglyceride values, glucose levels were significantly decreased in both treated groups (133.33±36.18mg/dL p=0.05, 118.10±51.98 mg/dL p=0.02).
Conclusions: Our results suggest that venlafaxine administrated to rats has unwished dose related metabolic effects such as significant increase in weight and hypertriglyceridemia, however serum cholesterol and plasma glucose levels appears to be decreased by this medication.