Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

Abstract

Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocininduced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

Plasma insulin levels are increased by sertraline in rats under oral glucose overload

“…The administration of sertraline reduces glycemia in fasting diabetic mice (14) and decreases fasting and glucose overload glycemia in diabetic and non-diabetic rats (12). However, in the present study, insulinemia was increased by sertraline treatment only after glucose overload.…”

“…However, in the present study, insulinemia was increased by sertraline treatment only after glucose overload. In fact, in fasting diabetic mice, sertraline also does not change plasma insulin concentrations (12). Thus, it is possible that sertraline presents this interesting hypoglycemia reducing effect by more than one mechanism.…”

“…More recent clinical studies have indicated that selective serotonin reuptake inhibitors (SSRI) are better antidepressants for diabetic patients because they interfere less with plasma glucose control (9,10). Preclinical trials have shown that some SSRI reduce plasma glucose levels (11,12). In fact, sertraline has been shown to decrease fasting and overload glycemia in diabetic and non-diabetic rats (12).…”

“…Preclinical trials have shown that some SSRI reduce plasma glucose levels (11,12). In fact, sertraline has been shown to decrease fasting and overload glycemia in diabetic and non-diabetic rats (12). On the other hand, within the group of SSRI, sertraline may be the best agent for treatment of depression in diabetic patients (10).…”

“…In both groups, 10 rats received 1 ml/kg saline and the other 10 rats were injected with 30 mg/kg sertraline, a dose that decreased blood glucose levels in a previous study (12). The rats from the fasting groups were sacrificed by decapitation after 30 min, and blood was collected from the body trunk.…”