Vilazodone-Induced Hyperglycemia: A Case Series.

Sir,

Studies have suggested a correlation between depression and blood glucose dysregulation.[1, 2] This could not only be because of change in insulin activity but also because of low motivation for physical activity, sedentary lifestyle, increased calorie intake, and certain medications. Vilazodone is a newer antidepressant with a novel mechanism of action. It increases adrenaline by stimulation of 5-HT receptors.[3, 4] Adrenaline increases blood glucose by various mechanisms, such as inhibition of insulin release, stimulation of glucagon, glycogenolysis, and gluconeogenesis. There has been only one case report in the past in which blood sugar levels were raised due to vilazodone. Here, we present two cases in which blood sugar levels were found to be raised after starting Vilazodone.

Case Reports

The first case is of a 45-year-old male who presented with symptoms of persistent low mood, decreased interest in routine activities, ideas of worthlessness, lethargy, and erectile dysfunction for four months. The patient had comorbid Type 2 diabetes mellitus (DM) diagnosed three years ago. He was maintained on Tab. glimepiride 2 mg and Tab. metformin 500 mg. The patient’s baseline fasting plasma sugar (FPS) was 92 mg/dL and the postprandial plasma sugar (PPPS) was 120 mg/dL, and hemoglobin A1c (HbA1c) was 6.4%. Using the International Classification of Diseases, 10th Revision (ICD-10) diagnostic criteria, a diagnosis of moderate depressive episode with somatic syndrome was considered and he was prescribed Tab. vilazodone 20 mg/day with food. After ten days, his FPS was found to be 150 mg/dL and PPPS was 232 mg/dL. As there was a temporal relation between starting vilazodone and raised sugar levels, vilazodone was stopped. Subsequently, plasma sugar was found to return to normal limits. After ten days, Vilazodone 10 mg/day was restarted, and his sugar levels were again found to be increased. Considering the increase in plasma sugar level for the second time, vilazodone was stopped, and his plasma sugar again returned to normal levels. During this period, the patient was on his usual diabetic diet and oral hypoglycemic medications. The score on the Naranjo adverse drug reaction (ADR) scale was found to be 7, suggestive of a probable ADR. The time trend between vilazodone intake and glycemic levels is shown in .

FPS: fasting plasma sugar, PPPS: postprandial plasma sugar.

The second case is of a 42-year-old male who presented with symptoms of low mood, lethargy, decreased interaction with family members, decreased libido, and loss of appetite for one month. There was no history of psychosis, bipolar affective disorder, or substance use. There was no history of comorbid medical conditions or the use of any adjunctive medications. Using the ICD-10, a diagnosis of moderate depressive episode without somatic syndrome was considered, and he was given Tab. vilazodone 20 mg once daily with food. Before initiating the treatment, his complete blood count, liver function test, renal function test, and thyroid profile were within the normal range. His FPS was 89 mg/dL, PPPS was 114 mg/dL, and HbA1c was 5.9%. The dose of vilazodone was increased to 40 mg/day, one week later. Thereafter, on follow-up after three weeks of initiation of vilazodone, his FPS was found to be 144 mg/dL, and PPPS was 210 mg/dL. As there was a temporal relation between starting vilazodone and increased plasma sugar levels, vilazodone was stopped. After five days of stopping vilazodone, his FPS was found to be reduced to 86 mg/dL and PPPS to 120 mg/dL. During this period, there was no change in his lifestyle, and the patient was on his usual diet. The score on the Naranjo ADR scale was found to be 6, suggestive of a probable ADR.

Discussion

Vilazodone is an indolalkylamine that acts as both a potent selective serotonin reuptake inhibitor (SSRI) and a 5-HT1A receptor partial agonist with a minimal capability of inhibiting norepinephrine and dopamine reuptake.

It has been demonstrated that central 5-HTlA receptor agonists, such as tetralin and buspirone, which are partial 5-HT1A receptor agonists, induce hyperglycemia in rats. 5-HT1A agonism has been known to increase plasma adrenaline levels. Adrenaline, being an inhibitor of insulin release, could potentially increase plasma sugar levels. Thus, these centrally located 5-HT1A receptors are involved in the glucose homeostasis via the activation of adrenaline release. Hyperglycemia associated with vilazodone in these cases might be related to its agonistic effect on 5-HT1A receptors, but the findings need replication.

Vilazodone is mainly metabolized by CYP3A4, with a minor contribution from CYP2C19 and CYP2D6. Metformin is not metabolized and is cleared from the body by tubular secretion and excreted unchanged in the urine, and glimepiride is biotransformed by CYP2C9. Thus, neither of the co-administered drugs (glimepiride and metformin), in case 1, have any significant pharmacokinetic or pharmacodynamic interactions with vilazodone. Though DM was a potential confounding factor in the first case, there was no confounding factor in the second case. It is therefore suggested that there is an involvement of this drug in increasing plasma sugar level.

There is a need to have more studies to find out whether vilazodone-induced hyperglycemia is dose-dependent or idiosyncratic and also to examine the complex relationship and mediational pathways between vilazodone and insulin release. Close monitoring of patients on vilazodone for blood sugar levels is therefore warranted.