Loss of Awareness of Hypoglycemia Temporally Associated With Selective Serotonin Reuptake Inhibitors

This Caucasian female was diagnosed with type 1 diabetes at 10 years of age. She was treated with an intensive subcutaneous insulin program (total 1.1 units · kg⁻¹ · day⁻¹) and a 1,600-kcal diabetic diet. Her HbA_1c was 9.7%. Blood glucose levels <70 mg/dl occurred approximately once per week and were always accompanied by warning symptoms (hunger, diaphoresis, and generalized weakness). All low blood-glucose levels were self-treated, and there was no history of sustained hypoglycemia.

At 17 years of age, the patient became depressed and was treated with sertraline hydrochloride (200 mg orally daily). While on therapy with sertraline, she experienced decreased awareness of hypoglycemia; hypoglycemic episodes increased in frequency to two to three times per week. She had two episodes of severe hypoglycemia complicated by unconsciousness. Insulin dosages, prescribed diet, weight, and HbA_1c were similar before and during treatment with sertraline. Sertraline was discontinued 6 months later, and awareness of hypoglycemia returned.

Our second patient, a Caucasian female with cystic fibrosis, had diabetes since 14 years of age, when she presented with diabetic ketoacidosis. During treatment with an intensive subcutaneous insulin program (total 0.77 units · kg⁻¹ · day⁻¹) and a 2,300-kcal diabetic diet, HbA_1c was 8.1%. Blood glucose levels <70 mg/dl occurred three to four times per week and were typically accompanied by warning symptoms. The patient had two severe hypoglycemic episodes (manifested by lack of consciousness) over a periodof 5 years.

At 21 years of age, she became depressed and was treated with paroxetine hydrochloride (30 mg once daily). During 3 months of paroxetine treatment, she experienced sedation, fatigue, and decreased awareness of hypoglycemia. Severity of hypoglycemic episodes worsened (external assistance was required five times), as the frequency of hypoglycemia increased to four to five hypoglycemic episodes per week. Insulin dosage was decreased to a total of 0.6 units · kg⁻¹ · day⁻¹, and the prescribed meal plan remained unchanged. Her weight increased by 10 kg. The HbA_1c was 7.9%. After discontinuation of paroxetine, awareness of hypoglycemia improved dramatically; no severe hypoglycemic reactions recurred.

The mechanism of hypoglycemic unawareness in our patients is unknown. SSRIs do not influence plasma insulin levels (2) or augment hypoglycemic action of injected insulin (3). SSRIs do not seem to affect ACTH, cortisol, growth hormone (4), or sympatho-adrenal responses to insulin-induced hypoglycemia (5). SSRI-associated hypoglycemic unawareness may result from autonomic dysfunction, comprising a forme fruste of serotonin syndrome. A similar mechanism may cause some anorgasmia in SSRI-treated patients.

In conclusion, SSRIs are effective antidepressants commonly used in patients with diabetes. However, we advise close monitoring for potential loss of hypoglycemic awareness in diabetic patients treated with SSRIs.