Zammit P. SSRI-induced hypoglycemia causing confusion in a nondiabetic octogenarian. Annals of Long-Term Care: Clinical Care and Aging. 2012;20(3):28-30.
Selective serotonin reuptake inhibitors (SSRIs) are a class of compounds that affect the level of serotonin in the brain. Because decreased serotonin levels have been associated with unstable mood and depression, SSRIs are commonly used to treat depression, anxiety disorders, and some personality disorders. In geriatric patients, SSRIs are frequently recommended as a first-line treatment for depression.1 Although these agents are generally well tolerated, numerous side effects have been reported, including nausea, insomnia, sedation, sexual dysfunction, weight gain, hyponatremia, apathy, anorexia, and extrapyramidal symptoms.2 SSRIs have also been documented to affect glycemic control in diabetic patients, causing episodes of hypoglycemia and hyperglycemia.3-5 This article reports a rare case of recurrent hypoglycemia following SSRI use in a nondiabetic elderly woman. One such similar case has been previously reported.6 Although hypoglycemia is a rare complication of SSRI use, especially in nondiabetic patients, these agents should be considered in the differential diagnosis of any geriatric patient taking an SSRI and presenting with hypoglycemia.
An 82-year-old woman presented to the hospital with recurrent episodes of confusion and agitation in the morning, which tended to subside in the afternoon. The patient’s medical history included hypertension, constipation, and drug-induced parkinsonism, but she was not on any antiparkinsonian medications for the past year as these had been found to be ineffective. The patient did not have a history of cognitive impairment or of type 2 diabetes mellitus. Her regular medications included bumetanide 1 mg daily, perindopril 4 mg every night, lactulose 10 mL twice daily, and lorazepam 1 mg every night for sedation. Because the patient was suspected to have depression, paroxetine 10 mg in the morning was initiated 4 days before her presentation to the hospital for confusion and agitation.
The physical examination findings were normal except for increased tone and mild muscle rigidity from the parkinsonism. Laboratory findings were normal except for a random blood glucose (RBG) level of 43.2 mg/dL (normal, 70-110 mg/dL). The patient was treated with a sugary drink and her RBG levels went up to 77.5 mg/dL. Subsequent routine blood tests found a mildly raised creatinine level of 110 µmol/L (normal, 53-106 µmol/L), with a creatinine clearance of 31.3 mL/min/1.73 m2 based on the patient’s height of 165 cm and weight of 67 kg (normal, 75-125 mL/min/1.73 m2). Her sodium and potassium levels were within normal range at 140 mEq/L (normal, 136-142 mEq/L) and 3.6 mEq/L (3.5-5.0 mEq/L), respectively. A full blood count and liver function tests were also normal. Glycated hemoglobin A1c levels were not assessed.
We decided to regularly monitor the patient’s blood glucose levels, which revealed recurrent episodes of hypoglycemia (39.6-43.2 mg/dL) in the morning. These episodes were associated with confusion following administration of paroxetine. After paroxetine was discontinued, her episodes of confusion resolved and her glucose levels normalized, reaching levels >70 mg/dL.
Antidepressants, including SSRIs and tricyclic antidepressants, have been found to interfere with blood glucose metabolism, increasing the risk of hypoglycemic episodes.7 Several reports have implicated antidepressants, especially SSRIs, in the development of clinically relevant hypoglycemia in diabetic patients.3-5 SSRI-induced hypoglycemia in nondiabetic individuals is more rare, with only one case previously reported in the literature.6 In this previous case, the implicated medication was sertraline. Like our patient with paroxetine-induced hypoglycemia, the patient was also a woman in her eighth decade of life, but her hypoglycemia presented as presyncopal episodes approximately 25 days after sertraline was initiated as a treatment for mild depression.
Hypoglycemia can be caused by various factors, including regulatory, enzymatic, or substrate defects.7 In patients with diabetes mellitus, iatrogenic hypoglycemia can be caused by absolute or relative insulin excess and compromised glucose counterregulation, with the majority of cases involving an interplay of these factors.3 Insulin excess occurs when endogenous glucose production is decreased (eg, after consuming alcohol), use of insulin is increased (eg, during exercise), exogenous glucose delivery is decreased (eg, after a meal has been missed), sensitivity to exogenous insulin is increased (eg, during treatment with an insulin sensitizer, such as metformin or thiazolidinediones), exogenous insulin is taken inappropriately (eg, wrong dose, timing, or type), or insulin clearance is decreased (eg, as occurs with renal impairment).8 SSRIs have been shown to increase insulin sensitivity in both nondiabetic and diabetic individuals.8-12 Glucose counterregulation is a physiologic response that occurs to guard the body against hypoglycemia when plasma glucose concentration decreases.13 Through this mechanism, counterregulatory hormones, including glucagon and epinephrine, are released in an effort to rapidly restore euglycemia.8 SSRIs may cause hypoglycemia by impairing the central mechanisms that mediate hypoglycemia-induced hormonal counterregulatory responses.14 In cases of compromised glucose counterregulation, warning signals of hypoglycemia may be attenuated, leading to hypoglycemic unawareness.
SSRIs may cause hypoglycemic unawareness secondary to autonomic dysfunction. This can be an atypical manifestation of serotonin syndrome (also known as “serotonin reuptake syndrome”), a potentially life-threatening drug reaction that causes the body to retain too much serotonin.15
Patients with SSRI-induced hypoglycemia may present with any number of symptoms associated with hypoglycemia, depending on how low their blood glucose levels have dropped (Table). Because symptoms of hypoglycemia are nonspecific, patients or staff may not readily recognize them as stemming from hypoglycemia. A diagnosis is made based on clinical suspicion and documentation of low plasma or blood glucose levels, and it is confirmed when the patient’s symptoms resolve once euglycemia is attained. In the case of SSRI-induced hypoglycemia, the SSRI as the cause of the hypoglycemia becomes clear if the hypoglycemic episodes stop once the SSRI is discontinued.
Management of SSRI-induced hypoglycemia involves acute treatment to raise blood glucose levels, such as by administering oral glucose, a carbohydrate (eg, juice, crackers, soft drink), intravenous dextrose, or intramuscular glucagon, and withdrawal of the implicating medication. In patients with diabetes, reduction of hypoglycemic agents can also be considered, as this may be sufficient to stop the hypoglycemic episodes and avoid SSRI withdrawal. Because patients with diabetes are more prone to developing SSRI-induced hypoglycemia than nondiabetic individuals, it is recommended that their blood glucose levels be carefully monitored when SSRIs are initiated or discontinued.4,16
SSRIs are a commonly prescribed therapy for depression and anxiety, including in diabetic and nondiabetic elders. Although treatment with SSRIs is generally well tolerated, these agents can cause hypoglycemia in rare cases. Diabetic patients have a higher risk of experiencing SSRI-induced hypoglycemia, but as our case and another6 in the literature demonstrate, nondiabetic patients can also experience this side effect. Therefore, SSRIs should be ruled out as a possible cause of hypoglycemia in both diabetic and nondiabetic individuals presenting with recurrent episodes of hypoglycemia. Low blood glucose levels that normalize with acute treatment and cessation of hypoglycemic episodes upon discontinuation of the SSRI confirm a diagnosis of SSRI-induced hypoglycemia.
The author reports no relevant financial relationships.
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