Antidepressants, thiazide diuretics and alcoholism: central pontine myelinolysis waiting to happen?

Abstract

A 50-year-old man, with a known weekly alcohol intake of almost 100 units, presented to his GP feeling drowsy. Routine blood tests revealed a profound hyponatraemia of 100 mmol/litre, and he was referred to hospital for investigations. On admission he was drowsy, but had a Glasgow Coma Scale score of 15, an abbreviated mental test score of 10/10 and an entirely normal neurological examination. Liver function tests were consistent with excessive alcohol consumption. He had been prescribed bendroflumethazide and clomipramine (a tricyclic antidepressant) by his GP. In view of their potential tocause hyponatraemia these were subsequently withheld and he was fluid restricted to 1.5 litres per day. His sodium level rose gradually and on day 5 of admission it had increased to 122 mmol/litre. He was discharged on day 8 having been advised to stop drinking. Less than a week after discharge he represented to his GP with symptoms of excessive sweating, shaking, constipation, disorientation and dysarthria. He was febrile at 38.6°C , and had a blood pressure of 180/90 mmHg. Electrolytes were normal (Na+ 135 mmol/litre). Although he denied consuming any alcohol since his initial admission, his symptoms were consistent with acute alcohol withdrawal and he was treated accordingly. He failed to improve on two attempts at reducing doses of chlordiazepoxide. His dysarthria progressed until his speech was difficult to understand and his swallow became unsafe. He continued to spike temperatures throughout the admission and although a catheter specimen of urine was positive for enterococcus, treatment with a prolonged course of antibiotics had not resolved his fever. A computed tomography scan of his head and a lumbar puncture were performed. Other than cortical atrophy in keeping with alcohol abuse, neither investigation provided any answers. It was considered that his symptoms could be explained by autonomic dysfunction. In view of his corrected hyponatraemia, central pontine myelinolysis was suggested and a magnetic resonance imaging head scan was performed (Figure 1). This confirmed the presence of central hyperintensity on the water sensitive sequences within the central pons, in keeping with an osmotic demyelination syndrome. Additionally these changes were identified within the caudate nuclei, possibly accounting for the patient's inability to fully control voluntary movement. The ongoing temperatures without sepsis suggested hypothalamic involvement. Following diagnosis this patient failed to improve. Treatment became supportive, and he died 7 weeks later.

Central Pontine Myelinolysis With Carbamazepine-Induced Syndrome of Inappropriate Antidiuretic Hormone and Its Management: A Case Report and Literature Review

“…Hyponatremia is a potential side effect of numerous neuropsychiatric drugs. About 10-25% of those with persistent mental illness may have primary polydipsia, which raises the risk of hyponatremia and early death [ 16 ]. Carbamazepine, serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, opioids, and polypharmacy with multiple antipsychotic drugs are the primary medication classes used daily in neuropsychiatry where hyponatremia is a side effect or reported to occur after use [ 17 ].…”

“…Carbamazepine, serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, opioids, and polypharmacy with multiple antipsychotic drugs are the primary medication classes used daily in neuropsychiatry where hyponatremia is a side effect or reported to occur after use [ 17 ]. Other frequently prescribed drugs that raise the risk of hyponatremia include salt-losing diuretics, tobacco, non-steroidal anti-inflammatory drugs, and acetaminophen [ 16 , 17 ]. A thorough clinical evaluation and understanding of fluid and electrolyte balance are necessary to decide whether to initially correct hyponatremia with normal saline or much more slowly with hypertonic 3% saline for short periods.…”

Mielinolisis central pontina con síndrome de atrapamiento asociada a hipovitaminosis

“…El uso de medicamentos neuropsiquiátricos también se ha reportado como causa de MCP, debido a que algunos de ellos causan hiponatremia. Entre estos se mencionan carbamazepina, oxcarbazepina, inhibidores selectivos de la recaptura de serotonina, litio, antidepresivos tricíclicos y algunos opiodes [17][18][19] .…”

Central Pontine Myelinolysis: A Metabolic Disorder of Myelin

“…13,21 Primary medications or classes of medications used daily in neuropsychiatry in which hyponatremia is a side effect or reported to occur after use include carbamazepine, oxcarbazepine, the serotonin reuptake inhibitors (SSRIs), lithium, tricyclic antidepressants, opioids, and polypharmacy with multiple antipsychotic drugs. 20,[22][23][24] Other classes of commonly used medications that increase risk of hyponatremia include salt-losing diuretics, nicotine, nonsteroidal anti-inflammatory drugs, and acetaminophen. 20…”