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Positional Asphyxiation From Paroxetine

To the Editor: Paroxetine is a selective serotonin reuptake inhibitor with a unique structure and metabolic characteristics that is used in a variety of psychiatric conditions. Here we report a case of mechanical asphyxiation, suspected secondary to increased blood levels of paroxetine, in a patient taking a low dose of the medication.

Mr. A was a 19-year-old white man with a diagnosis of social phobia and major depression. He was given paroxetine, 10 mg/day, after a suicidal gesture led to a brief hospitalization. Blood work showed a bilirubin level of 1.9 mg/dl, with an upper normal level of 1.2 mg/dl; the rest of the results were within normal limits. His paroxetine dose was later increased to 20 mg/day; this was his only medication. Mr. A showed considerable improvement in his depressive symptoms and some improvement of his anxiety over the next few weeks. After forgetting to take his medication one night, he took it the next morning and took his scheduled dose later in the evening. His mother found him unresponsive on the couch the next morning.

Mr. A was pronounced dead at the scene. An autopsy reported the cause of death to be mechanical/positional asphyxiation probably secondary to paroxetine. A postmortem blood analysis showed paroxetine levels of 400 ng/ml, with caffeine and theobromine as incidental findings. No other drugs of abuse were found. A pill count did not reveal missing medication. His parents reported him to be fairly stable psychiatrically with no suicidal thoughts or intents before his death. In fact, they had noticed that he was doing better than they had seen him for some time. He had seen his psychologist 2 days before and was doing well at that appointment.

Paroxetine is generally dosed at 20–50 mg/day in single doses. Blood levels corresponding to a dose of 20 mg/day are 23–75 ng/ml. A 50-mg dose can produce blood levels as high as 207 ng/ml. The blood levels of our patient were about 10 times higher than the expected mean at that dose. Paroxetine is metabolized by the cytochrome P450 2D6 system, and the drug itself is an inhibitor of the enzyme. This results in a nonlinear metabolism, with higher doses causing a noncorresponding increase in the blood levels of the drug. Also, almost 7%–10% (1) of the white population has diminished 2D6 activity and consequently relies on unknown mechanisms for the metabolization of the drug. Dosing is guided by the clinical response; most patients improve in this dose range, and drug levels are rarely drawn.

Since toxic concentrations fail to produce reliable clinical signs, drug monitoring may be indicated. More research is needed to elucidate the relevance of slow metabolism and its adverse effects.

Reference

1. Raimundo S, Toscano C, Klein K, Fischer J, Griese EU, Eichelbaum M, Schwab M, Zanger UM: A novel intronic mutation, 2988G>A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects. Clin Pharmacol Ther 2004; 76:128–138[CrossRef][Medline]

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