Fatality Related to a 30-g Venlafaxine Overdose
Fatality Related to a 30-g Venlafaxine Overdose
A 30-g venlafaxine overdose resulted in death for a 39-year-old woman whose 43-day clinical course was highlighted by refractory hypotension and the resulting complications of bowel ischemia and perforation. Her venlafaxine and O-desmethylvenlafaxine levels, analyzed by high-performance liquid chromatography one day after ingestion, were 21.82 mg/L (therapeutic range 0.1-0.5 mg/L) and 3.33 mg/L (0.2-0.4 mg/L), respectively. These levels remained elevated for over 7 days. Postulated explanations for these extended elevated levels were saturation of drug metabolism, decreased drug metabolism, and existence of a genetic polymorphism. Our patient's venlafaxine overdose produced a wide variety of clinical challenges, to include seizures, tachycardia, decreased level of consciousness, refractory hypotension, and bowel dysmotility. In addition, this case augments the growing body of literature that suggests that venlafaxine may be fatal in overdose situations.
Venlafaxine is a nontricyclic antidepressant derived from phenethylamine. It is structurally unrelated to other antidepressants and has an active metabolite, O-desmethylvenlafaxine. Both the parent drug and its metabolite are potent inhibitors of neuronal serotonin and norepinephrine reuptake at the postsynaptic membrane and are weak inhibitors of dopamine reuptake. Second-generation antidepressants, such as venlafaxine, have several proposed advantages: they are effective in treating depression, have a favorable side-effect profile, and are considered as safe in an overdose situation as the selective serotonin reuptake inhibitors (SSRIs).
Careful perusal of mirtazapine, bupropion, and nefazodone use substantiates the claim that these newer antidepressants have a wide therapeutic index in overdose situations. A recent case report of a patient who ingested 30 times the normal daily dose of mirtazapine in a suicide attempt reported no adverse sequelae. Bupropion has associated toxicities, such as central nervous system effects (seizures), but rarely, cardiotoxicities, whereas nefazodone demonstrated a low toxicity profile in overdose situations in an analysis of 1338 exposures. However, venlafaxine overdose has been associated with excess adrenergic stimulation, seizures, arrhythmias, bradycardia, hypertension, hypotension, and death. A recent observational study from a United Kingdom registry of fatal toxicities in relation to number of prescriptions filled showed that venlafaxine has toxicities higher than those of other serotonergic drugs (13.2 deaths/million prescriptions, 95% confidence interval [CI] 9.2-18.5), but similar to those of tricyclic antidepressants.
A 30-g venlafaxine overdose resulted in death for a 39-year-old woman whose 43-day clinical course was highlighted by refractory hypotension and the resulting complications of bowel ischemia and perforation. Her venlafaxine and O-desmethylvenlafaxine levels, analyzed by high-performance liquid chromatography one day after ingestion, were 21.82 mg/L (therapeutic range 0.1-0.5 mg/L) and 3.33 mg/L (0.2-0.4 mg/L), respectively. These levels remained elevated for over 7 days. Postulated explanations for these extended elevated levels were saturation of drug metabolism, decreased drug metabolism, and existence of a genetic polymorphism. Our patient's venlafaxine overdose produced a wide variety of clinical challenges, to include seizures, tachycardia, decreased level of consciousness, refractory hypotension, and bowel dysmotility. In addition, this case augments the growing body of literature that suggests that venlafaxine may be fatal in overdose situations.
Venlafaxine is a nontricyclic antidepressant derived from phenethylamine. It is structurally unrelated to other antidepressants and has an active metabolite, O-desmethylvenlafaxine. Both the parent drug and its metabolite are potent inhibitors of neuronal serotonin and norepinephrine reuptake at the postsynaptic membrane and are weak inhibitors of dopamine reuptake. Second-generation antidepressants, such as venlafaxine, have several proposed advantages: they are effective in treating depression, have a favorable side-effect profile, and are considered as safe in an overdose situation as the selective serotonin reuptake inhibitors (SSRIs).
Careful perusal of mirtazapine, bupropion, and nefazodone use substantiates the claim that these newer antidepressants have a wide therapeutic index in overdose situations. A recent case report of a patient who ingested 30 times the normal daily dose of mirtazapine in a suicide attempt reported no adverse sequelae. Bupropion has associated toxicities, such as central nervous system effects (seizures), but rarely, cardiotoxicities, whereas nefazodone demonstrated a low toxicity profile in overdose situations in an analysis of 1338 exposures. However, venlafaxine overdose has been associated with excess adrenergic stimulation, seizures, arrhythmias, bradycardia, hypertension, hypotension, and death. A recent observational study from a United Kingdom registry of fatal toxicities in relation to number of prescriptions filled showed that venlafaxine has toxicities higher than those of other serotonergic drugs (13.2 deaths/million prescriptions, 95% confidence interval [CI] 9.2-18.5), but similar to those of tricyclic antidepressants.
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