Two Fatal Cases of Venlafaxine Poisoning

Abstract

Venlafaxine is a phenethylamine derivative that has recently been approved for use in the treatment of depression. It is chemically unrelated to tricyclic, tetracyclic, or other available antidepressant agents. Anticholinergic, hypotensive, hypertensive, and cardiotoxic side effects are rare. Two fatal cases encountered at separate laboratories are discussed, both involve high levels of venlafaxine. Concentrations of the drug in peripheral blood, heart blood, urine, vitreous humor, and liver are reported. Descriptions of extraction and gas chromatographic methods for confirmation and quantitation are included.

Neuropharmacology of venlafaxine

“…In addition, widening of the QRS interval has been seen in some patients [Kokan and Dart, 1996]. There have been only a few reports of death associated with venlafaxine overdose and the mechanisms underlying these fatalities are unclear [Parsons et al, 1996;Jaffe et al, 1999]. To understand the cardiovascular properties of venlafaxine, Khalifa et al [1999] examined its effects on the inward I Na current, which is the major depolarizing current involved in impulse propagation within the ventricles.…”

The redistribution of selected psychiatric drugs in post-mortem cases

“…There was also no significant difference in the result if drugs were categorized according to drug type (SSRI, SNARI and antipsychotic) or results for all drugs were tested together in one group. If results from previously published studies were also included, correlations still did not reach significance [8][9][10][11][12][13][18][19][20][21].…”

“…It was suggested that the drugs were administered in hospital and the differences in concentration between the two specimens were most likely a result of incomplete absorption. In the two studies in which post-mortem peripheral and central blood venlafaxine and metabolite concentrations were compared, central blood concentrations were approximately 1.5-2 times those found in peripheral blood [8,9,12].…”

“…Tissue distribution of several serotonin reuptake inhibitors (SSRI) and atypical antidepressants has been studied [6][7][8][9][10][11][12][13]. In many cases, only one blood sample was taken, so it was impossible to determine if redistribution had actually occurred.…”

Simultaneous separation and determination of process-related substances and degradation products of venlafaxine by reversed-phase HPLC

“…Several methods have been described to determine venlafaxine in biological fluids [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The techniques used include CE with UV and MS detection [7][8][9][10][11][12], GC [13][14][15] and HPLC with UV [16][17][18], MS/MS [19], coulometric [20], electrochemical [21] and flourimetric [22] detections. Makhija and Vavia have studied the stability of venlafaxine by HPLC [18], without characterizing the products of degradation.…”