Discussion
We report the case of a multiple drug overdose involving
Nortriptyline, Livergol,
Gabapentin, and Thiamine supplement, which resulted in a QTc interval
prolongation presented on ECG on arrival. According to the 2020 Annual
Report of the American Association of Poison Control Centers’ National
Poison Data System, antidepressants are reported among the top 5
substance classes most frequently involved in toxic exposures, and over
the past 10 years, their exposure has increased most rapidly and with
more serious outcomes, by 5.84% per year or 1,793 cases per year
[5]. As a class, TCAs are categorized in the top 25 classes
associated with the greatest fatality [6].
Delayed clinical deterioration or even death following a relative
stabilization or improvement, days after the ingestion had been
previously documented. A previous case, reports a 61-year-old man
presenting after an nortriptyline overdose up to 2500 mg, with QRS
widening to 240 milliseconds despite the further narrowing of QRS
interval, his course got complicated by repeated episodes of wide
complex tachycardia and required continuous sodium bicarbonate treatment
until day 14 hospitalization [7]. In another case of a patient with
an initial nortriptyline level of 1518 mg/L and episodes of generalized
tonic-clonic seizures, sodium bicarbonate infusion was administrated for
a total of 5 days [8]. however, in all of these cases, significant
initial toxicity was observed. Our patient with large ingestion of
Nortriptyline still showed no delayed deterioration and responded very
well on a short (12 hours) sodium bicarbonate treatment course. In line
with the result of our case, in a report by Pierog and colleagues,
despite a large amount of amitriptyline ingested, the patient only
received therapy for 48 hours [9].
The recommended therapeutic window of NT is defined between 50 ng/mL and
150 ng/mL. Normally, medications
with NT start at a low dose, and then gradually increased to reach the
optimal therapeutic level. However, the plasma steady-state
concentrations of TCAs in the course of treatment vary interindividual,
as the therapeutic or toxic concentrations are mostly determined by NT
metabolism and clearance rate. But, in general, plasma levels above 150
ng/mL are associated with the incidence of adverse effects [10].
Given that, conventional dosage regimen can lead to toxic concentration
in slow metabolizer individuals, as Lee et al. reported a case
presenting with adverse effects such as dizziness, dry mouth, and
constipation after 6 days prescription of routine dosage of NT [11].
Drug interactions leading to the decreased metabolism rate can be
observed in treatment with two or more CYP enzyme metabolizers,
resulting in enzyme competition. Shim et al. reported increased blood
levels of TCA in schizophrenic patients under treatment of paroxetine, a
potent CYP2D6 inhibitor [12].
Several successful studies have been evaluating silymarin’s benefits as
an anti-inflammatory, anti-diabetic, anti-Alzheimer, and anticancer
agent. Due to the extensive therapeutic roles of Livergol in human
studies and its wide use in liver diseases, its safety is very important
and should be prescribed with caution, especially when co-administered
with drugs that carry a narrow therapeutic window. According to
pharmacological studies, silymarin was safe at therapeutic doses in
humans, only transient side effects like GI discomfort were reported.
Silymarin has shown limited effect on the pharmacokinetics of some drugs
in vivo; inhibitory effect on cytochrome P-450 enzymes could affect
warfarin metabolism. Though it did not have a major effect on drug
metabolism, it is suggested that their combination should be used with
caution. In total, Livergol has a good safety profile and is well
tolerated even at high doses [3, 13].
One major cause of concern in the use of herbal medicine is that they
mainly contain physiochemical constituents that may interact with
prescription drugs. Regarding the little information available about
herbal product potential for drug interaction and pharmacokinetic
alternation, healthcare practitioners usually take caution against
co-administration of Livergol and pharmaceutical drugs to avoid any
possible clinically significant interactions [14].