Citalopram, escitalopram: overdoses are more serious than with other SSRIs
Selective serotonin reuptake inhibitor have congenital long QT syndrome, had
(SSRI) antidepressants are generally less
toxic in overdose than tricyclic antidepres-
sants or venlafaxine, an antidepressant
with both serotonergic and noradrenergic
activity (1,2). The symptoms observed in
cases of SSRI overdose are mainly nausea
and vomiting and serotonin syndrome, but
seizures, arrhythmia and coma also
occur(1,3). In 2006, the UK drug regulatory
agency, MHRA, reported that citalopram is
more cardiotoxic and neurotoxic than other
SSRIs(2).
In early 2016, what is known about the
harms of an overdose of citalopram or its
S-enantiomer escitalopram, compared with
other SSRIs?
This article summarises the main ind-
ings of our literature search.
Citalopram: more deaths through
overdose. In the UK, data on prescriptions
and deaths between 2000 and 2006 were
obtained from several databases to study
deaths caused by drug poisoning: citalo-
pram was implicated in about 1.1 deaths
per million prescriptions (95% conidence
interval(95CI): 0.8 to 1.4), versus 0.4 with
sertraline (95CI: 0.2 to 0.8), and 0.3 with
both luoxetine (95CI: 0.2 to 0.5) and par-
oxetine (95CI: 0.1 to 0.5)(4).
The rate was even higher with venlafax-
ine (2.5; 95CI: 2.0 to 3.1), and higher yet
with tricyclic antidepressants (13.8; 95CI:
13 to 14.7).
Seizures and arrhythmia. In 8 case
reports of fatal overdose provoked by
ingestion of citalopram alone, described in
patients aged 17 to 56 years, the dose was
known in 5cases and was between 840mg
and 3920mg. Two deaths were attributed
to arrhythmia and/or seizures. Arrhythmia
was considered a possible cause of death
in 6cases(5-7).
An Australian group examined
469patients hospitalised for an SSRI over-
dose(3). Citalopram was associated with
greater QT prolongation than the other
SSRIs.
In another similar study, seizures were
reported in 5.6% of citalopram overdoses
and 8.3% of venlafaxine overdoses(2,8).
Escitalopram: case reports of QT pro-
longation. QT prolongation (QTc of 469ms
and 521ms) was reported in two girls aged
14 years and 15 years who ingested
200mg and 500mg of escitalopramrespec-
tively (9,10). One girl, who was found to
3- Isbister GK et al. Relative toxicity of selective
several episodes of torsades de pointes serotonin reuptake inhibitors (SSRIs) in over-
dose J Toxicol Clin Toxicol 2004; 42 (3): 277-285.
(10). Our literature search did not identify 4- Hawton K et al. Toxicity of antidepressants:
any case reports of fatal overdose with rates of suicide relative to prescribing and non-
fatal overdose Br J psychiatry 2010; 196 (5): 354-
escitalopram alone. 358.
5- Ostrm M et al. Fatal overdose with citalo-
Escitalopram: studies involving hun- pram Lancet, 1996; 348: 339-340.
6- Kraai EP and Seifert SA Citalopram overdose:
dreds of overdoses. An Australian group a fatal case J Med Toxicol 2015; 11 (2): 232-236.
analysed 79 escitalopram overdoses 7- Penfornis C et al. Fatal case of citalopram
(median dose 140 mg) that occurred intoxication Vet Human Toxicol 1998; 40 (3): 178.
8- Kelly CA et al. Comparative toxicity of citalo-
between 2003 and 2008, identiied from a pram and the newer antidepressants after over-
hospital database (11). In 46cases, escit- dose J Toxicol Clin Toxicol 2004; 42 (1): 67-71.
9- Scharko AM and Schumacher J Prolonged
alopram was the only toxic drug ingested. QTc interval in a 14-year-old girl with escitalo-
No seizures were reported. Among the pram overdose J Child Adolesc Psychopharmacol
patients who had taken escitalopram alone, 2008; 18 (3): 297-298.
10- Singh P and Maldonado-Duran JM Drug-
13% had bradycardia and 9% had QT pro- induced QT prolongation as a result of an escitalo-
longation. pram overdose in a patient with previously undi-
A US study analysed 1179intentional or agnosed congenital long QT syndrome Case Rep
Med 2014: 4pages.
unintentional escitalopram-only overdoses 11- van Gorp F et al. Clinical and ECG effects of
(mean dose 212 mg) reported to Texas escitalopram overdose Ann Emerg Med 2009; 54
poison control centres between 2002 and (3): 404-408.
12- Forrester MB Escitalopram ingestions
2005. None were fatal. Five patients had reported to Texas poison control centers, 2002-
unspeciied ECG abnormalities or rhythm 2005 Hum Exp Toxicol 2007; 26 (6): 473-482.
13- Hayes BD et al. Comparison of toxicity of
disorders, and 22other patients had severe acute overdoses with citalopram and escitalo-
tachycardia (no further details provided). pram J Emerg Med 2008; 39 (1): 44-48.
Three patients had seizures(12). 14- Yilmaz Z et al. Escitalopram causes fewer
seizures in human overdose than citalopram Clin
Toxicol (Phila) 2010; 48 (3): 207-212.
Escitalopram versus citalopram com-
parisons: more seizures with citalopram.
A US team compared 421 escitalopram-
only overdoses (median dose 130mg) with
374 citalopram-only overdoses (median
dose 310mg) reported to 6poison control
centres between 2002 and 2005(13). No
statistically signiicant difference was found
between the drugs in terms of the frequen-
cy of QT prolongation or coma. No cases of
arrhythmia occurred. Seizures were more
common with citalopram than with escitalo-
pram: 8.0% versus 0.2% (p<0.001). One
case of repeated seizures was reported
after ingestion of 300 mg of escitalopram.
These results are consistent with those
of a Swiss study that compared 316citalo-
pram-only overdoses with 63 escitalo-
pram-only overdoses: QT prolongation
occurred with similar frequency with both
drugs, but seizures were more common
with citalopram (13.5%) than with escitalo-
pram (1.6%) (p=0.0065)(14).
Prescrire
Selected references from Prescrires literature
search.
1- Depression + luoxetine. In: Martindale
The Complete Drug Reference The Pharmaceu-
tical Press, London. www.medicinescomplete.
com accessed 25 February 2016: 92pages.
2- Prescrire Editorial Staff Venlafaxine: more
dangerous than most selective serotonergic
antidepressants Prescrire Int 2016; 25 (170):
96-99.
PRESCRIRE INTERNATIONAL SEPTEMBER 2016/VOLUME 25 N 174 Page 211