sindrome serotoninergica em gatos, PUGH 2010

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Retrospective Study Journal of Veterinary Emergency and Critical Care 23(5) 2013, pp 565–570
doi: 10.1111/vec.12091
Selective serotonin reuptake inhibitor (SSRI)
toxicosis in cats: 33 cases (2004–2010)
Cassandra M. Pugh, DVM; Joseph T. Sweeney; Christopher P. Bloch, PhD; Justine A. Lee, DVM,
DACVECC, DABT; Justine A. Johnson, DVM, DACVECC and Lynn R. Hovda, RPH, DVM, MS,
DACVIM
Abstract
Objective – To evaluate a population of cats with selective-serotonin reuptake inhibitor (SSRI) toxicosis and
characterize the population affected, list products ingested, the clinical signs observed, treatments performed,
length of hospitalization, patient outcome, and overall prognosis.
Design – Retrospective study from 2004 to 2010.
Setting – Referral veterinary center.
Animals – Thirty-three witnessed cat SSRI ingestions.
Interventions – None.
Measurements and Main Results – The medical records of cats with a witnessed SSRI ingestion identified by
review of an animal poison control center electronic database were evaluated. The most common SSRIs ingested
were venlafaxine (Effexor; 12/33; 36%), fluoxetine (Prozac; 12/33; 36%), citalopram (Celexa; 6/33; 18%), and
escitalopram (Lexapro; 3/33; 9%). Overall, 24% of cats (8/33) became symptomatic, while 76% (25/33) remained
asymptomatic. Of the symptomatic cats, sedation was the most common clinical sign (6/8; 75%), followed by
gastrointestinal signs (4/8; 50%), central nervous system stimulation (1/8; 13%), cardiovascular signs (1/8;
13%), and hyperthermia (1/8; 13%). Veterinary care was sought in 20 cats (20/33; 61%). Sixteen cats (16/20;
80%) were hospitalized, while 4 cats (4/20; 20%) were treated as outpatients. Treatment for hospitalized patients
included administration of IV fluid therapy (14/16; 88%), activated charcoal (12/16; 75%), anti-arrhythmic
agents (7/16; 44%), methocarbamol (6/16; 38%), cyproheptadine (6/16; 38%), anti-emetics (5/16; 31%), and
sedation (5/16; 31%). Diagnostics included blood work (7/16; 44%), blood pressure measurement (3/16; 19%),
and electrocardiogram monitoring (2/16; 13%). Mean hospitalization time for all cases of SSRI ingestion was
14.6 ± 7.8 hours (n = 16). All symptomatic cats in this study (8/8; 100%) had resolution of clinical signs and
survived to discharge.
Conclusions – The prognosis for SSRI ingestion in this population of cats was excellent. Decontamination and
supportive care for at least 12–24 hours can be considered in cats with SSRI ingestion, particularly venlafaxine
to monitor resolution of clinical signs.
(J Vet Emerg Crit Care 2013; 23(5): 565–570) doi: 10.1111/vec.12091
Keywords: feline, human medication intoxication, prescription drugs, toxicology
Introduction
Serotonin (5-hydroxytryptamine or 5-HT) is a
monoamine neurotransmitter derived from dietary L-
tryptophan and converted by tryptophan hydroxylase.1
From the Department of Emergency and Critical Care, Ocean State Veteri-
nary Specialists, 1480 South County Trail, East Greenwich, RI 02818 (Pugh,
Johnson, Sweeney); Pet Poison Helpline, 3600 American Boulevard W, Suite
700, Bloomington, MN 55431 (Lee, Hovda); and Department of Biological
Sciences, Bridgewater State University, Bridgewater, MA 02325 (Bloch).
The authors declare no conflict of interests.
Address correspondence and reprint requests to
Dr. Cassandra M. Pugh, The Hope Center for Advanced Veterinary Medicine,
140 Park Street SE, Vienna, VA 22180, USA. Email: cpugh82@gmail.com
Submitted November 1, 2011; Accepted July 30, 2013.
Abbreviations
CNS central nervous system
ECG electrocardiogram
SS serotonin sydrome
SSRI selective serotonin reuptake inhibitor
In the central nervous system (CNS), serotonin is pro-
duced at the raphe nuclei and released to activate pre-
and postsynaptic receptors of the peripheral nervous
system. The systemic effects of serotonin include vaso-
constriction, platelet aggregation, intestinal peristalsis,
and bronchoconstriction.1, 2 Serotonin also plays a key
C© Veterinary Emergency and Critical Care Society 2013 565
C. M. Pugh et al.
role in attention, pain perception, aggression, and motor
control.1 Selective serotonin reuptake inhibitors (SSRIs)
block the reuptake of serotonin in the presynapse, in-
creasing serotonin molecules at the synaptic cleft and
allowing a prolonged pharmacologic effect.3 In recent
years, SSRIs have gained favor over previously used an-
tidepressants in people as they have minimal effects on
nonserotonin neurotransmitters, and therefore have less
anticholinergic, sedative, and cardiovascular side effects
with fewer drug interactions.4
In human medicine, SSRIs are predominately used
in the treatment of anxiety, depression, and obsessive-
compulsive disorders.1–3 Side effects reported in people
include nausea, anorexia, headaches, sexual dysfunc-
tion, and insomnia.1, 5 In human beings, SSRI toxicosis
can result in clinical signs of hyperreflexia, myoclonus,
seizures, coma, cardiotoxicity (eg, arrhythmias, Q-T pro-
longation), and in severe cases, death.4 A specific condi-
tion called “serotonin syndrome” (SS) has been identified
in people with excessive serotonin concentrations. It is
most commonly seen in patients taking multiple con-
current medications, and is characterized by changes
in mentation, neuromuscular abnormalities, and auto-
nomic dysfunction.5–7
In veterinary medicine, SSRIs are used for behav-
ioral modification, including the treatment of aggres-
sion and urine spraying.3 The most common SSRIs pre-
scribed in dogs and cats are fluoxetine, paroxetine, and
sertraline.4 Other less commonly recommended SSRIs
include citalopram, escitalopram, and venlafaxine. The
half-lives of fluoxetine, paroxetine, and sertraline in
dogs and cats are approximately 26, 20, and 20 hours,
respectively,2 while the half-lives of citalopram, escitalo-
pram, and venlafaxine are unknown in dogs or cats.
Therapeutic oral dosages for fluoxetine and paroxetine
reported in veterinary medicine typically range from 1–
2 mg/kg/d in dogs to 0.5–1 mg/kg/d in cats.8–10 The
use of SSRIs is extra label in cats, and fluoxetine is
the only SSRI specifically approved for canine behavior
modification.10
To the authors’ knowledge, SSRI ingestion and toxico-
sis in cats have not been well characterized in the veteri-
nary literature. Therefore, the purpose of this study was
to evaluate a population of cats with witnessed SSRI
ingestion, characterize the patient population, note the
SSRI ingested, clinical signs observed, diagnostics per-
formed, length of hospitalization, patient outcome, and
overall prognosis. Treatment was also described when
the information was available.
Material and Methods
Criteria for selection of cases
The electronic computer database of Pet Poison
Helpline,a an animal poison control center, was ret-
rospectively searched using the search terms “ven-
lafaxine,” “Effexor,”b “fluoxetine," “Prozac,”c “citalo-
pram,” “Celexa,”d “escitalopram,” “Lexapro,”e “sertra-
line,” “Zoloft,”f “paroxetine,” and “Paxil”g to identify
cats accidentally exposed to SSRIs between 2004 and
2010. Inclusion criteria were defined as those cats wit-
nessed to have ingested an SSRI. Exclusion criteria
were nonfeline species, incomplete case records includ-
ing cases where dosages, clinical signs, or treatments
could not be determined, multipet households, nonwit-
nessed ingestion, or cases where multiple drugs may
have been consumed. General organ system categories of
clinical signs were used to characterize the data, includ-
ing CNS depression (eg, sedation, lethargy, mydriasis,
ataxia); CNS stimulation (eg, agitation or anxiousness,
vocalization, hyperreflexia, tremors, seizures), gastroin-
testinal signs (eg, vomiting, diarrhea, nausea, drooling),
cardiovascular signs (eg, tachycardia, bradycardia, hy-
pertension), and hyperthemia.
Procedures
Data were collected via a commercially available spread-
sheet programh utilized by a poison control helpline,a
along with follow-up questionnaires distributed to the
involved owners and veterinarians. Datacollected in-
cluded signalment (including sex, age, breed, and body
weight), active ingredient of the SSRI, clinical signs, dose
ingested, treatments performed, diagnostic tests, nature
of hospitalization (characterized as either inpatient or
outpatient care), length of hospitalization when applica-
ble, and outcome. Additional follow-up with pet owners
or hospital staff was obtained by phone call when nec-
essary to complete poison control helpline case records.
All pet owners or veterinary clinics were contacted at
least 3 times for follow-up before the case was con-
sidered closed. For patients that did not receive vet-
erinary treatment, follow-up information was obtained
via phone conversation with the owner to verify out-
come. Cases that were seen by a veterinarian (regard-
less of inpatient or outpatient care) had follow-up with
both the owner and veterinarian to confirm outcome. Pa-
tients were considered survivors if they survived to dis-
charge from the hospital, or if confirmation of survival
(based on follow-up) was obtained from the pet owner or
veterinarian.
Statistical methods
Binary logistic regression was used to test whether the
development of clinical signs was associated with sex,
age, or weight of the patient, or dosage ingested. To
test for differences among drugs in mean dosage in-
gested, a single-factor analysis of variance (ANOVA) was
used, followed by Tukey’s HSD test (a post hoc multiple
566 C© Veterinary Emergency and Critical Care Society 2013, doi: 10.1111/vec.12091
Selective serotonin reuptake inhibitor toxicosis in cats
comparison test) to identify which drugs were ingested
in significantly different quantities. Spearman’s rank cor-
relation coefficient was used to test for an association
between dosages ingested (mg/kg) and clinical signs.
Unlike standard parametric correlations, this analysis
detects monotonic relationships between variables re-
gardless of whether these relationships are strictly lin-
ear. Fisher’s exact test was used to test for an association
between the development of clinical signs and the prob-
ability of hospitalization. For each analysis, a result was
considered significant if P <0.05, using a commercially
available computer program.i
Results
Of the 33 cats included in the final analysis, 20 (61%)
were male and 13 (39%) were female, with no signifi-
cant difference between symptomatic and asymptomatic
patients (P = 0.52). The mean age was 5.5 ± 5.0 years
and there was no significant difference between symp-
tomatic and asymptomatic patients (P = 0.58). The most
commonly affected breed was the domestic shorthair,
27/33 (82%), followed by the domestic long hair, 3/33
(9%), Himalayan, 1/33 (3%), Birman, 1/33 (3%), and
Siamese, 1/33 (3%). The mean weight was 4.7 ± 2.0 kg;
there was no significant difference in mean weight
between symptomatic and asymptomatic patients
(P = 0.85). There was no significant difference in mean
dosage between symptomatic and asymptomatic pa-
tients (P = 0.87). The most common SSRIs ingested
were venlafaxine (Effexor)b (12/33; 36%) and fluoxetine
(Prozac)c (12/33; 36%), followed by citalopram (Celexa)d
(6/33; 18%) and escitalopram (Lexapro)e (3/33; 9%). All
cats were exposed through accidental ingestion of a med-
ication intended for human use and not by one pre-
scribed for a specific animal.
Only 24% (8/33) cats were symptomatic at the time
of the initial phone call to an animal poison control,
while 76% (25/33) were initially asymptomatic and re-
mained the same way. Of the 8 cats exhibiting clinical
signs, sedation (6/8; 75%) was the most common clinical
sign observed in this study. Gastrointestinal signs (eg,
vomiting, diarrhea, nausea, drooling) were seen in 50%
of cats (4/8), while CNS stimulation (eg, agitation,
tremors, seizures), cardiovascular signs (eg, tachycar-
dia, bradycardia, hypertension), and hyperthermia were
each observed in 1 patient (1/8; 13%).
In this study, veterinary care was sought in 20/33
(61%) of the cases. Sixteen of 20 cats (80%) were ad-
mitted for inpatient hospitalization, while 4 cats (4/20;
20%) were treated on an outpatient basis. The over-
all mean hospitalization time, including inpatient and
outpatient time, was 14.6 ± 7.8 hours (n = 16); no
cat was hospitalized for more than 24 hours. Of the
16 cats that were hospitalized, 5 (31%) displayed clin-
ical signs. The presence of clinical signs was not asso-
ciated with whether the cats were hospitalized or not
(P = 0.44). The most common treatment for hospitalized
cats was IV fluids (14/16; 88%), followed by activated
charcoal (12/16; 75%). Anti-arrhythmic agents such as
beta blockers and anticholinergics were administered in
44% (7/16) of cases, along with methocarbamol (6/16;
38%) and cyproheptadine (6/16; 38%). Of the hospital-
ized cats, 31% received anti-emetics (5/16) and seda-
tives (5/16; 31%). Only 5/16 cats had emesis induction
performed. Blood work (7/16; 44%), blood pressure
(3/16; 19%), and electrocardiogram (ECG) monitor-
ing (2/16; 13%) were performed. Complete follow-up
information from pet owners and veterinarians was
available for 16/33 (48%) cats. All of the hospitalized
cats survived to discharge and had complete resolu-
tion of clinical signs. No deaths were reported in this
study.
Venlafaxine
Twelve cats (12/33; 36%) ingested venlafaxine. Nine
(9/12; 75%) were male and 3 (3/12; 25%) were female.
Age ranged from <1 to 12 years. The majority of cats were
domestic shorthairs (9/12; 75%) and one each (8%) of do-
mestic longhair, Himalayan, and Birman cats. The mean
weight for cats that ingested venlafaxine was 4.6 ± 1.4 kg
and the mean dose ingested was 17.4 ± 12.5 mg/kg. Six
of the 12 cats (50%) that ingested venlafaxine developed
clinical signs, with some cats developing >1 clinical sign.
Of the 6 individuals, 5 (5/6; 83%) displayed CNS de-
pression, 3 (3/6; 50%) showed CNS stimulation, 3 (3/6;
50%) displayed gastrointestinal signs, and 1 (1/6; 17%)
showed cardiovascular signs (eg, tachycardia with con-
comittant hypertension). Two (2/6; 33%) cats displayed
both CNS depression and CNS stimulation at different
times. In 4 cases (4/6; 67%), signs associated with SSRI
toxicosis involved >1 organ system. All cats exhibiting
gastrointestinal signs after venlafaxine ingestion also ex-
hibited sedation as a clinical sign (3/3). One of the symp-
tomatic cats was being treated with prednisolone at the
time of SSRI ingestion (1/6).
Eleven of the 12 (92%) cats that ingested venlafaxine
were hospitalized. The single nonhospitalized individ-
ual showed signs of sedation but was not treated. This
cat ingested the second lowest dosage of venlafaxine
(4.6 mg/kg) reported in the study. Two individuals were
treated with activated charcoal alone, while the remain-
ing 9 cats received a combination of treatments including
IV fluids (9/11; 82%) and activated charcoal (8/11; 73%)
as the most common therapies performed.
C© Veterinary Emergency and Critical Care Society 2013, doi: 10.1111/vec.12091 567
C. M. Pugh et al.
Fluoxetine
Twelve cats (12/33; 36%) ingested fluoxetine. Eight were
male (8/12; 66%) and 4 (4/12; 33%) were female. Age
ranged from <1 to 12 years old. Nine cats (9/12; 75%)
were domestic shorthairs, 2 were domestic longhairs
(2/12; 17%), and 1 was a Siamese cat (1/12; 8%). Mean
weight was 5.0 ± 2.2 kg and the mean dose ingested
was 3.5 ± 1.8 mg/kg. Of the cats ingesting fluoxetine,
2 individuals (2/12; 17%) developed clinical signs. The
first symptomatic cat, which displayed CNS stimula-
tion (eg, hyperactivity and agitation) and hyperthermia,
ingested the largest dosage (6.3 mg/kg). This individ-
ual was treated with activated charcoal and released
without hospitalization. Incidentally, this symptomatic
cat was also being treated with cyproheptadine at the
time of SSRI ingestion. The second symptomatic cat
(3.7 mg/kg) displayed both CNS depression and gas-
trointestinal signs, but was not evaluated by a veterinar-
ian and did not receive treatment.
Three cats (3/12; 25%) ingested moderatelylarge
doses (4.4–4.7 mg/kg) compared to the mean ingested
dose and were hospitalized. Each of these individuals
received a combination of treatments that included IV
fluids and activated charcoal. None of them developed
clinical signs. Emesis induction was performed in 1 cat.
Another asymptomatic individual was treated as an out-
patient and received an anti-emetic.
Citalopram
Six cats (6/33; 18%) ingested citalopram. Two were male
(2/6; 33%) and 4 were female (4/6; 67%). The age ranged
from 1 to 16 years, and all affected cats were domestic
shorthairs. The mean weight was 4.5 ± 1.7 kg, and the
mean dose ingested was 7.3 ± 1.6 mg/kg. Two of the 6
cats were taking methimazole at the time of ingestion.
Three (3/6; 50%) cats received veterinary care. Two cats
were treated as outpatients (1 was given an anti-emetic
and the other was administered activated charcoal). One
cat was hospitalized and received a variety of treatments
including IV fluids, an anti-emetic, activated charcoal, a
sedative, and blood pressure monitoring. None of these
treated cats developed clinical signs and were considered
asymptomatic.
Escitalopram
Three domestic shorthairs ingested escitalopram (3/33;
9%). One cat (1/3; 33%) was male and 2 were female (2/3;
67%). Age ranged from <1 to 9 years. The mean weight
was 5.8 ± 4.0 kg and the mean dose ingested was 9.9 ±
6.8 mg/kg. None of the cats developed clinical signs.
Only 1 cat, the youngest at 4 months old, received vet-
erinary care. This patient was hospitalized and treated
with IV fluids, an anti-emetic, and activated charcoal.
Discussion
Selective serotonin reuptake inhibitor antidepressant in-
gestions are frequently seen in feline veterinary medicine
patients. In a recent analysis of the top 10 feline tox-
ins, venlafaxine was the most common human medica-
tion accidentally ingested by cats in 2011.a In 2008, ven-
lafaxine was among the most widely prescribed SSRI
antidepressants in the United States, second only to
escitalopram.11 Due to the growing prevalence of antide-
pressant use in the United States, veterinarians should
be aware of the increasing possibility of feline exposure
to SSRI drugs.
Among the 4 drugs noted in the present study, there
was no significant association between ingested dose
and development of clinical signs. Lack of a relation-
ship between ingested dose and development of clinical
signs may be attributed to the accuracy of the pet owner’s
estimation of the amount of SSRI ingested, a small sam-
ple size, and the differences in the pharmacokinetics and
pharmacodynamics of the individual SSRI drugs in cats.
Likewise, clinical signs may have been limited due to
owner public awareness of animal poison control cen-
ters, and more rapid decontamination and treatment by
the veterinarian.
There are a number of hypotheses to explain why
some cats developed clinical signs at very low doses
while others remained asymptomatic despite very high
ingested doses. Patients that developed clinical signs
at low doses may have had underlying metabolic dis-
eases such as kidney disease or hyperthyroidism that
could affect drug metabolism; unfortunately in this cur-
rent study, underlying metabolic disease could not be
ruled out since blood work was not performed in most
of the cats. Similarly, patients on concurrent medication
may have had altered drug metabolism or additive ef-
fects. Overall, only 4 cats (4/33) were being treated with
other medications at the time of SSRI ingestion. Of the 4
cats, only 2 cats were symptomatic. No conclusion can be
made from this small sample size of cats given that each
cat had a different combination of SSRIs and concurrent
medications.
Several cytochrome isoform enzymes are competi-
tively inhibited by or metabolize SSRIs, and have been
identified in human and veterinary medicine, which may
contribute to the lack of statistical significance between
ingested dose and clinical signs in this study. In dogs
and cats, it has been documented that certain drugs
can inhibit (eg, ketoconazole, cimetidine) or are metab-
olized by (eg, tramadol) the cytochrome P450 pathway,
thereby enhancing or prolonging SSRI toxicosis by de-
laying effective metabolism and extending SSRI effects
through enterohepatic recirculation.8, 12 Mechanisms by
which SSRI toxicosis can occur include a decrease in
568 C© Veterinary Emergency and Critical Care Society 2013, doi: 10.1111/vec.12091
Selective serotonin reuptake inhibitor toxicosis in cats
serotonin metabolism (eg, MAOIs), a decrease in sero-
tonin reuptake (eg, other SSRIs, tricyclic antidepres-
sants), an increase in serotonin precursors, or an increase
in serotonin release.13 Kalueff et al14 suggested genetics
may contribute to SS-like behavior following adminis-
tration of serotonergic drugs by genetically altered mice.
Further investigations are warranted to evaluate the cy-
tochrome P450 pathway metabolism of SSRIs in veteri-
nary patients and the effects of common concurrent med-
ications.
Selective serotonin reuptake inhibitors are generally
highly protein-bound, rapidly metabolized by the liver,
and excreted through urine.2, 3 Venlafaxine, however,
is not highly protein-bound and has a shorter half-life
in dogs (2–4 h) as compared to the other SSRIs.2
Newly reclassified as a subtype of antidepressants called
serotonin-norepinephrine reuptake inhibitors, venlafax-
ine is also functionally distinct from the other antide-
pressants in that inhibition of both serotonin and nore-
pinephrine occurs.2 Recent evidence in human medicine
suggests that there is also reuptake inhibition of
dopamine, making venlafaxine less selective for inhibi-
tion of serotonin reuptake alone.15 It is possible that vet-
erinary patients could be at higher risk to develop clini-
cal signs with venlafaxine ingestion due to the combined
effects of serotonin, norepinephrine, and dopamine re-
uptake inhibition. The mean dose of venlafaxine in-
gested was higher than that of fluoxetine, citalopram,
and escitalopram in this study and a larger proportion
of cats that ingested venlafaxine became symptomatic
compared with the other drugs. Isbister16 found that ven-
lafaxine at higher dosages in people was more likely to be
toxic than at lower doses with a higher fatality rate and
an increased risk of seizures and cardiotoxicity. Based
on the data collected in this study, however, a higher in-
gested venlafaxine dose did not increase the incidence
of clinical signs, but may prove to be more problematic
in cats compared to the other SSRI drugs.
None of the cats in this study that ingested citalopram
or escitalopram showed clinical signs. In this study, the
lowest toxic doses of venlafaxine and fluoxetine ingested
that resulted in clinical signs were 4.6 and 6.3 mg/kg, re-
spectively. However, early decontamination of patients
ingesting lower dosages may preclude the establishment
of minimum toxic dose for these drugs in cats. While the
minimum dose where clinical signs develop in cats could
not be documented in any of the 4 SSRI drugs used in
this study, the literature does show cats that have been
treated with fluoxetine at 50 mg/kg developed gastroin-
testinal and CNS signs.3 With chronic administration
>1 year of fluoxetine at 3 mg/kg/d, mild gastrointestinal
signs have been observed.3 Tremors, seizures, and brady-
cardia have also been documented at chronic doses of
5 mg/kg/d.3 Dogs that have ingested venlafaxine have
shown mild depression at doses of 1 mg/kg and tremors
noted at 10 mg/kg.2 Unfortunately given the nature of
this study, the individual toxic SSRI doses for each drug
could not be determined as signs occurred or did not
occur over a wide range of doses and successful decon-
tamination may confound the actual absorbed dose.
In this current study, the exact time of onset of clini-
cal signs was not available for 42% of the cats (14/33).
For those cats where the time of onset was known (58%;
19/33), clinical signs developed within 1 to 6 hours of
SSRI ingestion. All patients that were hospitalized withclinical signs were released within 12–24 hours of admis-
sion, suggesting that the clinical signs in cats with SSRI
toxicosis resolve within a similar time frame as com-
pared to dogs. Gwaltney-Brant et al17 evaluated 21 dogs
exposed to toxic amounts of 5-hydroxytryptophan (5-
HTP), a common over-the-counter herbal supplement
converted into 5-hydroxytryptamine (serotonin). Clini-
cal signs developed in 90.5% (19/21) of dogs and the
onset of clinical signs occurred between 10 minutes and
up to 4 hours postingestion, with the duration of clinical
signs lasting up to 36 hours.
The majority of cats in this study (61%) were evaluated
at various emergency veterinary hospitals. Regardless of
whether or not they displayed clinical signs at the time
of presentation, most evaluated cats were hospitalized
and received a variety of treatments at that time. Many
of these patients received multiple types of treatments
and diagnostics. Most cats were asymptomatic at the
time of admission and initiation of treatment or specific
treatment modalities could not be related with patient
outcome. In cats displaying clinical signs of SSRI toxico-
sis, however, symptomatic and supportive care measures
are warranted. Intravenous fluids should be used for
supportive measures in dehydrated or clinically symp-
tomatic patients; it is important to note that fluid ther-
apy will not enhance the excretion of these drugs and
is not a requirement for therapy in every case.3 Patients
not requiring IV fluids may still benefit by having an
IV catheter placed for quick venous access in the event
CNS signs (eg, tremors, seizures) develop.3 Monitoring
of blood pressure and heart rate are also warranted in af-
fected patients, as tachyarrhythmias, bradyarrhythmias,
hypertension, and hypotension may develop in SSRI tox-
icosis. The use of anti-arrhythmic medications including
beta blockers, such as propranolol, and anticholinergics,
such as atropine, can be used when indicated for tachy-
cardia or bradycardia, respectively. It is not clear why
some patients with clinical signs were not admitted yet
patients that did not display clinical signs were hos-
pitalized. Time of decontamination, owner preferences,
and financial limitations may all have been contributing
factors determining hospitalization; this information
was not available in this study.
C© Veterinary Emergency and Critical Care Society 2013, doi: 10.1111/vec.12091 569
C. M. Pugh et al.
At both therapeutic and toxic doses, SS is a common
sequela to SSRI toxicosis in human medicine. Serotonin
syndrome is a clinical diagnosis and specific criteria have
been used to identify this syndrome in human beings
(Sternbach’s criteria).5 The criteria are based on the ex-
posure to serotonergic agents in absence of other possible
etiologies (eg, infection, substance abuse) with at least 3
symptoms (eg, mentation change, agitation, myoclonus,
hyperreflexia, tremors, diarrhea, incoordination, fever)
present. In veterinary medicine, signs of SS are not
well defined; however, it is still considered a potentially
life-threatening drug reaction to excessive serotonin lev-
els. Treatment for SS is typically symptomatic and sup-
portive. The experimental use of cyproheptadine, a sero-
tonin antagonist, has been shown to block SS in animals;
however, there are no controlled clinical human or vet-
erinary trials to support its efficacy.6 No cats in this study
were noted to have met the full criteria of SS based on
human criteria. In the future, further investigation of
SS may be of benefit in veterinary medicine, adapting
specific criteria used in human medicine to establish
whether SS occurs in veterinary patients and whether
using cyproheptadine as a treatment is efficacious.
There were several limitations in this retrospective
study. First, historical accuracy of toxicology informa-
tion provided by the pet owner (eg, the exact number
of pills ingested, milligram strength) was based on the
pet owner’s estimation, which may not always be ac-
curate. As no serum SSRI blood concentrations were
measured, definitive exposure could not be confirmed.
Nevertheless, to help guide therapy, the most practical
information available is typically obtained as part of a
thorough history subsequent to initiation of the phone
call to an animal poison control center; this information
is based on drug availability, milligram size, and ver-
ification from an extensive poison database.j Different
time points in which the patient developed clinical signs
were not known for all patients, making the exact time
of onset and duration of clinical signs difficult to de-
rive. Although the small sample size in this study does
not allow for statistical significance in most analyses,
the descriptive information obtained is clinically rele-
vant to further increase awareness to owners and veteri-
narians about the potential for SSRI toxicosis. Increased
awareness will likely lead to more reported cases, from
which statistically significant information may then be
derived.
Overall, the prognosis for SSRI overdose in cats ap-
pears to be excellent. Current recommendations for treat-
ment include decontamination (eg, emesis induction,
administration of activated charcoal) when appropri-
ate to time of ingestion, heart rate, blood pressure, and
ECG monitoring, and hospitalization for supportive and
symptomatic care for 12–24 hours for patients with sus-
pected ingestion. Prospective studies evaluating the effi-
cacy of other therapies such as serotonin antagonists are
warranted to evaluate benefit to the treatment of patients
with SSRI toxicosis.
Footnotes
a Pet Poison Helpline, Minneapolis, MN.
b Effexor, Pfizer, Mission, KS.
c Prozac, Eli Lilly, Indianapolis, IN.
d Celexa, Forest Laboratories, St Louis, MO.
e Lexapro, Forest Laboratories.
f Zoloft, Pfizer.
g Paxil, GlaxoSmithKline, Middlesex, UK.
h Microsoft Excel (2003), Microsoft Corporation, Redmond, WA.
i SPSS software for Windows, 17.0.0, SPSS Incorporation, Chicago, IL.
j POISINDEX System, Version 5.1, Thomson Reuters (Healthcare), Green-
wood Village, CO.
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