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Case Records of the Massachusetts General Hospital

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Case 9-2019: A 62-Year-Old Man with Atrial

Fibrillation, Depression, and Worsening Anxiety
Justin A. Chen, M.D., M.P.H., Leon M. Ptaszek, M.D., Ph.D.,
Christopher M. Celano, M.D., and Scott R. Beach, M.D.​​

Pr e sen tat ion of C a se

Dr. Jonathan P. Zebrowski (Psychiatry): A 62-year-old man was evaluated in the psy- From the Departments of Psychiatry
chiatry clinic of this hospital because of depression and worsening anxiety. (J.A.C., C.M.C., S.R.B.) and Medicine
(L.M.P.), Massachusetts General Hospi‑
The patient had received a diagnosis of major depressive disorder from a psy- tal, and the Departments of Psychiatry
chiatrist 15 years before this presentation, after his wife had received a diagnosis (J.A.C., C.M.C., S.R.B.) and Medicine
of cancer while she was pregnant with their daughter. The patient had severe de- (L.M.P.), Harvard Medical School —
both in Boston.
pression and the onset of generalized anxiety symptoms in association with his
wife’s progressive illness and ultimate death. Trials of buspirone, sertraline, and N Engl J Med 2019;380:1167-74.
DOI: 10.1056/NEJMcpc1900140
escitalopram were ineffective, but depression and anxiety symptoms diminished Copyright © 2019 Massachusetts Medical Society.
with the use of citalopram and clonazepam. The patient continued to use these
two medications to control his depression and anxiety, and he stopped seeing his
psychiatrist after almost 7 years of treatment, remaining under the care of his
primary care physician. Six years later, he discontinued citalopram.
One year later (20 months before this presentation), the patient contacted his
primary care physician to report recurrent anxiety, depression, and lethargy. Cita-
lopram was restarted. On evaluation in the primary care clinic 3 weeks later, he
reported that his condition had improved with the use of medication but lethargy
persisted. On examination, the blood pressure was 108/75 mm Hg, and the heart
rate 130 beats per minute and irregular. An electrocardiogram (ECG) and rhythm
strip (Fig. 1) showed new atrial fibrillation with a rapid ventricular response.
Treatment with metoprolol succinate and dabigatran was initiated, and during the
next 4 weeks, the metoprolol dose was adjusted to control the heart rate. Trans-
thoracic echocardiography revealed left atrial and left ventricular dilatation, a low-
normal left ventricular ejection fraction, mild left ventricular hypertrophy, and no
clinically significant valvular disease.
Four weeks later (18 months before this presentation), the patient was evalu-
ated in the cardiology clinic of this hospital; he reported daily episodes of palpita-
tions. The blood pressure was 140/60 mm Hg, and the heart rate 60 beats per
minute and regular. An ECG showed normal sinus rhythm with a slightly prolonged

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 The n e w e ng l a n d j o u r na l of m e dic i n e

II

Figure 1. Rhythm Strip.

A rhythm strip obtained during an outpatient visit shows atrial fibrillation with a rapid ventricular response.

corrected QT (QTc) interval, measuring 466 msec.
Holter monitoring for 24 hours was performed to
assess for control of the heart rate; the average
heart rate was 65 beats per minute, the maximum
heart rate was 84 beats per minute, and no epi-
sodes of atrial fibrillation were detected.
Approximately 1 year later (5 months before
this presentation), the patient reported several
weeks of heightened anxiety and recurrent de-
pressive symptoms, which were in part due to
financial stressors and the fact that his girl-
friend of several years had received a diagnosis
of recurrent cancer. The patient was binge drink-
ing intermittently. He reported weekly panic
attacks that were characterized by a “racing”
heart, light-headedness, restlessness, and shak-
ing; the panic attacks lasted 30 minutes and had
some correlation with episodes of increased al-
cohol intake. After 4 months of persistent symp-
toms, the patient sought psychiatry consultation.
One month later, on evaluation in the psy-
chiatry clinic, the patient described his mood as
depressed and anxious. He had persistent anxi-
ety and panic symptoms, as well as worsened
depressive symptoms, including difficulty concen-
trating, low energy, low self-worth, and sleeping
for 2 to 3 hours more than usual each night. He
reported having a stable appetite but had lost
6.4 kg during the preceding 18 months. He had
had no hallucinations or thoughts of harming
himself or others. He again reported weekly
panic attacks that were characterized by a racing
heart, light-headedness, restlessness, shaking,
and generalized weakness. Some of these epi-
sodes had lasted several hours. There were no
predictable triggers; the episodes had occurred
at all times of day and had occasionally awak-
ened him from sleep. He reported no chest pain
or dyspnea.
The patient’s medical history was notable for
atrial fibrillation, hypertension, hyperlipidemia,
asthma, gastroesophageal reflux, osteoarthritis,
colonic polyps, and vitamin D deficiency. He had
undergone appendectomy and knee arthroplasty.
He had had no psychiatric hospitalizations. Medi­
cations were citalopram, clonazepam, dabigatran,
metoprolol succinate, fluticasone, and albuterol.
Montelukast had caused an adverse reaction, and
sertraline had caused paresthesia.
The patient’s parents had a history of heavy
alcohol use. Several paternal relatives had a his-
tory of depression, and a maternal aunt had died
of an intentional drug overdose. His mother had
had emphysema and had died of breast cancer.
His father had had hyperlipidemia and had died
of asbestosis. The patient was born and raised in
New England. He had completed an undergradu-
ate degree and had worked at a university for 20
years; in the past year, because of financial
stressors, he had begun to work two jobs in re-
tail. The patient did not smoke cigarettes and
reported no illicit drug use. He reported drink-
ing 4 to 6 servings of whiskey weekly, with oc-
casional binges.
On examination, the blood pressure was
112/67 mm Hg, and the heart rate 64 beats per
minute and regular. The patient was well
groomed, alert, oriented, and cooperative. He had
fluent speech. His mood was sad and dysphoric,
and his affect was flat. His thought process was
goal-directed, and his attention was intact. He
had good insight into his worsening depressive
and anxiety symptoms. On review of laboratory
data obtained during the previous 5 months,
results of tests of thyroid function, kidney func-
tion, and liver function were normal, as were
electrolyte levels and the complete blood count.
Treatment with clonazepam and citalopram was
continued, and aripiprazole was initiated.
Three weeks after this presentation, the pa-
tient had fatigue and several episodes of palpita-
tions followed by near syncope. He had no chest
pain or dyspnea. He presented to the emergency
department of this hospital. The temperature
was 36.6°C, the blood pressure 163/92 mm Hg,
and the heart rate 120 beats per minute and ir-
regular. He appeared to be well. Results of uri-
nalysis, urine toxicologic testing, and kidney-

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 Case Records of the Massachuset ts Gener al Hospital
function tests were normal, as were electrolyte
and troponin T levels and the complete blood
count. An ECG showed atrial fibrillation with a
rapid ventricular response and nonspecific ST-
segment changes. Intravenous and oral diltiazem
were administered. While the patient was under-
going telemetry monitoring, he had two epi-
sodes of near syncope that correlated with sinus
pauses of 6 seconds and 7 seconds. He was ad-
mitted to the cardiology unit, and a dual-chamber
permanent pacemaker was placed. Metoprolol
succinate was continued, and the patient was
discharged home 2 days later.
Two weeks later, the patient was seen in the
psychiatry clinic. He reported marked improve-
ment in his mood and energy after the initiation
of aripiprazole; he did not report any further
episodes of anxiety or panic. He had stable hyper-
somnia, ongoing fatigue, and late-day mental “fog-
giness.” On evaluation at the primary care clinic
3 days later, the blood pressure was 124/82 mm Hg,
and the heart rate 69 beats per minute and regular.
Metoprolol was discontinued because of fatigue.
Three weeks later, the patient reported to his
psychiatrist that he had missed work because of
increasing anxiousness, with the feeling of a
racing and “thumping” heart and excessive worry.
He reported that aripiprazole was not controlling
his anxiety symptoms. He stated that his mood
was “good” and his energy, sleep, and appetite
were unchanged, but he had noticed weakness
in his legs, restlessness, and some new diffi-
culty breathing in association with his anxiety
symptoms. The aripiprazole dose was increased.
Several days later, a diagnostic test was per-
formed.
Differ en t i a l Di agnosis
Dr. Justin A. Chen: This 62-year-old man had long-
standing psychiatric illnesses and more recent
cardiac problems, providing us with the oppor-
tunity to consider the complex interplay between
the two. The symptoms that occurred intermit-
tently in this patient during the year and a half
before his initial recent presentation to the psy-
chiatry clinic — including anxiety, a racing heart,
palpitations, restlessness, and fatigue — are not
specific to either a psychiatric or a cardiac diag-
nosis. This ambiguity necessitates that we con-
sider each of these categories when constructing
a differential diagnosis.
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The case presentation ends with the patient
describing numerous symptoms to his psychia-
trist, including “anxiousness, with the feeling
of a racing and thumping heart and excessive
worry,” as well as “weakness in his legs, restless-
ness, and some new difficulty breathing in as-
sociation with his anxiety symptoms.” How can
we best interpret this constellation of symp-
toms? Does the development of these symptoms
represent a psychiatric disorder, a medical dis-
ease, or both?
We can broadly divide the differential diagno-
sis into medical and psychiatric causes, bearing
in mind that the distinction between these cat-
egories is being increasingly eroded as we gain
a better understanding of the reciprocal heart–
brain axis, which is influenced by both physio-
logical and behavioral mechanisms.1 Since psy-
chiatric diagnoses are typically ruled out when
the symptoms are better accounted for by an
underlying medical condition or substance inges-
tion, I will start with potential medical diagnoses.
Medical Causes
Hyperthyroidism
Excessive production of thyroid hormone, which
is often associated with the autoimmune disorder
Graves’ disease, can cause many of the symp-
toms seen in this patient, including anxiety and
panic, muscle weakness, palpitations, and weight
loss. Hyperthyroidism most frequently occurs in
women older than 60 years of age and is associ-
ated with atrial fibrillation. Thyroid dysfunction
is a common medical cause of psychiatric symp-
toms that is considered when other supporting
physical symptoms are present. In this case, re-
sults of thyroid-function tests were normal, and
the patient did not have any other changes char-
acteristic of hyperthyroidism, such as heat intol-
erance, insomnia, diarrhea, goiter, or diaphoresis.
Nonetheless, it would be reasonable to perform
repeat tests for thyroid function, so as to not
miss this common and correctable condition.
Recurrent Atrial Fibrillation
Metoprolol was discontinued 3 weeks before the
patient presented to his psychiatrist with in-
creased anxiousness, weakness, dyspnea, and a
thumping heart. Atrioventricular nodal blockers,
such as beta-blockers and calcium-channel block-
ers, are routinely used to control the heart rate
in patients with atrial fibrillation.2 Patients in
1169
 The n e w e ng l a n d j o u r na l
whom atrial fibrillation episodes are correlated
with stress or anxiety may have greater symptom
relief with beta-blockers than with calcium-
channel blockers. This difference is thought to
be a result of the antiadrenergic effects of beta-
blockers.3 Therefore, discontinuation of the
beta-blocker could have triggered a recurrence
of atrial fibrillation in this patient, who was
most likely sensitive to stress. A dual-chamber
pacemaker would be expected to maintain the
patient’s ventricular heart rate within the pro-
grammed range; nonetheless, recurrent atrial
fibrillation could provoke tachycardia with a rate
as high as the maximal programmed rate of the
device (usually 120 to 130 beats per minute),
which could cause subjective feelings of discom-
fort, including a racing heart, palpitations, and
dyspnea.
Dilated Cardiomyopathy
Dilated cardiomyopathy is characterized by left
ventricular dilatation and contractile dysfunction.4
Symptoms of dilated cardiomyopathy are related
to congestive heart failure and can include dys-
pnea, decreased alertness, edema, cough, orthop-
nea, weakness, and palpitations. This diagnosis
would be supported by the findings of left atrial
and left ventricular dilatation on transthoracic
echocardiography performed 19 months before
presentation; however, the patient had a low-
normal left ventricular ejection fraction at that
time. In addition, the patient did not have a
known family history of cardiomyopathy, his
alcohol intake does not seem to have been high
enough to implicate alcoholic cardiomyopathy,
and he did not have other symptoms of heart
failure. Nonetheless, follow-up assessment of the
patient’s cardiac status is indicated.
Torsades de Pointes and Prolongation of the QT
Interval
Torsades de pointes is a potentially lethal poly-
morphic ventricular tachycardia that is caused
by abnormal cardiac repolarization and is asso-
ciated with hypokalemia, hypomagnesemia, and
prolongation of the QT interval on ECG. QT pro-
longation is an important consideration in this
case; this risk factor was detected while the pa-
tient was taking citalopram, which is associated
with QT prolongation and is the selective sero-
tonin-reuptake inhibitor (SSRI) that is most
likely to cause this ECG effect. At the time of
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of m e dic i n e
presentation, this patient was also taking other
medications that are associated with QT prolon-
gation, including aripiprazole and albuterol. Man-
ifestations of torsades de pointes include palpi-
tations, chest pain, syncope, seizure, and sudden
death. However, the patient’s pacemaker would be
expected to protect against bradycardia-induced
torsades de pointes.5
Other Medical Causes
Additional medical diagnoses to consider include
pulmonary embolus, temporal lobe epilepsy, pace-
maker dysfunction, pacemaker-mediated tachy-
cardia, and neuroendocrine tumors, such as
pheochromocytoma. However, these diagnoses
are unlikely in this case.
Psychiatric Causes
Panic Disorder
Which psychiatric diagnoses could be contribut-
ing to this patient’s symptoms? When he pre-
sented to the psychiatry clinic, he reported weekly
episodes of a racing heart, light-headedness, rest-
lessness, and shaking. These episodes occurred
without warning, lasted 30 minutes to several
hours, occasionally awakened him from sleep,
and were somewhat correlated with increased
alcohol intake. This description matches the
psychiatric syndrome of panic disorder, which is
an anxiety disorder that is characterized by re-
current, unexpected panic attacks.
Anxiety and cardiac illnesses have a complex
relationship owing to substantial symptom over-
lap. Symptoms of a panic attack — palpitations,
diaphoresis, dyspnea, nausea, and chest discom-
fort — are virtually identical to symptoms of
acute coronary syndromes or arrhythmias.1 Pa-
tients with anxiety have increased perception of
internal bodily sensations, or “interoceptive aware-
ness,”6 which means that they are more likely to
scan for and negatively interpret visceral cues,
such as subtle changes in heartbeat, breathing,
and other factors. In addition, placement of a
cardiac device such as a pacemaker may itself
provoke a panic disorder.7
Given this patient’s history of anxiety, his
most recent symptoms could reflect increased
somatic preoccupation that contributed to a panic
disorder. However, it would be highly unusual
for this disorder to manifest at 62 years of age,
since onset usually occurs during the third decade
of life unless it is specifically linked to pace-
 Case Records of the Massachuset ts Gener al Hospital

maker placement. Especially in view of the known can confer a predisposition to atrial fibrillation
history of clinically significant cardiac disease, while also resulting in autonomic instability and
other medical causes must be ruled out before a cardiac symptoms.
diagnosis of panic disorder can be made.
Substance Intoxication
Intoxication with stimulant drugs, such as co-
caine or amphetamines, can generate sympatho-
mimetic symptoms, including anxiety and rest-
lessness. However, the patient did not have other
symptoms of stimulant intoxication, such as in-
somnia, anorexia, tachycardia, or hallucinations.
In addition, he did not report any use of illicit or
nonprescribed substances, and recent urine toxi-
cologic testing was negative.
Substance Withdrawal
Withdrawal from alcohol or sedative hypnotic
agents (e.g., benzodiazepines) can also contrib-
ute to a state of autonomic arousal or instability,
as well as anxiety and panic. Again, in this case,
there is no mention of other associated symp-
toms, such as tremor, insomnia, psychomotor
agitation, or seizures. The patient’s history does
not seem to be consistent with physiological
dependence, and there is no indication that he
abruptly stopped using either alcohol or benzo-
diazepines. However, the patient had a history of
binge drinking, and it is often difficult to accu-
rately ascertain the true pattern of substance use
on the basis of either subjective or objective
measures. The patient’s alcohol use seems to
have been triggered by psychosocial stressors,
a factor that points toward the often complex
interplay among anxiety, alcohol use, and car-
diac dysfunction.
Summary
The best diagnosis would parsimoniously explain
this patient’s symptoms and the time course of
his illness. Given the recent discontinuation of
metoprolol, recurrent atrial fibrillation is a likely
explanation. Patients with anxiety and depres-
sion may have increased severity of atrial fibril-
lation symptoms, which is perhaps caused by in-
creased interoceptive awareness.8 Workup would
focus on assessment of the patient’s cardiac
status, including rhythm, structure, and contrac-
tile function. Repeat thyroid-function tests would
be performed. In addition, it may be useful to
inquire further about alcohol use, since it is a
common form of self-medication for anxiety and
Dr . J us t in A . Chen’s Di agnosis
Recurrent atrial fibrillation in the context of
generalized anxiety disorder and major depres-
sive disorder.
C a r diol o gy M a nagemen t
Dr. Leon M. Ptaszek: During a scheduled outpatient
visit, the patient reported that he was having
particularly intense anxiety. A 12-lead ECG ob-
tained at that time showed atrial fibrillation
with occasional premature ventricular contrac-
tions and a ventricular rate of 90 beats per min-
ute. This finding suggested the possibility that
his episodes of anxiety might be correlated with
recurrences of atrial fibrillation. Further discus-
sion with the patient confirmed that he had
been having daily variation in the intensity of his
symptoms. He was able to provide specific dates
and times at which his anxiety symptoms were
most intense.
On interrogation of the patient’s pacemaker
during this outpatient visit, results of all device-
integrity checks were within acceptable limits. A
review of arrhythmia events that had been re-
corded by the patient’s pacemaker was also per-
formed. Analysis of these events revealed a close
temporal correlation between reported episodes
of anxiety and recorded episodes of atrial fibril-
lation (Fig. 2). It was therefore determined that
atrial fibrillation, not anxiety, was responsible
for his most severe symptoms.
Although the patient was initially treated ac-
cording to a strategy for heart rate control, he
reported recurrence of atrial fibrillation symp-
toms even after adequate heart rate control was
established with a beta-blocker.2 Therefore, a
strategy for heart rhythm control was initiated,
with the goal of minimizing his symptom bur-
den.9 This strategy involved the initiation of so-
talol. The decision to proceed with sotalol was
based on several factors. Use of a class 1C anti-
arrhythmic drug, such as flecainide, was dis-
couraged because the patient’s history aroused
concerns about the possibility of myocardial
ischemia and cardiomyopathy.10 Amiodarone was
considered but was not selected because of con-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Atrial

Ventricular

Figure 2. Electrograms Obtained on Interrogation of the Pacemaker.

Electrograms recorded from the atrial and ventricular leads of the pacemaker are shown on separate channels. The electrograms were
recorded at 25 mm per second during an episode of atrial fibrillation that correlated with symptoms reported by the patient. The aver‑
age atrial heart rate during this episode was 368 beats per minute, and the average ventricular heart rate was 179 beats per minute.

cerns about long-term accumulation of toxic side
effects in a relatively young patient. After the
initiation of sotalol, the patient reported a marked
decrease in the number of symptomatic episodes
that he had previously attributed to anxiety. Sub-
sequent interrogation of his pacemaker con-
firmed a reduction in the frequency and dura-
tion of atrial fibrillation episodes.
Ps ychi at r y M a nagemen t
Psychiatric Medications and Arrhythmias
Dr. Christopher M. Celano: This case brings up sev-
eral important points about the relationship be-
tween depression and anxiety and atrial fibrilla-
tion. Depression and anxiety are common in
patients with atrial fibrillation. In cross-sectional
studies, depressive symptoms were associated
with an increased likelihood of atrial fibrilla-
tion,11 and patients with atrial fibrillation had
higher levels of trait (persistent) anxiety than
patients with hypertension.12 Furthermore, 8.4%
of patients with atrial fibrillation met criteria for
major depressive disorder at any given time13 —
a prevalence that is slightly higher than the
yearly prevalence of major depressive disorder in
the general population.14 Thus, the patient’s psy-
chiatric history of major depressive disorder and
generalized anxiety disorder is not surprising.
In addition, psychiatric symptoms have been
linked to the development and persistence of
atrial fibrillation. Specifically, anxiety after car-
diac surgery and panic disorder have been linked
to the development of atrial fibrillation.15,16 Among
patients with established atrial fibrillation, those
who had depression or anxiety had more severe
symptoms of atrial fibrillation8,17 and were more
likely to have a recurrence of atrial fibrillation
after ablation18 than those who did not have
depression or anxiety. This patient’s psychiatric
history may have increased his risk of initial de-
velopment of atrial fibrillation and of recurrence
after pharmacotherapy for atrial fibrillation.
Although definitive treatment in this case
involves treatment of atrial fibrillation, treatment
of the anxiety and depressive disorders is crucial
as well. Treatment of anxiety and depressive dis-
orders has a clear benefit from a psychiatric
standpoint,19,20 and treatment of depression may
also have cardiovascular benefits.21-23 Although
data on the use of depression and anxiety treat-
ments in patients with atrial fibrillation are
limited, results of studies involving patients with
heart disease suggest that the best treatment
option for this patient is either cognitive behav-
ioral therapy or an SSRI. Among patients with
coronary artery disease or heart failure, cogni-
tive behavioral therapy was associated with great-
er reductions in psychiatric symptoms than con-
trol interventions.21,24,25 The use of SSRIs, including
citalopram, has led to reductions in depressive
symptoms in patients with coronary artery dis-
ease26,27 but appears to be less helpful in patients
with heart failure.28,29 Among patients with coro-
nary artery disease, the use of SSRIs and depres-
sion treatments may also reduce the risk of fu-
ture adverse cardiac events or death.21-23 Given
the patient’s positive response to citalopram in
the past and the potential psychiatric and cardio-
vascular benefits of psychiatric treatment in pa-
tients with heart disease, the choice of citalopram
seems reasonable. Monitoring for side effects of

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 Case Records of the Massachuset ts Gener al Hospital

citalopram, including bleeding and prolongation reproduced in multiple studies, and citalopram
of the QT interval,30,31 may be advised, but the causes more severe QT prolongation than placebo
benefits of depression and anxiety treatment in and other SSRIs,30,38-41 but there is little evidence
this situation most likely outweigh the risks as- that the use of citalopram leads to an increased
sociated with citalopram. risk of torsades de pointes or sudden cardiac
death.42,43 Furthermore, evidence suggests that re-
Effects of Medications on the QT Interval flexively lowering the dose of citalopram in re-
Dr. Scott R. Beach: All antipsychotic agents have sponse to concerns about QT prolongation, which
been associated with prolongation of the QT is a common practice, has led to increased psy-
interval, but this effect is thought to be most chiatric hospitalizations, increased prescriptions
severe with the use of low-potency phenothia­ for sedative and hypnotic agents, and no change
zines, such as thioridazine. In contrast, aripipra- in cardiac outcomes or all-cause mortality.44-47
zole, an atypical antipsychotic that has the Dr. Zebrowski: One month after the initiation
unique property of acting as a partial dopamine of sotalol, the patient had multiple episodes of
agonist, has been shown to cause the least se- breakthrough atrial fibrillation. He was readmit-
vere QT prolongation.32,33 Although two case re- ted to the hospital for monitoring while the
ports have linked aripiprazole to QT prolonga- sotalol dose was increased. During the next
tion or torsades de pointes, both reports involved 6 months, his mood continued to improve, and
patients with other risk factors and potential he had no clinically significant anxiety or recur-
confounders.34,35 It is challenging to stratify the rence of palpitations or fatigue. In the 5 months
risks of antipsychotics, but in terms of the risk thereafter, a prostate nodule was found on physi-
of QT prolongation, aripiprazole appears to be cal examination, and biopsy confirmed a diag-
safer than most other members of the class. nosis of prostate cancer. The patient had a mild
Among antidepressant agents, tricyclic anti- increase in anxiety but had no recurrence of
depressants are most classically associated with depression and no physical symptoms related to
QT prolongation because of their blockade of anxiety.
sodium channels. SSRIs have largely been con-
sidered to be safe in this regard and have been Fina l Di agnosis
well studied in cardiac populations. The use of
citalopram, the SSRI with the greatest potential Symptomatic atrial fibrillation with associated
for QT prolongation, is not recommended at anxiety.
doses of more than 40 mg daily or at doses of This case was presented at Psychiatry Grand Rounds.
more than 20 mg daily in patients older than Dr. Ptaszek reports receiving consulting fees from Abbott
Medical and WorldCare Clinical and fees for serving on a speak-
60 years of age or with liver dysfunction.36 Ad- ers’ bureau from Biotronik; and Dr. Celano, receiving lecture
ministration of citalopram at a dose of 20 mg fees from Sunovion and fees for providing expert testimony
daily led to QT prolongation by 8.5 msec, and from Dixon and Associates. No other potential conflict of inter-
est relevant to this article was reported.
administration at 60 mg daily led to QT prolon- Disclosure forms provided by the authors are available with
gation by 18.5 msec. These findings have been the full text of this article at NEJM.org.
37

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