Along with the four cases of suicidal behaviors in two men and two women, this article also reads: "Elderly patients have been found to have nearly 5-fold higher risk of completed suicide during the first month of therapy with SSRIs.3

Suicidal Ideation
Associated With
Duloxetine Use
A Case Series
To the Editors:
On May 2, 2007, the US Food and
Drug Administration expanded black box
warnings of all antidepressant medications
to include information about an increased
risk of suicidality in young adults aged 18
to 24 years. The advisory committee made
this decision after evaluating the results of
meta-analyses of participants enrolled in
372 randomized antidepressant trials over
the past 20 years.
A differential risk of antidepressant induced
suicidality among various age
groups has previously been reported in
the literature. Martinez et al
1 found
an increased risk of suicidality with selective
serotonin reuptake inhibitors
(SSRIs) compared with tricyclic antidepressants
in patients 18 years and
younger. Another case-control study
found that severely depressed patients
aged 6 to 18 years treated with antidepressants
were at a significantly
higher risk of suicide attempts and
completed suicides compared with
2 Elderly patients have been
found to have nearly 5-fold higher risk
of completed suicide during the first
month of therapy with SSRIs.
3 The
study also reported consistent results
when venlafaxine was included in the
analyses with SSRIs. Venlafaxine (which
inhibits reuptake of 5-hydroxytryptamine
[5-HT] and norepinephrine [NE] at
higher doses) shares a similar proposed
mechanism of action as duloxetine.
Duloxetine has been shown to have
100-fold higher affinity for human 5-
HT transporters and at least 300-fold
higher affinity for NE transporters in
vitro compared with venlafaxine.
5 It is
unknown whether more potent 5-HT and
NE blockade correlates with increased
suicidal ideation during initial antidepressant
Mr A is a 37-year-old married white
man admitted for a major depressive episode
after his wife discovered that he bought
equipment to poison himself with carbon
monoxide. Two months before admission,
the patient started treatment with duloxetine
for chronic back pain. The dose was later
increased to 60 mg/d for additional pain
relief. Two weeks before admission, duloxetine
was increased again to 90 mg/d. Seven
days later, the patient reported having
thoughts of suicide and was admitted to the
University of Kansas Medical Center psychiatry
unit in August 2005.
Mr A had no previous psychiatric
hospitalization or any outpatient psychiatric
care. Before taking duloxetine, Mr A had
never taken any psychotropic medications.
He did not have prior suicidal attempts or
suicidal ideations. No signs of character
pathology or poor impulse control were
elicited. The patient did have 3 first-degree
relatives with an affective disorder but no
family history of suicide.
Upon admission to inpatient psychiatry,
Mr A appeared severely distressed. He
continuously repeated the phrase: B
My wife
deserves better.[ Apparently, the patient
developed a romantic interest with a woman
at work. He denied any infidelity but started
having guilt about the thoughts. Mr A_
s target
symptoms also included anxiety, insomnia,
and irritability. The patient was unable to state
exactly why he wanted to commit suicide. Mr
A reported that he did not feel sad and could
think of no reason for him to wish to die. He
described a loving and supportive marriage.
Mr A was steadily employed with no recent
additional social stressors.
On Day 1 of hospitalization, duloxetine
was tapered off, and escitalopram was started.
The patient was also started on risperidone
1 mg at bedtime for psychic agitation. Within
days of discontinuing duloxetine, Mr A
reported decreased anxiety and no thoughts of
suicide. After 3 days, he was discharged home
on escitalopram and risperidone.
Mr B is a 63-year-old well-educated
married white man admitted to the University
of Kansas Medical Center psychiatry
unit in August 2005. The patient presented
with a chief complaint of B
I started having
thoughts of suicide.[ Mr B had a previous
history of major depressive disorder (MDD)
successfully treated with fluoxetine. Four
months before admission, the patient did
not feel depressed and stopped taking fluoxetine.
Depression reoccurred; 2 weeks before
admission, the patient was started on duloxetine
at an initial dose of 30 mg/d for mild
symptoms of depression (eg, fatigue, insomnia,
and sadness). The patient felt no
significant improvement, and duloxetine
dose was increased to 60 mg/d. During this
period, the patient was not taking any other
medications. The patient soon started having
obsessive thoughts about suicide together
with severe anxiety, insomnia, and irritability.
He was unable to explain why he was
having thoughts of wanting to die. Mr B then
sought the help of an outpatient psychiatrist,
and duloxetine was tapered off, and fluoxetine
was restarted. Two days later, the
patient expressed concern about having the
thoughts of suicide, and his psychiatrist
recommended inpatient hospitalization.
Upon admission, fluoxetine was
increased to 60 mg/d, and mirtazapine was
added at bedtime for depression and insomnia.
Five days after stopping duloxetine, the
patient reported decreased anxiety and no
longer had thoughts of death or suicide.
Mr B did not have a history of a
suicide attempt or any thoughts of suicide
before treatment with duloxetine. No symptoms
suggestive of character pathology or
poor impulse control were noted. The
patient did have a first-degree relative with
a history of suicide. Mr B described having
a loving and stable family. The patient did
experience a recent increase in workload
after a coworker was let go. He did not
attribute the depressive symptoms to work related
Ms C is a 39-year-old married white
woman with a 20-year history of MDD and
chronic fatigue syndrome. She was admitted
to inpatient psychiatry after she and her
husband became concerned about her worsening
depressive symptoms. This was her
first psychiatric hospitalization because her
depressive symptoms had been well controlled
with antidepressant monotherapy,
including fluoxetine and escitalopram (discontinued
by the patient 10 months before
admission). She had attempted suicide by
carbon monoxide poisoning 10 years before
this admission, escaping from her garage
after developing a headache.
Three months before admission, Ms C
had been started on duloxetine 30 mg/d.
Duloxetine was titrated to 90 mg/d over the
next 4 weeks. She reported experiencing
almost no change in her depressive symptoms
but had noticed an improvement in
weakness and pain associated with chronic
fatigue syndrome. Duloxetine was increased
again to 120 mg/d. At a follow-up visit 6
weeks later, her depressive symptoms had
worsened; she felt more hopeless, worried,
and isolated, with increased anxiety and poor
sleep. Six days later, in February 2006, she
was admitted to the University of Kansas
Medical Center psychiatry unit.
At the time of admission, she reported
having thoughts of suicide and of her
children drowning in their swimming pool.
She emphatically denied any intentions of
killing her children but was filled with fear
that if they should drown, she would have
lost her remaining reason for wanting to live.
She reported feeling drugged[ and losing
control of her thoughts. Her husband
reported that these thoughts were uncharacteristic
of his wife and a source of great
concern. During treatment with duloxetine,
Ms C also developed a significant problem
with urinary retention. Duloxetine was
tapered over several weeks, resulting in an
abatement of the thoughts of suicide and her
children drowning and a resolution of urinary
Ms D is a 42-year-old white woman,
who was admitted to the Kansas City VA
Medical Center after she presented herself to
the mental hygiene clinic complaining of
increasing suicidal ideation for the previous
5 days. Two weeks before admission, the
patient had been switched from fluoxetine
40 mg/d to duloxetine 40 mg/d because of
persistent diarrhea. The patient reported
thoughts of poisoning herself in an enclosed
garage with carbon monoxide and thoughts
of overdosing with clonazepam. She reported
vivid flashbacks of experiences with her
former husband 20 years before when he
had threatened to kill himself by holding a
gun to his head. Ms D_
s target symptoms
also included decreased concentration,
decreased sleep, poor appetite, decreased
energy, anhedonia, and increased agitation.
Upon admission to inpatient psychiatry,
Ms D was quite tearful and reported that
this was the first time that she had ever had
thoughts of suicide. Ms D had no previous
psychiatric hospitalization. Ms D had been
diagnosed with MDD and posttraumatic
stress disorder in 1995. Previous treatment
had included citalopram, fluoxetine, bupropion,
gabapentin, and clonazepam. Current
medications included duloxetine 40 mg/d,
clonazepam, and naproxen. Upon admission,
duloxetine was discontinued, and fluoxetine
20 mg/d was restarted. Three days after
stopping duloxetine, the patient reported
having no thoughts of suicide, no insomnia,
and improved appetite. She was noted to be
interacting well with peers and staff. She
reported that her mood was positive, and she
felt 100%[ better after restarting fluoxetine.
Subsequently, Ms D was discharged home on
her third hospital day.
The authors present 4 cases that
illustrate a close temporal relationship
between the development of acute suicidal
ideation and duloxetine use. In all
4 cases, suicidal thoughts appeared after
increasing duloxetine dosages and subsided
after discontinuing use. The
patients were medically stable, with
laboratory results within normal limits.
None had recent substance abuse or
dependence. No extrapyramidal symptoms
were noted.
Duloxetine is currently approved
by the Food and Drug Administration
for treatment of MDD, generalized
anxiety disorder, and diabetic peripheral
neuropathic pain. Multiple clinical
trials have demonstrated efficacy of
duloxetine for treatment of stress urinary
incontinence and fibromyalgia.
A review of controlled studies of duloxetine
for MDD found no difference
between duloxetine and placebo in
respect to measures of suicidal ideation
and behaviors.
10 However, it is unclear
what exclusion criteria in regard to
suicidal ideation or behaviors were
applied to patients entering these studies.
It is also unknown whether the
results would have been different if
non-MDD duloxetine clinical trials
were included in the analysis.
To our knowledge, this is the first
case series to describe development of
suicidal preoccupation in conjunction
with duloxetine use. Clinicians should
carefully monitor patients for emergence
of suicidal ideation when prescribing any
antidepressant, with particular scrutiny
during periods of initial use and dosage
Aashish R. Parikh, MD
Benjamin T. Thatcher, DO
Ely A. Tamano, MD
Barry I. Liskow, MD
Department of Psychiatry
and Behavioral Sciences
The University of Kansas Medical Center
Kansas City, KS
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Antidepressant treatment and the risk of fatal
and non-fatal self harm in first episode depression:
nested case-control study. BMJ
. 2005;
2. Olfson M, Marcus SC, Shaffer D. Antidepressant
drug therapy and suicide in severely
depressed children and adults: a case-control
study. Arch Gen Psychiatry. 2006;63:865–872.
3. Juurlink DN, Mamdani MM, Kopp A, et al.
The risk of suicide with selective serotonin
reuptake inhibitors in the elderly. Am J
Psychiatry. 2006;163:813–821.
4. Tatsumi M, Groshan K, Blakely RD, et al.
Pharmacological profile of antidepressants
and related compounds at human monoamine
transporters. Eur J Pharmacol. 1997;340:
5. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld
PG, et al. Comparative affinity of duloxetine
and venlafaxine for serotonin and norepinephrine
transporters in vitro and in vivo,
human serotonin receptor subtypes, and other
neuronal receptors. Neuropsychopharmacology
6. Norton PA, Zinner NR, Yalcin I, et al.
Duloxetine versus placebo in the treatment of
stress urinary incontinence. Am J Obstet
Gynecol. 2002;187:40–48.
7. Dmochowski RR, Miklos JR, Norton PA,
et al. Duloxetine versus placebo in the
treatment of North American women with
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8. van Kerrebroeck P, Abrams P, Lange R, et al.
Duloxetine versus placebo in the treatment
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9. Lilly-sponsored duloxetine clinical studies.
Available at:
Accessed May 16, 2007.
10. Acharya N, Rosen AS, Polzer JP, et al.
Duloxetine: meta-analyses of suicidal behaviors
and ideation in clinical trials for major
depressive disorder. J Clin Psychopharmacol.