Available online at www.sciencedirect.

com

General Hospital Psychiatry 33 (2011) 82.e5 – 82.e7

Case Report

A man who wanted to commit suicide by hanging himself:

an adverse effect of ciprofloxacin
Amir I.A. Ahmed, M.D.a,c,⁎, Frank M.M.A. van der Heijden, M.D., Ph.D.b ,
Hanneke van den Berkmortel, M.D.b , Kees Kramers, M.D., Ph.D.c
a
Department of Elderly, GGZ-Noord-en Midden Limburg, 5803 AC, Venray, The Netherlands
b
Department of Adult Psychiatry, GGZ-Noord-en Midden Limburg, 5803 AC, Venray, The Netherlands
c
Department of Clinical Pharmacology and Toxicology, The Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Received 4 June 2010; accepted 6 July 2010

Abstract

In this case report, we describe a man who developed recurrent depression and suicidal ideation with a serious plan to commit suicide as
definite adverse effect of ciprofloxacin, which had been prescribed for recurrent prostatitis.
© 2011 Elsevier Inc. All rights reserved.

Keywords: Fluoroquinolone; Ciprofloxacin; Depression; Suicidal ideations; Central nervous system; Neuropsychiatric adverse effects

1. Introduction plans to commit suicide. The police arrived shortly thereafter

Ciprofloxacin is a second-generation fluoroquinolone that
binds to and inhibits the bacterial DNA gyrase. Many adverse
drug reactions (ADRs), including neuropsychiatric events,
have been reported due to fluoroquinolones. However, the
incidence of neuropsychiatric ADRs is generally considered
to be low. We describe a man who developed recurrent
depression and suicidal ideation with a serious plan to
commit suicide as an adverse effect of ciprofloxacin, which
had been prescribed for recurrent prostatitis.
2. Case report
A 53-year-old man was admitted to a psychiatric hospital
after a serious and detailed attempt at committing suicide by
hanging himself in his house. He had prepared a chair and a
piece of rope, fastened to the staircase banister to hang
himself. Unexpectedly, and during the preparations for a
suicide, his brother called, who informed the police about his
⁎ Corresponding author. Department of Clinical Pharmacology and
Toxicology, The Radboud University Medical Centre, P.O. Box 9101, 6500
HB Nijmegen, The Netherlands. Tel.: +31 24 3614639; fax: +31 24
3614214.
E-mail address: amirahmed1@hotmail.com (A.I.A. Ahmed).
0163-8343/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.genhosppsych.2010.07.002
and interrupted him while he was writing a farewell letter.
The patient had 1 year of episodes of recurrent depression
including anhedonia, crying fits, lack of energy, fatigue,
insomnia, anorexia, extensive worrying, feelings of guilt and
intense suicidal thoughts; totally three previous episodes,
including the current episode. Each episode was preceded by
1-week treatment with ciprofloxacin 500 mg twice a day for
prostatitis. The onset of depressive symptoms and suicidal
ideation started within 3 days after the use of ciprofloxacin and
disappeared within 3 to 5 weeks after he had stopped taking it.
Eleven years before the current episode, he experienced a
depressed mood for 1 year after the death of his wife, without
suicidal thoughts. He was treated with antidepressants for
1 month, but he stopped taking them because of gastroin-
testinal adverse effects. Two weeks before admission, he was
going through surgery for a cervical hernia, which was an
uncomplicated procedure. The patient did not see any
plausible reasons to wish to die. He did not feel bad from
the prostatitis and he was not socially isolated.
His medication history was significant for amlodipine
10 mg/day, which had been prescribed 10 years earlier for
hypertension. Physical and psychiatric examinations did not
reveal any abnormalities, except for a depressed mood. The
results of blood and urine tests were all normal. The patient
did not smoke or use alcohol.
82.e6 A.I.A. Ahmed et al. / General Hospital Psychiatry 33 (2011) 82.e5–82.e7

Table 1 of the Health Care Insurance Board, The Netherlands, 2010),

The Naranjo causality scale: a method for estimating the probability of because of their broad-spectrum antibacterial activity and
adverse drug reactions
safety profile [2,3]. Many ADRs, including the central
Question Yes No Don't Scoring nervous system (CNS) adverse effects, have been reported
know
due to ciprofloxacin [4-6]. However, the incidence of CNS
Are there previous conclusion +1 0 0 +1 adverse effects of fluoroquinolones is generally low, 1–2%
reports on this reaction?
[3,7]. LaSalvia et al. [8] recently reported in this journal a
Did the adverse event appear after +2 –1 0 +2
the suspect drug was administered? 75-year-old man who developed severe depression and
Did the adverse reaction improve +1 0 0 +1 suicidal ideation after taking the fluoroquinolone levoflox-
when the drug was discontinued acin, which had been prescribed for wound infection after
or a specific antagonist colorectal cancer resection.
was administered?
A suicide attempt had not been reported. His symptoms
Did the AR reappear when +2 –1 0 +2
drug was readministered? improved after the discontinuation of levofloxacin.
Are there alternate causes –1 +2 0 +2 The neuropsychiatric ADRs, such as depression, night-
[other than the drug] that could mares, hallucinations, dizziness, restlessness, psychosis,
solely have caused the reaction? mania and seizures, are relatively rare [7] and are asso-
Did the reaction reappear when a –1 +1 0 0
ciated with individual risk predisposing factors, such
placebo was given?
Was the drug detected in the blood +1 0 0 0 as comorbidity, organic brain disease and preexisting
[or other fluids] in a concentration psychiatric disorder.
known to be toxic? Elderly patients are especially at risk of ADRs, because of
Was the reaction more severe when +1 0 0 0 medical comorbidity, polypharmacy and drug–drug interac-
the dose was increased or less
tions [9]. However, our patient was relatively young and had
severe when the dose was decreased?
Did the patient have a similar reaction +1 0 0 +1 no comorbidity or polypharmacy. The underlying neurobi-
to the same or similar drugs in any ological mechanisms of these neuropsychiatric ADRs are not
previous exposure? fully understood. A previous positron emission tomography
Was the adverse event confirmed by +1 0 0 +1 study did not show any effect on cerebral glucose–oxygen
objective evidence?
uptake or on cerebral blood flow after oral administration of
Total score 10
ciprofloxacin [10].
Scoring: N9=definite adverse drug reaction (ADR); 5–8=probable ADR; The neuropsychiatric ADRs are probably induced by the
1–4=possible ADR; 0=doubtful ADR.
blockade of gamma-aminobutyric acid (GABA) receptor
binding, stimulation of interleukin-2 production, interactions
Three weeks before the current hospitalization, the last with the dopaminergic system and interactions with opioid
treatment with ciprofloxacin for recurrent prostatitis ended. [7,11,12]. Stahlmann [13] suggests that the neurotoxic
Within 1 week of admission, the patient reported complete effects of fluoroquinolones could be related to the activation
remission of complaints, while no antidepressants were of the N-methyl-D- aspartate receptor by chelating with
prescribed. Amlodipine was discontinued and replaced by magnesium and removing its channel-blocking effect.
perindopril, because it is known that amlodipine may Interestingly, the neuropsychiatric ADRs have also been
cause depression. During the follow-up, he was still free reported after the local use of the drug, as in the topical
from all symptoms. ciprofloxacin eye drops [14]. Drugs, including antibiotics,
Ciprofloxacin was suspected to cause the depressive that induce suicidal ideation are associated with an increased
episodes and suicidal ideation, because the patient was risk of suicide attempts [15].
neither depressed nor experiencing suicidal ideation before To our knowledge, this is the first case report describing
his treatment with ciprofloxacin began. Furthermore, he had someone who seriously tries to commit suicide owing to
no reason to wish to die. There are a few case reports in the ciprofloxacin. However, it is possible that other factors may
literature concerning neuropsychiatric ADRs due to cipro- have played a role in the development of depressions and the
floxacin, which will be discussed below. According to the suicidal thoughts.
Naranjo causality scale, a method for estimating the Ciprofloxacin is eliminated primarily by the kidney; it is a
probability of ADRs [1], the adverse effects were definitely potent inhibitor of cytochrome P450 (CYP) enzymes 1A2
caused by ciprofloxacin (Table 1). (strong inhibitor) and 3A4 (weak inhibitor), enzymes that
play a central role in the metabolism of drugs [16,17]. Thus,
ciprofloxacin can cause increased levels of other medications
3. Discussion that would be metabolized at that cytochrome. It is known
that the calcium antagonist amlodipine that the patient used
In the Netherlands, the prescription of ciprofloxacin to for hypertension may cause anxiety and depression [18].
patients has increased in recent years from 223 510 in 2004 to Amlodipine is also metabolized by CYP3A4 cytochrome;
350 000 prescriptions in 2009 (the Drug Information System this suggests that the inhibition of CYP3A4 cytochrome by
 A.I.A. Ahmed et al. / General Hospital Psychiatry 33 (2011) 82.e5–82.e7
ciprofloxacin may have resulted in delayed amlodipine
metabolism and elevated plasma concentrations of the drug.
Furthermore, previous studies have shown that depression
and psychosocial distress are common among patients with
chronic prostatitis [19-21]. However, the psychological
profile of patients before the onset of chronic prostatitis
symptoms, medication history and comorbidity has not been
reported; therefore, causality cannot be determined. Recent
reports have provided clear evidence of testosterone effects
on the brain. The testosterone-derived neurosteroid andros-
tanediol is a positive allosteric modulator of GABAA
receptors [22]. However, in our patient the blood test results
were all within the normal range.
4. Conclusion
In our patient, ciprofloxacin was the potential precipitat-
ing factor for three times in the occurrence of recurrent
depressive symptoms and suicidal ideation. However, this
does not exclude other factors that may have played a role.
Prescribers should be aware of the neuropsychiatric ADRs of
ciprofloxacin, even if the drug has recently been stopped,
because it may lead to serious problems.
References
[1] Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the
probability of adverse drug reactions. Clin Pharmacol Ther 1981;30
(2):239–45.
[2] Owens Jr RC, Ambrose PG. Clinical use of the fluoroquinolones. Med
Clin North Am 2000;84(6):1447–69.
[3] Owens Jr RC, Ambrose PG. Antimicrobial safety: focus on
fluoroquinolones. Clin Infect Dis 2005;41(Suppl 2):S144–57.
[4] Schacht P, Arcieri G, Hullmann R. Safety of oral ciprofloxacin: an
update based on clinical trial results. Am J Med 1989;87
(5A):98S–102S.
[5] Steinert T, Studemund H. Acute delusional parasitosis under treatment
with ciprofloxacin. Pharmacopsychiatry 2006;39(4):159–60.
[6] Agbaht K, Bitik B, Piskinpasa S, et al. Ciprofloxacin-associated
seizures in a patient with underlying thyrotoxicosis: case report and
literature review. Int J Clin Pharmacol Ther 2009;47(5):303–10.
82.e7
[7] Christ W. Central nervous system toxicity of quinolones: human
and animal findings. J Antimicrob Chemother 1990;26(Suppl B):
219–25.
[8] LaSalvia EA, Domek GJ, Gitlin DF. Fluoroquinolone-induced suicidal
ideation. Gen Hosp Psychiatry 2010;32(1):108–10.
[9] Olivier P, Bertrand L, Tubery M, et al. Hospitalizations because of
adverse drug reactions in elderly patients admitted through the
emergency department: a prospective survey. Drugs Aging 2009;26
(6):475–82.
[10] Bednarczyk EM, Adler LP, Remler B, et al. Assessment of the effects
of ciprofloxacin and nalidixic acid on cerebral blood flow and
metabolism in healthy subjects by positron emission tomography.
Pharmacotherapy 1994;14:153–61.
[11] Unseld E, Zeilger G, Gemeinhardt A, et al. Possible interaction of
fluoroquinolones with the benzodiazepine–GABA A-receptor com-
plex. Br J Clin Pharmacol 1990;30:63–70.
[12] Peeters BW, Vanderheyden PM. In vitro and in vivo characterization
of the NMDA receptor-linked strychnine-insensitive glycine site.
Epilepsy Res 1992;12(2):157–62.
[13] Stahlmann R. Clinical toxicological aspects of fluoroquinolones.
Toxicol Lett 2002;127(1-3):269–77.
[14] Radandt JM, Marchbanks CR, Dudley MN. Interactions of
fluoroquinolones with other drugs: mechanisms, variability, clinical
significance, and management. Clin Infectious Diseases 1992;14:
272–84.
[15] Robertson HT, Allison DB. Drugs associated with more suicidal
ideations are also associated with more suicide attempts. PLoS One
2009;4(10):e7312.
[16] McLellan RA, Drobitch RK, Monshouwer M, et al. Fluoroquinolone
antibiotics inhibit cytochrome P450-mediated microsomal drug
metabolism in rat and human. Drug Metab Dispos 1996;24:1134–8.
[17] Herrlin K, Segerdahl M, Gustafsson LL, et al. Methadone, cipro-
floxacin, and adverse drug reactions. Lancet 2000;356:2069–70.
[18] Zanchetti A, Omboni S, La Commare P, et al. Efficacy, tolerability,
and impact on quality of life of long-term treatment with manidipine or
amlodipine in patients with essential hypertension. J Cardiovasc
Pharmacol 2001;38(4):642–50.
[19] de la Rosette JJ, Ruijgrok MC, Jeuken JM, et al. Personality variables
involved in chronic prostatitis. Urology 1993;42:654–62.
[20] Berghuis JP, Heiman JR, Rothman I, et al. Psychological and physical
factors involved in chronic idiopathic prostatitis. J Psychosom Res
1996;41:313–25.
[21] Egan KJ, Krieger JN. Psychological problems in chronic prostatitis
patients with pain. Clin J Pain 1994;10:218–26.
[22] Reddy DS, Jian K. The testosterone-derived neurosteroid androstane-
diol is a positive allosteric modulator of GABA-A receptors.
J Pharmacol Exp Ther 2010.