Psychiatric Bulletin (2004) 28: 98-99. doi: 10.1192/pb.28.3.98
© 2004 The Royal College of Psychiatrists
Psychiatric Bulletin (2004) 28: 98-99
© 2004 The Royal College of Psychiatrists
Drug information quarterly |
A case of clarithromycin psychosis
Fawad Elahi, Registrar
Ennis Psychiatric Unit, Shannon Health Centre, Shannon, Ireland
Moosajee Bhamjee, Consultant Psychiatrist
Shannon Day Hospital, Shannon Health Centre, Shannon, Ireland
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Abstract
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A 19-year-old woman developed an immediate psychotic reaction following
intravenous administration of clarithromycin. She responded to atypical
antipsychotic drugs but needed psychiatric hospitalisation. She recovered
after a year and is now symptom-free without any medication. This is a rare
side-effect, but needs to be recognised.
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Introduction
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A 19-year-old woman presented to her general practitioner in June 2002 with
a sore throat. A course of penicillin was prescribed but had to be
discontinued because she developed a rash. Difficulty in swallowing and a
continuing sore throat led to the patient being admitted to the medical ward
of a general hospital. Following confirmation of the diagnosis of acute
tonsillitis, a course of intravenous clarithromycin was prescribed.
Following the second dose of intravenous clarithromycin the next day, the
patient became psychotic and agitated with visual and auditory hallucinations,
and believed that she was in heaven: she could see the angels, she was walking
on clouds. She became disoriented for time, place and person and expressed
feelings of derealisation and depersonalisation. Antibiotic therapy was
stopped and immediately replaced by intravenous haloperidol and lorazepam; on
the third day the patient developed a dystonic reaction, which responded to
benzotropine. The patient was examined by the liaison psychiatrist who
continued the prescription of haloperidol, but her psychotic state persisted.
All her physical investigations were normal on assessment by the general
medical consultant physician and her tonsillitis had improved. On her fifth
day in hospital the psychotic symptoms were still present, and now the patient
felt that she was possessed and was the cause of other people’s deaths,
and could not be treated in a medical unit. This acute psychiatric reaction
could have been secondary to her acute physical illness, coincidental or a
reaction to the clarithromycin.
The patient was transferred to the psychiatric department at Ennis General
Hospital for further treatment of her acute psychotic state. In the unit, she
remained paranoid and perplexed, and admitted to auditory hallucinations in
the third person. She also smiled and laughed inappropriately. Haloperidol
administration was immediately stopped and atypical antipsychotic therapy with
risperidone (2 mg) was commenced.
The patient responded slowly and during her stay the psychotic symptoms
persisted, but with a gradual improvement noted every few days by the nursing
staff and the patient’s family. All routine blood investigations were
normal when repeated in the psychiatric unit and no cerebral abnormality was
detected by computed tomography. A lumbar puncture was not done. The patient
was discharged home after a month of treatment in the acute psychiatric unit
with a diagnosis of acute psychosis secondary to an unusual reaction to
clarithromycin, even though her illness was schizophreniform in type. Her
medication on discharge was risperidone 3 mg at night.
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Medical history
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There was no family history of psychiatric illness, and the patient did not
have any premorbid symptoms of schizophrenia or of any psychiatric illness;
she was a bubbly, extroverted college student who never misused drugs or
alcohol.
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Out-patient treatment
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The young woman and her family were reviewed every few weeks in the clinic.
Her family were informed of all our views and participated in all clinical
decisions. As the patient returned to normal life and community living, her
risperidone dosage was gradually reduced over a period of 6 months. She
returned to college but noted a problem with memory for names, places and
events, especially of her time in the general hospital and the early days in
the psychiatric unit. This memory problem was confirmed by psychological
testing but has gradually resolved, except for memories of the time of the
acute onset of her psychosis.
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Present time
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The young woman is now able to continue with her academic studies, and is
able to complete her assignments and projects. She is mixing socially with
fellow students, and her personality has returned. Her family are pleased with
her progress. Her risperidone therapy has been stopped for 7 months (August
2003) and no adverse reaction has been reported. She continues to be reviewed
as an out-patient.
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Other cases
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Psychosis secondary to clarithromycin is a rare event and has been reported
in the medical literature. Adverse events have been reported in 4-30% of
patients, but worse effects on the nervous system have occurred in 3% of
patients including dizziness, anxiety, insomnia, bad dreams, confusion,
disorientation and hallucinations (Beers
& Berkow, 1999; Dukes &
Aronson, 2000). To confirm that this was a case of sensitivity to
clarithromycin would require another challenge, but this would be dangerous to
both patient and medical staff and would be merely an academic exercise.
Examples
A young patient with advanced AIDS experienced acute psychosis shortly
after taking clarithromycin. The psychosis was resolved on withdrawal but
recurred on a second challenge.
A 77-year-old man developed mania 6 days into treatment with clarithromycin
for a soft-tissue infection. His mania resolved on withdrawal.
A 56-year-old man with chronic renal insufficiency and underlying aluminium
intoxication maintained on peritoneal dialysis developed visual
hallucinations. These developed 24 h after the start of clarithromycin
administration for chest infection and resolved completely 3 days after
withdrawal of the drug. There is no clear evidence that neuropsychiatric
complications of clarithromycin develop more readily in uraemic patients, but
several factors may predispose towards these adverse effects, such as reduced
drug clearance, altered plasma protein binding, different penetration of drug
across the blood-brain barrier or an increased propensity for drug
interaction.
A 53-year-old man taking long-term fluoxetine and nitrazepam developed a
frank psychosis 1-3 days after starting to take clarithromycin for a chest
infection. His symptoms resolved on withdrawal of all three drugs and did not
recur with erythromycin or when fluoxetine and nitrazepam were restarted in
the absence of antibiotics. The symptoms might have been due to a direct
effect of clarithromycin or else inhibition of hepatic cytochrome P450
metabolism leading to fluoxetine toxicity. There are also two incidents
reported of patients who were being treated with clarithromycin for a
Helicobacter pylori infection.
The UK pharmacovigilance group the Committee on Safety of Medicines has had
17 reports since 1991 of paranoid delusional psychosis in relation to this
drug. There is speculation that these reactions may be under-reported. To date
the Irish Medicines Board has three reported cases of a similar kind.
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Conclusion
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A 19-year-old woman reacted to clarithromycin with the development of an
acute psychotic reaction, which responded to risperidone; she has now resumed
a normal life. The family were alarmed that their daughter entered a general
hospital as a normal young person and was discharged with a psychotic illness
5 days later. It frightens the family to think that their child could react in
this way to antibiotics and that a similar reaction might develop with other
antibiotics or if clarithromycin was prescribed again. The patient too is
frightened of a recurrence of the psychosis, and medically one wonders whether
she may now be prone to further psychotic episodes.
This case illustrates the importance of being vigilant before making a
diagnosis of schizophrenia, and the close relationship between general
medicine and psychiatry.
This is a rare event.
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References
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BEERS, M. H. & BERKOW, R. (1999) The
Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ:
Merck Publications.
DUKES, M. N. & ARONSON, J. K. (2000)
Meyler’s Side Effects of Drugs (14th edn). New
York: Elsevier Health Sciences.
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Abstract
Introduction
