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A Case of Ciprofloxacin-Induced Acute Polymorphic Psychosis With a Distinct Deficit in Executive Functions

TO THE EDITOR: We present the case of a 45-year-old female patient who developed an acute polymorphic psychosis after treatment with the antibiotic ciprofloxacin.

A 45-year-old female patient developed an acute polymorphic psychosis over the course of 4 weeks in a rapidly progressive manner. Ciprofloxacin therapy had been initiated because of cystitis. The patient took 500 mg ciprofloxacin per day for 1 week.

At the end of the antibiotic treatment, she developed ideas of reference. At this time, she was working in a fashion shop and suspected that she was being watched by colleagues. Two weeks later, the patient suffered from lack of concentration and incoherent thinking. Her mood was very labile and often aggressive, and she suffered a "nervous breakdown" at her job. An emergency ambulance brought her to the University Hospital of Mannheim, where she found the behavior of the nurses and physicians "odd and bizarre." She was urged by her boyfriend to seek psychiatric treatment.

On admission, the patient was alert, but showed concentration deficits. Her thinking was concrete and incoherent. She had ideas of reference and ideas of persecution. She experienced auditory hallucinations and auditory illusions. Her mood was labile.

A neurological examination was normal. Brain MRI, EEG, laboratory diagnosis, and lumbar puncture revealed no abnormalities. The Wisconsin Card-Sorting Test, the Trail-Making Test, the d2-Brickenkamp Test, and a verbal subset of the Wechsler Memory Scale showed severe abnormalities of executive functioning. The Stroop test was within the normal range, at the lowest limits.

We started antipsychotic treatment with 15 mg aripiprazole. Within 9 days, the patient showed decreased ideas of persecution and started working at her former job again. The patient left our inpatient unit and continued working. Three to 4 weeks thereafter, she discontinued the medication. During an episode of stress at her workplace and in her relationship, she developed a depressive episode with pronounced ideas of reference. We therefore cannot rule out the possibility of a schizo-affective disorder. However, there was an exceptionally strong relationship between the onset of the psychotic symptoms and the initiation of ciprofloxacin therapy.

From a clinical point of view, our patient’s case underscores the importance of a detailed drug history, and, from a more psychopharmacological viewpoint, we hypothesize that the ciprofloxacin-induced psychosis shares aspects with an NMDA-antagonist–induced psychosis. Side effects of fluoroquinolones in the central nervous system (CNS) are well known. Jüngst and Mohr¹ report an incidence of 0.89% for CNS side effects; Hollweg et al.² report three cases of ciprofloxacin-induced psychosis among a population of 4,189 patients at a university hospital.

A PubMed search, however, revealed only a small number of relevant case reports, if we take into account that ciprofloxacin is one of the most widely-used antibiotics for indications like cystitis or bronchitis.^2,3 The case presented here shows a strong temporal relationship between the onset of the paranoid psychosis and the antibiotic course with ciprofloxacin. Ciprofloxacin is a fluoroquinolone, and this class of drugs shows some interesting psychopharmacological features.

Ciprofloxacin leads to an up-regulation of glutamatergic neurotransmission, mimicking NMDA-antagonists. A recent fMRI study in healthy probands showed that the NMDA-antagonist ketamine induces a distinct deficit of the prefrontal cortex,⁴ a deficit that parallels the one seen in our patient. As a consequence of this, we hypothesize that ciprofloxacin induced a deficit in prefrontal-mediated executive functions via enhanced glutamate neurotransmission. Our case lends some clinical support for the hypothesis that ciprofloxacin gains its psychosis-inducing properties via a glutamate-induced disruption of frontal executive functions. The case highlights the need for a better understanding of the CNS side effects of commonly used antibiotics. Aripiprazole, an antipsychotic with a new mechanism, showed a fast onset of action, and—considering the rapid onset in our patient—seems to be a good choice for treatment of ciprofloxacin-induced psychosis.

REFERENCES

1. Jüngst G, Mohr R: Overview of postmarketing experience with ofloxacin in Germany. J Antimicrob Chemother 1988; 22(suppl C):167-175
2. Hollweg M, Kapfhammer HP: Paranoide Psychose nach Behandlung mit den Antibiotikum Ofloxacin. Psychiatr Prax 1996; 23:251[Medline]
3. McCue JD, Zandt JR: Acute psychoses associated with the use of ciprofloxacin and trimethoprim-sulfamethoxazole. Am J Med 1991; 90:528–529[Medline]
4. Honey RAE, Honey GD, O’Loughlin C, et al: Acute ketamine administration alters the brain responses to executive demands in a verbal working-memory task: an fMRI study. Neuropsychopharmacology 2004; 29:1203–1214[CrossRef][Medline]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Grimm, O. Articles by für Seelische, Z. Search for Related Content PubMed Citation Articles by Grimm, O. Articles by für Seelische, Z. Schizophrenia Spectrum Disorders Syndromes Secondary to General Medical Disorders Other Somatic Therapy

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