Article - Ciprofloxacin-Induced Manic Episode

[Guest guest]

Ciprofloxacin is among the most frequently prescribed

antimicrobials; however, its neuropsychiatric effects

are not thoroughly known. Although there have

been previous isolated mentions in the literature of fluoroquinolones, and ciprofloxacin,

specifically, precipitating central nervous system disturbances, We believe that this is the first report of

ciprofloxacin-induced mania.

" Mr.

M " is a 28-year-old white man with a history of primary sclerosing cholangitis and

controlled ulcerative colitis treated with sulfasalazine. He was admitted to the hospital after onset of

painless jaundice, pruritis, fatigue, and anorexia. Endoscopic retrograde cholangiopancreatogram

(ERCP) demonstrated distal common bile-duct stricture, and initial stenting was unsuccessful. Thereafter,

he developed clinical signs of suppurative cholangitis. Four days

later, a second ERCP stenting proceeded successfully.

Postoperative

treatment was metronidazole 500 mg IV bid, cefazolin 1 g IV q8h, ciprofloxacin 400 mg IV

bid, gravol 25 mg–50 mg q4h, ursodeoxycholic acid 1,500 mg po

bid, and folate 1 mg po

od. On Postoperative Day 1,

sulfasalazine 300 mg po tid

was added and increased the next day to his pre-admission dose of

1,000 mg po tid. The patient quickly improved clinically, and was

discharged with stable vital signs on Postoperative Day 5. All medications were discontinued except ciprofloxacin, to

be continued at 500 mg po bid.

The

next day, Mr. M was returned to the hospital by police because he

was reported to be agitated and violent. On

assessment, he demonstrated significant irritability, expansiveness,

and grandiosity, in that he wanted to publish a book and run a

(religious) mission.

The

patient was negative for substances, alcohol, head injury, depression,

anxiety disorder, dementia, and previous manic episode. He

had had no previous psychiatric admissions. He was

prescribed piperacillin-plus-tazobactam

4.5 g IV qid, thiamine 100 mg IV/IM, and

acyclovir 600 mg IV q8h. Ciprofloxacin was stopped,

and haloperidol 5 mg IM q 4h–6h prn

and lorazepam 1 mg SL q8h prn were prescribed for agitation.

Beyond

chronic hepatic-enzyme elevations, all laboratory values were

normal, as were serum protein electrophoresis, thyroid-function tests,

vitamin B12, folate, and CA19-9 (tumor

marker) levels. Psychiatric consultation

ruled out delirium caused by a general-medical condition.

The

patient fulfilled criteria for a medication-induced mania episode,

and was treated with olanzapine 5 mg bid. Haloperidol was decreased to 2.5 mg po/IM q2h prn for agitation

(maximum: 10 mg/day). Lorazepam

was replaced with prn zoplicone

(3.75 mg qhs prn

[maximum: 7.5 mg/day]) for sleep, and all other medications were

stopped. On follow-up the next day, the patient showed

increased delusional content and expansive mood. The

olanzapine dosage was increased to 5 mg po qA.M. and

7.5 mg qhs. Two days later,

olanzapine was again increased, to 5 mg qA.M. and 10 mg qhs. Initial clinical improvement

in behavior was noted by the psychiatry department by Postoperative

Day 12. The patient did well thereafter,

and his condition continued to improve gradually.

By

Postoperative Day 15, psychiatric evaluation described him as alert

and oriented, with no delusions or persisting hostility, and with

insight into his previous mental disturbance. He was

discharged from the hospital with a short-term prescription for

olanzapine po. The discharge diagnosis was " medication-induced manic

episode, " which may or may not have been a part of a bipolar affective

disorder, type 1.

Discussion

New-onset

mania or psychosis in adult patients with no previous history of

mental illness should prompt a clinician to search for reversible

causes. Our patient had no previous psychiatric history,

nor signs of infection, encephalitis, metabolic abnormalities, acute

organic condition, or other factors, such as substance-abuse or drug

interactions that might account for the acute onset of his temporary

mania and his subsequent recovery.

There

was a clear relationship between the onset of psychiatric symptoms

and ciprofloxacin treatment, and initial signs of gradual recovery

occurred 6 days after ciprofloxacin was discontinued. Absent

a re-challenge with ciprofloxacin, the temporal relationship between

the patient’s ciprofloxacin use and the onset and resolution

of his mania strongly suggests a causal relationship.

There

have been previous reports of psychosis induced by ciprofloxacin, as

well as delirium induced by other fluoroquinolones. A recent review of cases of mania caused by antibiotics

suggested that reports of mania are increasing with the introduction

of newer antibiotics and the heightened frequency with which they

are prescribed. This is the first report

suggesting that mania may persist after discontinuation of the

antibiotic and that this can be treated with an atypical neuroleptic.

Most

cases previously reported responded quickly to discontinuation of

the offending agent, and it seemed that they did not require neuroleptic treatment. In more

complicated or persistent presentations such as Mr. M’s,

however, we believe that augmentation with atypical neuroleptics and close follow-up may be an important second-line

therapy.

[Guest guest]

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Interesting article -- I had an interesting bout with Cipro -- it

seemed to cause central nervous system suppression. Very weird.

Penny

In , " Barb Henshaw " wrote:

>

> Ciprofloxacin is among the most frequently prescribed antimicrobials;

> however, its neuropsychiatric effects are not thoroughly known. Although

> there have been previous isolated mentions in the literature of

> fluoroquinolones, and ciprofloxacin, specifically, precipitating central

> nervous system disturbances,