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Commonly Used Antibiotic Can Cause Serious Psychiatric Side Effects

Worst Pills, Best Pills Newsletter article November, 2016

Many prescription drugs can cause serious psychiatric symptoms, including anxiety, confusion, depression, mania and psychosis.[1] Among the drugs associated with such side effects is the antibiotic clarithromycin (BIAXIN, PREVPAC).

Soon after clarithromycin’s approval by the Food and Drug Administration (FDA) in 1991, reports of patients developing psychiatric symptoms while using the antibiotic began appearing in medical journals (see box, for examples).[2],[3] At least two dozen journal articles describing such cases have been published to date.

A recent well-designed observational study in JAMA Internal Medicine provides the strongest evidence to date that clarithromycin can cause serious psychiatric symptoms. More importantly, it offers the first estimates of the magnitude of this risk.

Examples of Psychiatric Symptoms Linked to Clarithromycin
Here are a few summaries of published case reports from medical journals of patients who experienced significant psychiatric symptoms while taking clarithromycin (BIAXIN, PREVPAC):
A 21-year-old man was started on clarithromycin as part of a clinical trial. Before he started the drug, his mental status was normal. During the following week, the man became hyperactive and psychotic. His symptoms included anxiety and delusions of grandeur. He was seen by a psychiatrist and treated with an antipsychotic drug, which soon caused an adverse muscle reaction. The clarithromycin was discontinued 11 days after being started, and his psychiatric symptoms quickly resolved. Two weeks later, he resumed clarithromycin, and within a few days he again became agitated and psychotic. The clarithromycin was stopped, and his mental state returned to normal over the next few days.[4] A 56-year-old patient was prescribed clarithromycin for acute bronchitis. Within 24 hours of starting the antibiotic, he developed visual hallucinations, including a constantly changing landscape of sharks, priests and red lines. The patient was so frightened that he was unable to sleep. He continued to take the antibiotic for two days before being hospitalized. The drug was immediately discontinued, and over a period of three days, the hallucinations gradually disappeared.[5] A 49-year-old woman was prescribed clarithromycin, amoxicillin and lansoprazole (PREVACID) for bloating and stomach pain due to Helicobacter pylori infection. Because of a pharmacy error, she was initially given ciprofloxacin (CIPRO) instead of clarithromycin. One week later, her doctor detected the error, and the ciprofloxacin was stopped and clarithromycin begun. Two days after switching to clarithromycin, the patient experienced multiple psychiatric symptoms, including personality changes, progressive agitation and paranoid thoughts, especially persecutory delusions. She became suspicious of her husband, thinking he was going to leave her. She also had hallucinations in which she saw and spoke to her neighbor’s deceased daughter. After several days of worsening symptoms, her family took her to the emergency room, and she was hospitalized for psychiatric evaluation. Forty-eight hours after her last dose of clarithromycin, her mental state returned to normal.[6]

Examples of Psychiatric Symptoms Linked to Clarithromycin

Here are a few summaries of published case reports from medical journals of patients who experienced significant psychiatric symptoms while taking clarithromycin (BIAXIN, PREVPAC):

A 21-year-old man was started on clarithromycin as part of a clinical trial. Before he started the drug, his mental status was normal. During the following week, the man became hyperactive and psychotic. His symptoms included anxiety and delusions of grandeur. He was seen by a psychiatrist and treated with an antipsychotic drug, which soon caused an adverse muscle reaction. The clarithromycin was discontinued 11 days after being started, and his psychiatric symptoms quickly resolved. Two weeks later, he resumed clarithromycin, and within a few days he again became agitated and psychotic. The clarithromycin was stopped, and his mental state returned to normal over the next few days.[4]
A 56-year-old patient was prescribed clarithromycin for acute bronchitis. Within 24 hours of starting the antibiotic, he developed visual hallucinations, including a constantly changing landscape of sharks, priests and red lines. The patient was so frightened that he was unable to sleep. He continued to take the antibiotic for two days before being hospitalized. The drug was immediately discontinued, and over a period of three days, the hallucinations gradually disappeared.[5]
A 49-year-old woman was prescribed clarithromycin, amoxicillin and lansoprazole (PREVACID) for bloating and stomach pain due to Helicobacter pylori infection. Because of a pharmacy error, she was initially given ciprofloxacin (CIPRO) instead of clarithromycin. One week later, her doctor detected the error, and the ciprofloxacin was stopped and clarithromycin begun. Two days after switching to clarithromycin, the patient experienced multiple psychiatric symptoms, including personality changes, progressive agitation and paranoid thoughts, especially persecutory delusions. She became suspicious of her husband, thinking he was going to leave her. She also had hallucinations in which she saw and spoke to her neighbor’s deceased daughter. After several days of worsening symptoms, her family took her to the emergency room, and she was hospitalized for psychiatric evaluation. Forty-eight hours after her last dose of clarithromycin, her mental state returned to normal.[6]

Drug overview

Clarithromycin is a member of the macrolide family of antibiotics, which also includes azithromycin (ZITHROMAX, ZMAX) and erythromycin (E.E.S., ERYPED, ERY-TAB, ERYC, PCE). It is approved by the FDA to treat certain bacterial infections in many parts of the body, including pneumonia occurring outside the hospital setting, acute sinusitis, acute worsening of chronic bronchitis and skin infections.

Clarithromycin also is approved to treat patients who have ulcers in the duodenum (the first part of the small intestine connected to the stomach) caused by infection with the bacterium Helicobacter pylori (H. pylori). H. pylori infection also causes chronic gastritis (inflammation of the inner lining of the stomach), stomach ulcers and stomach cancer.[7] The infection is the most common chronic bacterial infection worldwide.[8]

For patients with H. pylori infection and duodenal ulcers (or other conditions caused by such infections), clarithromycin is routinely combined with another antibiotic and a proton pump inhibitor (PPI), such as lansoprazole (PREVACID). PREVPAC is a combination pill containing clarithromycin, the penicillin antibiotic amoxicillin and lansoprazole. It is approved specifically for treating patients with H. pylori infection and duodenal ulcers. There are at least two generic versions of this combination pill. Although the combination pill makes treatment more convenient, it may be cheaper to take generic versions of each of these three drugs.

For most of clarithromycin’s approved uses, including the treatment of H. pylori infections, a typical treatment course lasts seven to 14 days.

For the new JAMA Internal Medicine study, published in June 2016, researchers focused on patients treated for H. pylori with drug regimens that included clarithromycin.

The new research[9]

Using detailed electronic medical records from a health care system serving more than 7 million residents of Hong Kong, the researchers identified all adults who had received an outpatient prescription for triple-drug H. pylori therapy containing clarithromycin from 2003 to 2012 (approximately 66,600 patients).

For this patient group, they then identified all acute neuropsychiatric problems (mental health disorders caused by diseases of the nervous system) that resulted in hospital or emergency room admission. These problems included psychosis, delirium, mood disorders, sleep disturbances and cognitive impairment (such as problems with thinking, remembering information or decision-making).

For their analysis, the investigators calculated the rate of neuropsychiatric problems during the 14-day period following the start of a clarithromycin prescription — the usual maximum length of treatment. They then compared this rate to the rate of such episodes during a baseline period more than 14 days before the start of treatment.

Among the 66,600 study patients, a total of 1,824 neuropsychiatric problems occurred, including 354 psychotic episodes and 726 cognitive impairment incidents. The risk of having any type of neuropsychiatric problem was more than four times higher during the clarithromycin treatment period than during the baseline period. Moreover, the risk of having a psychotic episode during the treatment period was more than five times higher, and the risk of having a significant cognitive impairment was nearly three times greater. In contrast, there was no increase in the risk of these problems during the two weeks immediately before the start of treatment, or the two weeks immediately after the treatment ended.

These findings provide strong evidence that clarithromycin causes a sudden increase in the risk of serious adverse neuropsychiatric problems, but this increased risk disappears once the drug is stopped.

It is important to recognize that the increased probability of having one of these problems while taking clarithromycin is very small. For example, the researchers estimated that approximately one additional patient experienced an adverse neuropsychiatric event for every 2,200 patients using the drug.

What You Can Do

Public Citizen’s Health Research Group designates clarithromycin as Limited Use because its benefits outweigh its risks for treating certain infections, including H. pylori.

If you or a loved one is prescribed clarithromycin, be alert for signs of abnormal behavior or thinking. Assume that any new psychiatric symptoms that develop while taking clarithromycin are caused by the drug unless and until another cause is found. If such symptoms occur, contact the prescribing health care practitioner immediately to discuss changing to a different antibiotic and to arrange further evaluation as needed.

References

[1] Drug induced psychiatric symptoms (part 2). WorstPills.org. November 2002. /newsletters/view/58. Accessed August 20, 2016.

[2] Wallace RJ, Brown BA, Griffith DE. Drug intolerance to high-dose clarithromycin among elderly patients. Diagn Microbiol Infect Dis. 1993;16(3):215-221.

[3] Nightingale SD, Koster FT, Mertz GJ, Loss SD. Clarithromycin-induced mania in two patients with AIDS. Clin Infect Dis. 1995;20(6):1563-1564.

[4] Nightingale SD, Koster FT, Mertz GJ, Loss SD. Clarithromycin-induced mania in two patients with AIDS. Clin Infect Dis. 1995;20(6):1563-1564.

[5] Steinman MA, Steinman TI. Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis. Am J Kidney Dis. 1996;27(1):143-146.

[6] Dinca EB, Skinner A, Dinca RV, Tudose C. The dangers of gastritis: a case of clarithromycin-associated brief psychotic episode. J Nerv Ment Dis. 2015;203(2):149-151.

[7] Crowe SE. Bacteriology and epidemiology of Helicobacter pylori infection. Updated May 11, 2016. UpToDate. https://www.uptodate.com/contents/bacteriology-and-epidemiology-of-helicobacter-pylori-infection. Accessed August 21, 2016.

[8] Ibid.

[9] Wong AY, Wong IC, Chui CS, et al. Association between acute neuropsychiatric events and Helicobacter pylori therapy containing clarithromycin. JAMA Intern Med. 2016;176(6):828-834.

Commonly Used Antibiotic Can Cause Serious Psychiatric Side Effects

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