Association Between Acute Neuropsychiatric Events and Helicobacter pylori Therapy Containing Clarithromycin | Gastroenterology | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.204.227.34. Please contact the publisher to request reinstatement.
1.
Ho  P, Wong  S. Reducing bacterial resistance with IMPACT. 4th ed. 2012. http://www.chp.gov.hk/files/pdf/reducing_bacterial_resistance_with_impact.pdf. Accessed September 7, 2015.
2.
Malfertheiner  P, Megraud  F, O’Morain  CA,  et al.  Management of Helicobacter pylori infection: the Maastricht IV/Florence Consensus Report.  Gut. 2012;61(5):646-664. PubMedGoogle ScholarCrossref
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.PubMedGoogle ScholarCrossref
4.
Pollak  PT, Sketris  IS, MacKenzie  SL, Hewlett  TJ.  Delirium probably induced by clarithromycin in a patient receiving fluoxetine.  Ann Pharmacother. 1995;29(5):486-488.PubMedGoogle Scholar
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.PubMedGoogle ScholarCrossref
6.
Cone  LA, Sneider  RA, Nazemi  R, Dietrich  EJ.  Mania due to clarithromycin therapy in a patient who was not infected with human immunodeficiency virus.  Clin Infect Dis. 1996;22(3):595-596.PubMedGoogle ScholarCrossref
7.
Finkenbine  R, Gill  HS.  Case of mania due to prednisone-clarithromycin interaction.  Can J Psychiatry. 1997;42(7):778.PubMedGoogle Scholar
8.
Abouesh  A, Hobbs  WR.  Clarithromycin-induced mania.  Am J Psychiatry. 1998;155(11):1626.PubMedGoogle ScholarCrossref
9.
Mermelstein  HT.  Clarithromycin-induced delirium in a general hospital.  Psychosomatics. 1998;39(6):540-542.PubMedGoogle ScholarCrossref
10.
Geiderman  JM.  Central nervous system disturbances following clarithromycin ingestion.  Clin Infect Dis. 1999;29(2):464-465.PubMedGoogle ScholarCrossref
11.
Tse  KC, Li  FK, Tang  S, Lam  MF, Chan  TM, Lai  KN.  Delusion of worm infestation associated with clarithromycin in a patient on peritoneal dialysis.  Perit Dial Int. 2001;21(4):415-416.PubMedGoogle Scholar
12.
Jiménez-Pulido, Navarro-Ruiz  A, Sendra  P, Martínez-Ramírez  M, Garcia-Motos  C, Montesinos-Ros  A.  Hallucinations with therapeutic doses of clarithromycin.  Int J Clin Pharmacol Ther. 2002;40(1):20-22.PubMedGoogle ScholarCrossref
13.
Brooks  JO  III, Hoblyn  JC.  Secondary mania in older adults.  Am J Psychiatry. 2005;162(11):2033-2038.PubMedGoogle ScholarCrossref
14.
Vicente de Vera  C, García  M, Pifarre Teixido  R, Barbe  F.  Delirium induced by clarithromycin in a patient with community-acquired pneumonia.  Eur Respir J. 2006;28(3):671-672.PubMedGoogle ScholarCrossref
15.
Kouvelou  E, Pourzitaki  C, Aroni  F, Papazisis  G, Kouvelas  D.  Acute psychosis induced by clarithromycin in a healthy adult?  J Clin Psychopharmacol. 2008;28(5):579-580.PubMedGoogle ScholarCrossref
16.
Liu  EY, Vasudev  A.  Mania induced by clarithromycin in a geriatric patient taking low-dose prednisone.  Prim Care Companion CNS Disord. 2014;16(3):PCC.14l01626.PubMedGoogle Scholar
17.
Bandettini di Poggio  M, Anfosso  S, Audenino  D, Primavera  A.  Clarithromycin-induced neurotoxicity in adults.  J Clin Neurosci. 2011;18(3):313-318.PubMedGoogle ScholarCrossref
18.
Abouesh  A, Stone  C, Hobbs  WR.  Antimicrobial-induced mania (antibiomania): a review of spontaneous reports.  J Clin Psychopharmacol. 2002;22(1):71-81.PubMedGoogle ScholarCrossref
19.
Gómez-Gil  E, García  F, Pintor  L, Martínez  JA, Mensa  J, de Pablo  J.  Clarithromycin-induced acute psychoses in peptic ulcer disease.  Eur J Clin Microbiol Infect Dis. 1999;18(1):70-71.PubMedGoogle ScholarCrossref
20.
Neff  NE, Kuo  G.  Acute manic psychosis induced by triple therapy for H. pylori.  J Am Board Fam Pract. 2002;15(1):66-68.PubMedGoogle Scholar
21.
Ortíz-Domínguez  A, Berlanga  C, Gutiérrez-Mora  D.  A case of clarithromycin-induced manic episode (antibiomania).  Int J Neuropsychopharmacol. 2004;7(1):99-100.PubMedGoogle ScholarCrossref
22.
Htut  Y, Kunanayagam  S, Poi  PJ.  Clarithromycin induced psychosis.  Med J Malaysia. 2006;61(2):263.PubMedGoogle Scholar
23.
Shah  M, Subhani  M, Rizvon  K, Mustacchia  P.  Transient psychotic episode induced by Helicobacter pylori triple therapy treatment.  Case Rep Gastroenterol. 2012;6(2):381-386.PubMedGoogle ScholarCrossref
24.
Feng  Z, Huang  J, Xu  Y, Zhang  M, Hu  S.  Dissociative disorder induced by clarithromycin combined with rabeprazole in a patient with gastritis.  J Int Med Res. 2013;41(1):239-243.PubMedGoogle ScholarCrossref
25.
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.PubMedGoogle ScholarCrossref
26.
Wong  AY, Root  A, Douglas  IJ,  et al.  Cardiovascular outcomes associated with use of clarithromycin: population based study.  BMJ. 2016;352:h6926.PubMedGoogle ScholarCrossref
27.
HAHO/ITD.  Clinical Data Analysis & Reporting System (CDARS) User's Manual. 2nd ed. Hong Kong: Hospital Authority; 2003:3.
28.
Hospital Authority. Hospital Authority: Introduction. 2015. http://www.ha.org.hk/visitor/ha_visitor_index.asp?Parent_ID=10004&Content_ID=10008&Ver=HTML. Accessed November 25, 2015.
29.
Chan  EW, Lau  WC, Leung  WK,  et al.  Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study.  Gastroenterology. 2015;149(3):586-95.e3.PubMedGoogle ScholarCrossref
30.
Chui  C, Chan  E, Wong  A, Root  A, Douglas  IJ, Wong  IC.  Association between oral fluoroquinolones and seizures: a self-controlled case series study.  Neurology. In press.Google Scholar
31.
Pratt  N, Chan  EW, Choi  NK,  et al.  Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries.  Pharmacoepidemiol Drug Saf. 2015;24(8):858-864.PubMedGoogle ScholarCrossref
32.
Roughead  EE, Chan  EW, Choi  NK,  et al.  Variation in association between thiazolidinediones and heart failure across ethnic groups: retrospective analysis of large healthcare claims databases in six countries.  Drug Saf. 2015;38(9):823-831.PubMedGoogle ScholarCrossref
33.
Whitaker  HJ, Farrington  CP, Spiessens  B, Musonda  P.  Tutorial in biostatistics: the self-controlled case series method.  Stat Med. 2006;25(10):1768-1797.PubMedGoogle ScholarCrossref
34.
Kuriyama  A, Jackson  JL, Doi  A, Kamiya  T.  Metronidazole-induced central nervous system toxicity: a systematic review.  Clin Neuropharmacol. 2011;34(6):241-247.PubMedGoogle ScholarCrossref
35.
Khandheria  M, Snook  E, Thomas  C.  Psychotic episode secondary to metronidazole use.  Gen Hosp Psychiatry. 2014;36(2):231.e3-231.e4.PubMedGoogle ScholarCrossref
36.
Voth  AJ.  Possible association between metronidazole and agitated depression.  Can Med Assoc J. 1969;100(21):1012-1013.PubMedGoogle Scholar
37.
Mahl  TC, Ummadi  S.  Metronidazole and mental confusion.  J Clin Gastroenterol. 2003;36(4):373-374.PubMedGoogle ScholarCrossref
38.
Targum  SD.  Treating psychotic symptoms in elderly patients.  Prim Care Companion J Clin Psychiatry. 2001;3(4):156-163.PubMedGoogle ScholarCrossref
39.
Oliver  DJ.  Hallucinations associated with amoxicillin? a case report.  Practitioner. 1984;228(1396):884.PubMedGoogle Scholar
40.
Stell  IM, Ojo  OA.  Amoxicillin-induced hallucinations: a variant of Hoigne’s syndrome?  Br J Clin Pract. 1996;50(5):279.PubMedGoogle Scholar
41.
Alfonzo  CA, Bobo  WV, Almond  MD.  Not a usual suspect: rabeprazole therapy presenting as a severe neuropsychiatric illness: case report.  Int J Psychiatry Med. 2003;33(3):311-315.PubMedGoogle ScholarCrossref
42.
Hanneken  AM, Babai  N, Thoreson  WB.  Oral proton pump inhibitors disrupt horizontal cell-cone feedback and enhance visual hallucinations in macular degeneration patients.  Invest Ophthalmol Vis Sci. 2013;54(2):1485-1489.PubMedGoogle ScholarCrossref
43.
Akter  S, Hassan  MR, Shahriar  M, Akter  N, Abbas  MG, Bhuiyan  MA.  Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software.  Alzheimers Res Ther. 2015;7(1):79.PubMedGoogle ScholarCrossref
44.
Nau  R, Sörgel  F, Eiffert  H.  Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections.  Clin Microbiol Rev. 2010;23(4):858-883.PubMedGoogle ScholarCrossref
45.
Wallace  RJ  Jr, Brown  BA, Griffith  DE.  Drug intolerance to high-dose clarithromycin among elderly patients.  Diagn Microbiol Infect Dis. 1993;16(3):215-221.PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Overlooking Neuropsychiatric Inherited Real Risk, such a research is fundamentally biased.
    Sergio Stagnaro, Marco Marchionni, Simone Caramel | Quantum Biopysical Semeiotic Research Laboratory
    Unfortunately, not all Authors know till now that the individuals aren't born equal, in the sense that quantum-biophysical semeiotic constitutions really exist, bringing about relative Inherited Real Risk, bedside diagnosed from birth with a common stethoscope, and removed by mitochondrial restructuring quantum Therapy (1, 2). As a matter of facts, neurpsychiatric Inherited Real Risks exist, including that of Alzheimer Disease (3, 4), one of us has discovered formerly and we have described in details in previous papers (3-6). As a consequence, to ascertain the role played of Clarithromicyn in causing neuropsichyatric disorders, Authors have to enroll in the research exclusively individuals involved by the related Inherited Real Risk.

    References.
    1) Caramel S., Marchionni M., Stagnaro S. Morinda citrifolia Plays a Central Role in the Primary Prevention of Mitochondrial-dependent Degenerative Disorders. Asian Pac J Cancer Prev. 2015;16(4):1675. http://www.ncbi.nlm.nih.gov/pubmed/25743850[MEDLINE]
    2) Sergio Stagnaro, Marco Marchionni, Simone Caramel. Early recognition of high risk patients using Biophysical Semeiotics Tests. Neurology, Published October 2, 2014, http://www.neurology.org/content/83/9/776/reply#neurology_el_61750
    3) . Sergio Stagnaro. A fundamental bias of the research: Overlooking Congenital Acidosic Enzyme-Metabolic Histangiopaty-Dependent Brain Inherited Real Risk. Journal of Neurology, Neurosurgery & Psychiatry with practical Neurology, 5 May, 2009. http://jnnp.bmj.com/content/80/11/1206/reply
    4) Marco Marchionni, Simone Caramel, Sergio Stagnaro. Inherited Real Risk of Alzheimer’s Disease: bedside diagnosis and primary prevention.Frontiers in Neuroscience, in http://www.frontiersin.org/Aging_Neuroscience/10.3389/fnagi.2013.00013/full
    5) Marco Marchionni, Simone Caramel, Sergio Stagnaro. The Role of ‘Modified Mediterranean Diet’ and Quantum Therapy In Alzheimer’s Disease Primary Prevention. Letter to the Editor, The Journal of Nutrition, Health & Aging, Volume 18, Number 1, 2014, Springer Ed. http://link.springer.com/article/10.1007/s12603-013-0435-7 [Medline]
    6) Marco Marchionni, Simone Caramel, Sergio Stagnaro. The Auscultatory Percussion of the Stomach Plays a Central Role in Bedside Diagnosis and Primary Prevention of Neurodegenerative Diseases and their Inherited Real Risks. 5th Annual World Congress Neotalk, Nijang, China, http://www.bitlifesciences.com/neurotalk2014/program_path1.asp#p1-2
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    June 2016

    Association Between Acute Neuropsychiatric Events and Helicobacter pylori Therapy Containing Clarithromycin

    Author Affiliations
    • 1Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • 2Research Department of Practice and Policy, School of Pharmacy, University College London, London, England
    • 3Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    • 4Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    JAMA Intern Med. 2016;176(6):828-834. doi:10.1001/jamainternmed.2016.1586
    Abstract

    Importance  There is a concern that Helicobacter pylori therapy containing clarithromycin might be associated with acute neuropsychiatric events.

    Objective  To examine the association between H pylori therapy containing clarithromycin and acute neuropsychiatric events.

    Design, Setting, and Participants  A self-controlled case series study was conducted using the Clinical Data Analysis and Reporting System database in Hong Kong to explore any association. The exposure of interest was H pylori therapy containing clarithromycin in the outpatient setting. Study patients, 18 years or older at cohort entry, must have had both exposure to H pylori therapy containing clarithromycin and their first recorded neuropsychiatric events between January 1, 2003, and December 31, 2012. A post hoc nested case-control analysis was also performed in patients receiving H pylori therapy containing clarithromycin.

    Main Outcomes and Measures  The primary outcome was composite neuropsychiatric events, while secondary outcomes were psychotic events and cognitive impairment. Risk periods in the self-controlled case series analysis were defined as 14-day preexposure period, current use (days 1-14 since prescription start date) and recent use (days 15-30). Age-adjusted incidence rate ratios (IRR) were estimated using the conditional Poisson regression.

    Results  Of 66 559 patients who had at least 1 outpatient prescription of H pylori therapy containing clarithromycin. Their mean (SD) age at cohort entry was 50.8 (14.8 years); their mean age at first exposure was 55.4 (14.8) years, and 30 910 were male (46.4%). A total of 1824 patients had their first recorded composite neuropsychiatric events during the study period. An increased IRR of 4.12 (35 composite neuropsychiatric events during 72 person-years; 95% CI, 2.94-5.76) during current use was observed but not in recent use (9 events during 82 person-years; IRR, 0.95; 95% CI, 0.49-1.83) and 14-day preexposure period (14 events during 72 person-years; IRR, 1.63; 95% CI, 0.96-2.77) vs baseline (1766 events during 16 665 person-years). Similarly, both the risk of psychotic events and cognitive impairment increased during current use vs baseline, although this subsequently returned to baseline incidence levels during recent use. The crude absolute risks of composite neuropsychiatric events, psychotic events, and cognitive impairment during current use were 0.45, 0.12, and 0.12 per 1000 prescriptions, respectively. The nested case-control analysis also gave similar results to that of the self-controlled case series analysis.

    Conclusions and Relevance  This study shows evidence of a short-term increased risk of neuropsychiatric events associated with H pylori therapy containing clarithromycin.

    ×