Skip to main content
×
×
Home

Association of autonomic dysfunction and clozapine: Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication

  • Hagit Cohen (a1), Uri Loewenthal (a1), Michael Matar (a1) and Moshe Kotler (a1)
Abstract
Background

Antipsychotic medications cause a wide range of adverse effects and have been associated with sudden death in psychiatric patients.

Aims

To supply power spectral analysis of heart rate variability as a tool to examine the arrythmogenic effects of neuroleptics.

Method

Heart rate analysis was carried out in patients with schizophrenia on standard doses of neuroleptic monotherapy − 21 were on clozapine, 18 on haloperidol and 17 on olanzapine – and in 53 healthy subjects.

Results

Patients with schizophrenia on clozapine had significantly higher heart rate, lower heart rate variability and lower high-frequency and higher low-frequency components compared with patients on haloperidol or olanzapine and matched control subjects. Prolonged QTc intervals were more common in patients than controls.

Conclusions

Patients treated with neuroleptic medications, especially clozapine, showed autonomic dysregulation and cardiac repolarisation changes. Physicians should be aware of this adverse reaction.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Association of autonomic dysfunction and clozapine
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Association of autonomic dysfunction and clozapine
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Association of autonomic dysfunction and clozapine
      Available formats
      ×
Copyright
Corresponding author
Hagit Cohen, Anxiety and Stress Research Unit, Ministry of Health Mental Health Center, Faculty of Health-Sciences, Ben-Gurion University of the Negev, PO Box 4600, Beer-Sheva, Israel. Fax: 972-8-6401742; e-mail: hagitc@bgumail.bgu.ac.il
Footnotes
Hide All

Declaration of interest

None.

Footnotes
References
Hide All
Akselrod, S., Gordon, D., Ubel, F., et al (1981) Power spectral analysis of heart rate fluctuation: a quantitative probe of beat-to beat cardiovascular control. Science, 213, 220222.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washington, DC: APA.
Anon. (1966) Sudden death and phenothiazines. Lancet, ii, 740.
Appleby, L., Thomas, S., Ferrier, N., et al (2000) Sudden unexplained death in psychiatric in-patients. British Journal of Psychiatry, 176, 405406.
Barnett, A. (1996) Safety concerns over antipsychotic drug: sertindole. Lancet, 348, 256.
Chute, D., Grove, C., Rajasekhara, B., et al (1999) Schizophrenia and sudden death: a medical examiner case study. American Journal of Forensic Medical Pathology, 20, 131135.
Drici, M. D., Wang, W. X., Liu, X. K., et al (1998) Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. Journal of Clinical Psychopharmacology, 18, 477481.
Endicott, J. & Spitzer, R. L. (1987) Schedule for Affective Disorders and Schizophrenia (SADS). Acta Psychiatrica Belgica, 87, 361516.
Jacobs, B. (1987) Central Monoaminergic Neurons: Single-Unit Studies in Behaving Animals. New York: Raven Press.
January, C. T., Riddle, J. M. & Salata, J. J. (1988) A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644. Circulation Research, 62, 563571.
Lader, M. (1999) Some adverse effects of antipsychotics: prevention and treatment. Journal of Clinical Psychiatry, 60 (suppl. 12), 1821.
Rechlin, T., Beck, G., Weis, M., et al (1998) Correlation between plasma clozapine concentration and heart rate variability in schizophrenic patients. Psychopharmacology (Berlin) 135, 338341.
Reilly, J. G., Ayis, S. A., Ferrier, I. N., et al (2000) QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet, 355, 10481052.
Roden, D. M., Lazzara, R., Rosen, M., et al (1996) Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS. Circulation, 94, 19962012.
Ruschena, D., Mullen, P. E., Burgess, P., et al (1998) Sudden death in psychiatric patients. British Journal of Psychiatry, 172, 331336.
Shiloh, R., Nutt, D. & Weizman, A. (1999) Atlas of Psychiatric Pharmacotherapy (1st edn). London: Martin Dunitz.
Suttmann, I., Ditter, S., Landgraf, R., et al (2000) Clozapine and sudden death. Lancet, 355, 842843.
Task Force (1988) Sudden Death in Psychiatry Patients: the Role of Neuroleptic Drugs. Washington, DC: American Psychiatric Association.
Task Force (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. European Heart Journal, 17, 354381.
Viskin, S. (1999) Long QT syndromes and torsade de pointes. Lancet, 354, 16251633.
Zahn, T. P. & Pickar, D. (1993) Autonomic effects of clozapine in schizophrenia: comparison with placebo and fluphenazine. Biological Psychiatry, 34, 312.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 22 *
Loading metrics...

Abstract views

Total abstract views: 85 *
Loading metrics...

* Views captured on Cambridge Core between 2nd January 2018 - 18th June 2018. This data will be updated every 24 hours.

Association of autonomic dysfunction and clozapine: Heart rate variability and risk for sudden death in patients with schizophrenia on long-term psychotropic medication

  • Hagit Cohen (a1), Uri Loewenthal (a1), Michael Matar (a1) and Moshe Kotler (a1)
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *