Stroke risk in elderly treated with antipsychotics is newly linked to specific drug actions

Reports new study in Biological Psychiatry

2013-03-11

(Press-News.org) Philadelphia, PA, March 11, 2013 – Antipsychotic administration in the elderly is associated with an increased risk for cerebrovascular accident, more commonly known as stroke; a new study published in Biological Psychiatry provides additional insight into this important relationship.

Antipsychotics are prescribed to elderly patients to treat symptoms such as agitation, psychosis, anxiety, insomnia, and depression. The increased risk of stroke associated with these medications was identified approximately a decade ago and has since been replicated by subsequent studies. Although the increase in stroke risk is small, some guidelines discourage the prescription of antipsychotics to elderly patients.

Antipsychotic drugs vary in their effects on the body and so it is likely that antipsychotics are not uniform in their effects on stroke risk. Thus, better understanding of the mechanisms through which antipsychotics increase stroke risk might guide the prescription of safer drugs for elderly patients.

In their study, Wu and colleagues focused on the wide range of brain mechanisms targeted by antipsychotic medications. All antipsychotics block the D2 subtype of receptor for the neurotransmitter dopamine. However, these drugs also act on a range of other receptor targets including the serotonin 5-HT2 receptor, the M1 receptor for the transmitter acetylcholine, and the alpha2 receptor for noradrenaline.

To conduct the study, the researchers matched information from a large national database of insurance claims to what is known about the receptor binding profiles of the antipsychotic drugs.

"We found that antipsychotics with a high binding affinity of alpha2 adrenergic and M1 muscarinic receptors were associated with a greater risk of stroke than the use of other types of antipsychotics," said Dr. Susan Shur-Fen Gau, Professor and Chair at National Taiwan University and corresponding author of the study.

They also found that this stroke risk was elevated in patients who were older and had dementia. Stroke risk was also related to duration and dosage of treatment, with patients who received either short duration of antipsychotic treatment (4 weeks or less) or higher daily doses of treatment showing an increased risk of stroke. This suggests that risk is highest in the initial weeks of antipsychotic treatment and for those with a higher average daily dose.

"Antipsychotics have a wide range of receptor profiles. The stroke risk profiles from this study suggest that it may be possible to use antipsychotics more safely in the elderly," commented Dr. John Krystal, Editor of Biological Psychiatry.

Additional research is necessary, but the authors agree. They recommend that clinicians start antipsychotics at low dosages and closely monitoring for side effects in the initial treatment, particularly for individuals with older age and the presence of dementia.

### The article is "Association of Stroke with the Receptor-Binding Profiles of Antipsychotics—A Case-Crossover Study" by Chi-Shin Wu, Sheng-Chang Wang, Susan Shur-Fen Gau, Hui-Ju Tsai, and Yu-Cheng Cheng (doi: 10.1016/j.biopsych.2012.07.006). The article appears in Biological Psychiatry, Volume 73, Issue 5 (March 1, 2013), published by Elsevier.

Notes for Editors Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Susan Shur-Fen Gau at +886 2 23123456 ext 66802 or gaushufe@ntu.edu.tw.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 5th out of 129 Psychiatry titles and 16th out of 243 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2011 Impact Factor score for Biological Psychiatry is 8.283.

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Stroke risk in elderly treated with antipsychotics is newly linked to specific drug actions

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