A comprehensive review of swallowing difficulties and dysphagia associated with antipsychotics in adults

ABSTRACT

Introduction

This is a comprehensive review of antipsychotic (AP)-induced dysphagia and its complications: choking and pneumonia.

Areas covered

Four PubMed searches were completed in 2018. The limited literature includes: 1) 45 case reports of AP-induced dysphagia with pharmacological mechanisms, 2) a systematic review of APs as a risk factor for dysphagia, 3) reviews suggesting adult patients with intellectual disability (ID) and dementia are prone to dysphagia (APs are a risk factor among multiple others), 4) studies of the increased risk of choking in patients with mental illness (APs are a contributing factor), 5) naturalistic pneumonia studies suggesting that pneumonia may contribute to AP-increased death in dementia, and 6) naturalistic studies suggesting that pneumonia may be a major cause of morbidity and mortality in clozapine patients.

Expert commentary

The 2005 Food and Drug Administration requirement that package inserts warn of AP-induced dysphagia jumpstarted this area, but current studies are limited by: 1) its naturalistic nature, 2) the lack of dysphagia studies of patients with IDs and dementia on APs, and 3) the assumed indirect association between dysphagia with choking and pneumonia. Future clozapine studies on pneumonia, if they lead to a package insert warning, may have high potential to save lives.

KEYWORDS:

• Airway obstruction/chemically induced
• antipsychotic agents/adverse effects
• deglutition/physiology
• deglutition disorders/chemically induced
• respiratory aspiration
• pneumonia
• aspiration

Article highlights

• Antipsychotic (AP)-induced dysphagia and swallowing difficulties have been described since the introduction of APs, but were neglected until the Food and Drug Administration (FDA) required a warning in the package insert in 2005.

• Dysphagia can be classified based on location as oral/pharyngeal phase or esophageal phase. It can lead to complications such as choking and aspiration pneumonia.

• Among adult psychiatric patients, patients with intellectual disability (ID) and dementia appear particularly prone to dysphagia and its complications, but they have not been well studied. APs are probably only one risk factor for dysphagia among multiple others.

• APs can affect swallowing, particularly the oral and pharyngeal phases. Table 1 summarizes the neurotransmitter abnormalities presumably involved in AP-induced swallowing difficulties.

• In 45 cases of dysphagia caused by APs: roughly ¼ of the cases were explained by 1) parkinsonism, 2) acute dystonic reactions, 3) sialorrhea and 4) tardive dyskinesia. Sedation and xerostomy appeared important in a very few cases.

• Choking and, more importantly, choking deaths appear to be more frequent in adults with mental illness than in the general population; APs may possibly be a risk factor for choking.

• After 2005, further naturalistic studies have verified that, in effect, APs can increase mortality in patients with dementia and that pneumonia, possibly aspiration pneumonia, is an important mechanism explaining increased deaths.

• Clinicians need to remember: 1) clozapine is prone to cause dysphagia (due to sialorrhea and sedation); 2) secondarily, this can lead to aspiration pneumonia; and 3) once aspiration pneumonia develops, this acts as a drug interaction that increases clozapine levels, further complicating the picture. Furthermore, naturalistic studies in several countries, using different designs, are starting to provide hints that pneumonia may be a major cause of morbidity and mortality in clozapine patients. Newer, larger, and better clozapine studies on pneumonia, particularly if they lead to a package insert warning, may have high potential to save lives.

Acknowledgments

The authors are grateful to the reviewers for providing useful suggestions for improving the article. The authors acknowledge Lorraine Maw, M.A., from the University of Kentucky Mental Health Research Center at Eastern State Hospital, who helped in editing the article. Dr. de Leon is grateful to the Mortality Review Committee, which reviews deaths in psychiatric facilities in Kentucky, and all the members of this Committee who have helped him since 2002 to acquire extensive knowledge of the deaths among inpatient and outpatient psychiatric patients, including deaths by choking, aspiration and aspiration pneumonia.

Declaration of interest

In the past few years, E Spina has participated in speakers/advisory boards and lectured, supported by Arcapharma, Angelini, Janssen Pharmaceuticals, Lundbeck, Otsuka and Recordati. J de Leon personally develops his presentations for lecturing, has never lectured using any pharmaceutical or pharmacogenetic company presentations, and has never been a consultant for pharmacogenetic or pharmaceutical companies. In the past, J de Leon received researcher-initiated grants from Eli Lilly (one ended in 2003 and the other, as co-investigator, ended in 2007); from Roche Molecular Systems, Inc. (ended in 2007); and, in a collaboration with Genomas, Inc., from the NIH Small Business Innovation Research program (ended in 2010). J de Leon has been on the advisory boards of Bristol-Myers Squibb (2003/04) and AstraZeneca (2003). Roche Molecular Systems supported one of his educational presentations, which was published in a peer-reviewed journal (2005). His lectures were supported once by Sandoz (1997), twice by Lundbeck (1999 and 1999), twice by Pfizer (2001 and 2001), three times by Eli Lilly (2003, 2006, and 2006), twice by Janssen (2000 and 2006), once by Bristol-Myers Squibb (2006), and seven times by Roche Molecular Systems, Inc. (once in 2005 and six times in 2006). No commercial organizations had any role in the writing of this paper for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.