Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential

ABSTRACT

Introduction: Chronic breathlessness is a common and distressing symptom of advanced disease with few effective treatments. Central nervous system mechanisms are important in respiratory sensation and control. Consequently, drugs which may modify processing and perception of afferent information in the brain may have a role. Antidepressants have been proposed; however, current evidence is limited. Of potentially suitable antidepressants, mirtazapine is an attractive option given its tolerability profile, low cost, and wide availability, along with additional potential benefits.

Areas covered: The paper provides an overview of the physiology of breathlessness, with an emphasis on central mechanisms, particularly the role of fear circuits and the associated neurotransmitters. It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease. The evidence was identified by a literature search performed in PubMed through to October 2018.

Expert opinion: Currently, there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease. Mirtazapine is a promising candidate to pursue, with definitive randomized controlled trials required to determine its efficacy and safety in this setting.

KEYWORDS:

• Chronic lung disease
• chronic breathlessness
• breathlessness perception
• mirtazapine
• antidepressant

Article highlights

• Chronic breathlessness remains a common and distressing symptom of advanced disease with few effective treatment options

• While there is evidence to support the use of parental and oral opioids, not all patients report benefit, and long-term safety data is currently lacking

• Therefore, new effective treatments are urgently needed

• In recent years thinking has moved towards drugs which may modify the processing and perception of afferent information in the brain, such as antidepressants

• Mirtazapine is a promising candidate, but there is currently insufficient evidence to support routine use to treat breathlessness in clinical practice

• Definitive randomized controlled trials are needed to provide evidence to guide clinical practice

Declaration of interest

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 relationships or otherwise to disclose.

Additional information

Funding

This work is independent research funded by Marie Curie, Cicely Saunders International and The Atlantic Philanthropies in the Cicely Saunders Institute Fellowship Programme. N Lovell is completing a training fellowship funded by Cicely Saunders International and Marie Curie [Grant Number A18859]. M Maddocks is supported by an NIHR Career Development Fellowship [CDF-2017-10-009] and NIHR CLARHC South London. IJ Higginson is an NIHR Emeritus Senior Investigator and is supported by NIHR CLARHC South London. This research was supported by the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, which is part of the National Institute for Health Research (NIHR), and is a partnership between King’s Health Partners, St. George’s, University London and St George’s Healthcare NHS Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.