Trazodone: properties and utility in multiple disorders

Abstract

Trazodone is an established antidepressant that is prescribed frequently as an off-label hypnotic with wide acceptance among psychiatrists. Owing to its atypical mixed serotonergic and adrenolytic pharmacology, trazodone has been investigated in a number of disorders besides depression and insomnia, including anxiety disorders, chronic pain, frontal cognitive dysfunctions, erectile dysfunction and others. Clinical studies using subjective and objective measures generally tend to support its efficacy as a hypnotic in depressed subjects. Various other attributes of trazodone, including interaction with adrenergic receptors, formation of an active metabolite with potent serotonergic activity, low abuse potential and putative utility in various disorders, warrant further exploration. The adverse effects of trazodone generally mirror its serotonergic activity and include sedation, headache, sweating, weight changes and gastrointestinal effects such as nausea and vomiting. Clinicians and patients should be cognizant of the risk for potential, but rare, cardiovascular adverse effects of trazodone. The safety and toxicology of trazodone should be examined under current standards of drug development before exposure to new patient populations. This article provides an overview of trazodone with a focus on its clinical pharmacology and opportunities, gaps and scientific strategies in developing it for new indications such as insomnia, anxiety disorders, chronic pain and frontal cognitive dysfunction. Modified release formulations, alternate forms of drug delivery and combination products are discussed as strategies to optimize the efficacy of trazodone and improve its safety profile.

Keywords::

• anxiety
• chronic pain
• cognitive dysfunction
• drug delivery
• first-pass metabolism
• insomnia
• m-CPP
• optimization
• repurpose

Acknowledgement

The author would like to thank colleagues at IMPAX and external physicians for stimulating discussions.

Financial & competing interests disclosure

The author is an employee of IMPAX Pharmaceuticals, a division of IMPAX Laboratories. The author has 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.

No writing assistance was utilized in the production of this manuscript.