A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia.

Kim Lawson

doi:10.3390/biomedicines5020024

Abstract

Fibromyalgia is a complex chronic condition characterized by pain, physical fatigue, sleep disorder and cognitive impairment. Evidence-based guidelines recommend antidepressants as treatments of fibromyalgia where tricyclics are often considered to have the greatest efficacy, with amitriptyline often being a first-line treatment. Amitriptyline evokes a preferential reduction in pain and fatigue of fibromyalgia, and in the Fibromyalgia Impact Questionnaire (FIQ) score, which is a quality of life assessment. The multimodal profile of the mechanisms of action of amitriptyline include monoamine reuptake inhibition, receptor modulation and ion channel modulation. Several of the actions of amitriptyline on multiple nociceptive and sensory processes at central and peripheral locations have the potential to act cumulatively to suppress the characteristic symptoms of fibromyalgia. Greater understanding of the role of these mechanisms of action of amitriptyline could provide further clues to the pathophysiology of fibromyalgia and to a preferable pharmacological profile for future drug development.

Highlights

Fibromyalgia is a complex chronic condition characterized by widespread pain, physical fatigue, non-restorative sleep and cognitive impairment [1,2]
Amplified responses of the central nervous system (CNS) to peripheral sensory input leading to enhanced neuronal excitability and central sensitization have been reported to be associated with hyperalgesia and allodynia, which are symptoms characteristic of fibromyalgia [1]
This review will focus on the pharmacology of amitriptyline that could be responsible for the benefits observed in the treatment of fibromyalgia

Summary

Introduction

Fibromyalgia is a complex chronic condition characterized by widespread pain, physical fatigue, non-restorative sleep and cognitive impairment [1,2]. Antidepressants act on noradrenergic and serotonergic neurons, which are implicated in the mediation of endogenous pain inhibitory mechanisms and associated with several aspects of the pathophysiology. Descending serotonergic-noradrenergic and opioidergic efferent pathways, which form the diffuse noxious inhibitory control (DNIC), are activated in healthy subjects by the application of intense painful stimuli leading to downregulation of the pain signal. The DNIC has been reported to be reduced or absent [9]. Consistent with decreased endogenous serotonergic and noradrenergic activity and a reduced DNIC in patients with fibromyalgia is an altered biochemistry of serotonin and noradrenaline. Lower levels of main metabolites of serotonin and noradrenaline, 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenethylene glycol (MHPG) respectively, in cerebrospinal fluid and of L-tryptophan and serotonin in blood are observed in patients with fibromyalgia compared to healthy controls [1,8]. This review will focus on the pharmacology of amitriptyline that could be responsible for the benefits observed in the treatment of fibromyalgia

Pharmacology of Antidepressants and Fibromyalgia

10 VLD 1–4

Pharmacology of Amitriptyline and Fibromyalgia

Findings

Conclusions