Emerging pharmacological strategies for the treatment of fibromyalgia

Table 1 Currently recommended drugs for the management of fibromyalgia[9,30,31]

Drug	Mechanism of action	Symptom improved
Amitriptyline	Tricyclic antidepressant	Pain, sleep, fatigue
Cyclobenzaprine	Tricyclic antidepressant	Sleep
Duloxetine	Serotonin-noradrenaline reuptake inhibitor	Pain, sleep
Milnacipran	Serotonin-noradrenaline reuptake inhibitor	Pain, fatigue
Pregabalin	α2δ ligand	Pain, sleep, fatigue
Tramadol	Weak opioid and serotonin-noradrenaline reuptake inhibitor	Pain

Table 2 Emerging drug therapies with potential efficacy for the treatment of fibromyalgia

Drug	Mechanism of action	Regime	Effect on pain	Secondary domains accessed		Trial sponsor	Ref.
			VAS-P	Significantly improved	No observed effect
Agomelatine	Melatoninergic receptor agonist and 5-HT2 receptor antagonist	25 mg/d during 12 wk	-1.06 (5.13 - 4.07)	FIQ, anxiety, depression,	Sleep disorder, cognitive/executive function, quality of life index	University of Messina	[34]
		25-50 mg/d during 12 wk					[35]
Capsaicin	Transient receptor potential vanilloid 1 subunits	Topical 0.075% TID during 6 wk	No significant effect	FIQ (-9.81), fatigue severity, depression, myalgic score, pressure pain threshold	Anxiety, physical functioning	Rheumatology Service at the Specialist Clinic of Cantabria	[36]
Dronabinol (delta-9-tetrahydrocannabinol)	Cannabinol	Daily dose 2.5 -15 mg during 7 mo	-3.5 (7.9-4.4)	Anxiety, depression, quality of life		Heidelberg University	[37]
Droxidopa	Noradrenaline prodrug	600 mg TID during 9 wk	-1.64 (cf pl -0.74)	FIQ (-9.72)		Chelsea Therapeutics/Lundbeck	[38]
Esreboxetine	Noradrenaline reuptake inhibitor	4/8/10 mg/d during 14 wk	-1.55 - 1.85 (cf pl -0.42 - -0.76)	FIQ (-3.88 to -7.12), PGIC score, GFI score (-0.30 to -0.64)	SF-36 physical function score	Pfizer	[39]
IMC-1 Celecoxib + famciclovir	Viral suppression of herpes virus	Fixed dose combination during 16 wk	-1.9	FIQ (-17.5), PGIC, fatigue		Innovative Med Concepts	[40]
Melatonin	Endogenous melatonin receptor ligand	10 mg/d during 6 wk	-1.74 (6.49-4.75)	FIQ (-17.7), sleep, tender points		Brazilian Committee for Development of Higher Education Personnel and National Council for Scientific and Technological Development	[41]
		10 mg/d plus 25 mg/d amitriptyline during 6 wk	-2.1 (6.96-4.86)	FIQ (-24.7), sleep, tender points
Memantine	NMDA antagonist	20 mg/d during 5 mo	-1.9 (cf pl -3.1) (6.9-5.0)	FIQ (-13.2), CGI, Quality of life score,	Cognitive state, depression	Aragon Institute of Health Sciences	[42]
Mirtazapine (Org 3770)	a2 adrenergic and 5-HT2 and 5-HT3 receptor antagonist	15 mg/d during 1 wk then 30 mg/d during 12 wk	-1.6 (cf pl -0.4)	FIQ (-12.9), anxiety, depression, PGIC, quality of life		Meiji Seika Pharma Co., Ltd.	[43,44]
Nabilone	Cannabinoid receptor agonist	0.5-1.0 mg during 4 wk	-2.04 (cf pl -1.43)	FIQ (-12.07), anxiety		University of Manitoba	[45]
		0.5-1.0 mg during 2 wk	No effect	Sleep	Pain, mood, quality of life	Winnipeg Regional Health Authority	[46]
Naltrexone	Opioid receptor antagonist	4.5 mg/d during 12 wk	-1.55 (cf pl -0.43)	Mood	Sleep, fatigue	Stanford University	[47]
Pramipexole	Dopamine agonist	4.5 mg/d during 14 wk	-2.48 (cf pl -1.77)	FIQ (-9.57), physical function, fatigue	Mood, depression, anxiety, tender point score		[48]
TD-9855	Noradrenaline serotonin reuptake inhibitor	20 mg/d during 6 wk	-1.4 (cf pl -0.5)	FIQ (-16.2), PGIC, global and cognitive fatigue		Theravance Biopharm	[49]
TNX102SL cyclobenzaprine	Noradrenaline, serotonin reuptake inhibition, adrenergic and serotonin receptor antagonist	1-4 mg/d during 8 wk	-0.6 (cf pl -0.6)	Fatigue, tenderness, sleep, depression		Tonix Pharmaceuticals	[50,51]
Trazodone	5-HT receptor antagonist and serotonin reuptake inhibitor	50-300 mg/d during 12 wk then trazodone/pregabalin (max 450 mg/d) during 12 wk	-0.45	FIQ (-10), fatigue, stiffness, anxiety, depression, PGI		Universidad de Granada	[52]
			-1.29	FIQ (-13.4)

CGI: Clinical Global Impressions; FIQ: Fibromyalgia impact questionnaire; GFI: Global fatigue index; PGI: Patient global improvement; PGIC: Patient’s global impression of change; SF-36: 36-item short form health survey; cf pl: Compared with placebo; TID: 3 times daily; VAS-P: Visual Analog Scale of Pain based on a 0-10 scale.

Table 3 Novel drugs in clinical trials for potential treatment of fibromyalgia

Drug	Mechanisms of action	Domains	Trial Sponsor	Ref.
EMA401	Angiotensin 2 receptor antagonist	Pain	Novartis/Spiniflex	[53]
Flupirtine	Potassium channel activation	Pain	Not available	[54]
Mirogabalin (DS-5565)	α2δ ligand	Pain	Daiichi Sankyo	[55]
Suvorexant	Orexin receptor antagonist	Sleep, insomnia, pain	Henry Ford Health System	[56]
Yokukansan	Herbal medication; glutamatergic and serotonergic systems	Insomnia, sleep	St Marianna University, school of Medicine	[57]
ZYN001	Cannabinoid	Pain, quality of life	Zynerba	[58]

Sources of information, MEDLINE (PubMed), ClinicalTrials.gov, adisinsight.springer.com and Controlled-trials.com.