Drug Management – Part 3

Controversies in Fibromyalgia Congress June 2021

Why Opioids should not be used to treat Fibromyalgia
– Mary-Ann Fitzcharles

Published Data Fibromyalgia Patients Who Take Opioids

  • USA internet survey of 2569 FM patients
    • Hydrocodone and acetaminophen taken by 44% of patients
    • Oxycodone and acetaminophen taken by 32% of patients
  • 2/3 had a good effect with opioids

    REF: Bennett RM et al. BMC Musculoskel Disord 2007.
  • German Survey of 1661 FM patients
    • Strong opioids found most harmful
    • Opioids not listed in the top ten preferred treatments
  • REF: Hauser W et al. BMC Musculoskel Disord 2012.

Endogenous Opioid System in FM Patients

Endogenous opioid system = Humans secrete their own internal opioids which work when the opioid chemical attaches to the opioid receptor.

  • This endogenous system is different in FM patients compared to those without FM
    • FM patients have an increased amount of opioids in their CSF (Central Spinal Fluid)
    • FM patients have a decreased number of opioid receptors for an opioid to attach to and have action

Conclusion: Combine these two factors together means;

    • FM patients own system have less opioid receptors so experience more pain
    • Patients with FM will have less pain relief if they take an opioid
    REF: Panerai AE et al. Clin J Pain 2002. Baraniuk JN et al BMC MSK dis 2004.
    Harris RE et al. J Neuroscience 2007. Uceyler N et al. Frontiers Neurosc 2020.

Patient Phenotype and Opioid Consumption

  • Studies indicate the higher the FM score, the higher the neuropathic symptoms (nerve-type pain), the more increased the pain despite opioids suggesting more nociplastic pain (central sensitization).
  • Opioids themselves can cause increase in pain = opioid induced hyperalgesia

  • REF: Brummett CM et al. Aneasthesiology 2013. Janda AM et al. Anaesthes 2015.
             Wasserman RA et al. Pain Medicine 2014.

Canadian Data of Fibromyalgia Patients Taking Opioids

  • In a tertiary care pain clinic in 457 patients, 30% of them took opioids
    • Those taking opioids had
      • Less education and more unemployment
      • More disability, more unstable mental health, more substance abuse and more suicide attempts
  • REF: Fitzcharles M et al. Pain Res Treat 2013.
  • A 12-month prospective study in 1400 FM patients, in which 400 took opioids
    • Those who did not take opioids had
      • Better function, better sleep
      • Less depression, less pain interference
  • REF: Peng X et al. Clin J Pain 2015.

Conclusion: There is little support for long term opioids in management of fibromyalgia.

Why and to what extent do Cannabinoids work in Fibromyalgia Patients? – Silviu Brill

Cannabinoids and Fibromyalgia

  • Fibromyalgia is a prototype of a centralized pain condition
  • FM has been hypothesized to be a “state of deficient endogenous cannabinoids”

Types of Cannabinoids

  • Phytocannabinoids
    • Herbal cannabis, more than 120 active ingredients
  • Endocannabinoids
    • endogenous cannabinoids (naturally produced in humans)
  • Synthetic Cannabinoids
    • Nabilone (Cesamet™), dronabinol (Marinol™), tetranabinex/nabidiolex (Sativex™).

Published Journal Articles on Cannabis in Fibromyalgia Patients

Patient Perspectives on Medical Cannabis

  • USA study of 984 patients taking cannabis from medical cannabis dispensaries
    • >70% effective for all pains
    • BUT there was no record of concentrations, molecules or method of administration
    REF: Piper et al. Pain 2017.
  • USA National Pain Foundation in 1300 FM patients
    • 62% of patients found cannabis very effective
  • REF: US National Pain Foundation survey 2014.


  • Insufficient evidence to recommend any cannabinoid preparation for FM pain.
  • Many studies focus on recreational marijuana rather than medical cannabis.
  • Cannabinoids don’t stop pain so much, rather they cause distraction from pain by altering emotional reactions.

Effect of Different Drugs: Does it make sense in Fibromyalgia? – Winfried Hauser

  • European Medicines Agency that approves drugs and their official indication for use in Europe has not approved the drugs approved for fibromyalgia in Canada (pregabalin, duloxetine) or approved in the United States (pregabalin, duloxetine, milnacipran).

Evidence of Combination of Drugs in Fibromyalgia

16 studies reviewed with a total of 1474 patients

  • 3 studies (306 patients) combined an NSAID (non-steroidal Anti-inflammatory) + benzodiazepine
  • 2 studies (89 patients) combined amitriptyline + fluoxetine
  • 2 studies (92 patients) combined amitriptyline + another drug
  • 2 studies (164 patients) combined melatonin + antidepressant
  • 1 study (58 patients) combined carisoprodol + acetaminophen + caffeine
  • 1 study (315 patients) combined tramadol + acetaminophen
  • 1 study (24 patients) combined malic acid + magnesium
  • 1 study (200 patients) combined a monoamine oxidase inhibitor + 5-hydroxytryptophan (5-HT)
  • 1 study (41 patients) combined pregabalin + duloxetine

  • REF: Cochrane Database Syst Rev. 2018 Feb 19;2(2):CD010585.

A Tailored Approach to Drug Management of Fibromyalgia

  • Based on Key Symptoms and Comorbidities
    • If sleep disturbances use amitriptyline or pregabalin
    • If depression use duloxetine
    • If generalized anxiety disorders use duloxetine and pregabalin
  • Based on Warnings and Contraindications
    • If liver disease avoid SNRIs
    • If a professional driver avoid pregabalin (note: in Germany you lose your job if taking pregabalin and you drive for a living)
  • Based on Patient Preferences
    • Stop if weight gain with amitriptyline or pregabalin use
  • Use of third and fourth-line drugs
    • If sleep problems try cannabis or cyclobenzaprine or quetiapine
    • If depression try SSRIs
    • If severe depression try quetiapine

Multicomponent Treatment Strategies in Fibromyalgia – Jacob Ablin

  • Drug management requires careful and meticulous titration needing frequent check-ins with the patient to be able to finetune treatment to increase compliance and minimize side effects.
  • Each patient with fibromyalgia is unique and requires a customized management plan.
  • FM patients have limited energy and resources to spend on multiple therapeutic programs
  • The management program must be simple and doable

Reported by Janice Sumpton October 29, 2021