Fibromyalgia is a disorder which is characterized by chronic pain. An extensive number of studies are being conducted in the present era to find new medicines or develop techniques that can help combat fibromyalgia. It is these researches and their findings that form the subject matter of this discussion.
Milnacipran therapy for up to one year is tolerable and successful in adult patients with FM in clinical trials. Pain relief was seen in some patients as early as week one of care, and pain relief was maintained during the 15-week, 20-27-week, 19, and 6-month extension studies23 (one-year total). Milnacipran is also not generally associated with sedation, cognitive decline, or weight gain, according to clinical trial findings, and it has no detrimental effects on sleep. Milnacipran is unlikely to worsen typical FM symptoms like fatigue, weight gain, or somnolence, based on this safety profile.
Tricyclic Antidepressants (TCAs)
While different TCAs have been used to treat chronic pain, amitriptyline has the largest body of evidence on therapeutic utility in FMS. All the clinical practice recommendations recommend it. Amitriptyline was found to minimize FIQ questionnaire results by over 30% from baseline to endpoint. It has been shown to help with pain, exhaustion, sleep, and overall quality of life. Antidepressant drugs are known as selective serotonin reuptake inhibitors (SSRIs). They influence the levels of brain chemicals that control emotions and pain. Duloxetine (Cymbalta), Milnacipran (Savella), and venlafaxine are SNRIs used to treat fibromyalgia (Effexor XR).
Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs)
Several clinical trials testing duloxetine found that it substantially decreased FMS-related pain and depressive symptoms. Milnacipran has demonstrated a substantial improvement in pain levels as well as fatigue in most clinical trials. The increase in psychological effects of FMS (specifically, depression) is less certain. A meta-analysis of five studies on duloxetine and five studies on milnacipran found that both medications were effective in reducing pain and enhancing patient expectations of clinical progress.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Citalopram, escitalopram, fluoxetine, paroxetine, and sertraline were among the SSRIs studied for the treatment of FMS. Despite the theoretical assumption that combined serotonin and noradrenaline inhibition is more effective than selective serotonin augmentation for pain inhibition, practice guidelines recommend the use of this class of drugs. SSRIs boost pain, depression, and overall quality of life, but only to a limited degree, according to the findings of a meta-analysis conducted by Häuser et al. The impact size for sleep disorder improvement was found to be insignificant.
Cyclobenzaprine is a 5-HT2 receptor antagonist that relaxes muscles by acting on a subfamily of serotonin receptors. It has a structure like amitriptyline and is widely administered to FMS patients. According to a systematic review of the literature, it has a moderate benefit in improving sleep problems but only a minor benefit in pain relief. Moldofsky et al. previously demonstrated that bedtime very low doses of cyclobenzaprine improved pain and sleep in patients with complex sleep architecture. In FMS patients, a sublingual formulation of low-dose cyclobenzaprine (TNX-102SL, 2.8 mg) was found to enhance nonrestorative sleep.
Mirtazapine is an atypical antidepressant that acts on the noradrenergic and serotonergic systems. It is not allowed to be used in FMS. Welsch et al. found the medication ineffective for pain relief in FMS or any other associated mental or functional symptoms (depression, sleep disorders, exhaustion, etc.) in a meta-analysis.
Pregabalin and gabapentin, the two key members of this family of drugs, function by binding to the alpha2delta subunit of voltage-gated calcium channels in the CNS. They were initially used as anticonvulsants but are now mostly used to treat chronic pain. The use of pregabalin for the treatment of FMS has been approved by the FDA, and it is recommended in guidelines.
Pregabalin reduced pain and sleep disturbances in a series of placebo-controlled clinical trials. However, it was not found to substantially boost fatigue problems in any trials as compared to placebo, and none of the trials showed an increase in depressive symptoms.
FMS is thought to minimize endogenous descending antinociceptive activity. The noradrenaline/serotonin-mediated pathway and the opioid-mediated pathway are two descending pain inhibitory pathways that exist in humans. In FMS, Baraniuk et al. proposed an excess of endogenous opioids. Apart from its opioid receptor antagonist properties, naltrexone also has antagonist properties for nonopioid receptors (toll-like receptor 4) expressed on activated microglial cells, a type of macrophage that plays a role in neuroinflammatory processes. Researchers and clinicians will be able to use microglial activation as a biomarker for FMS activity and to calculate the impact of naltrexone due to the ability to quantify it using nuclear methods.
Dopamine Receptor Agonists
Evidence that dopaminergic pathways are involved in the pathophysiology of FMS has led to attempts to develop drugs that interfere with dopaminergic metabolism. With most evidence for the benefit of dopaminergic agonists being intermittent, it’s worth considering terguride, which was found to enhance FMS symptoms in a subgroup of patients with spinal stenosis in a randomized, double-blind placebo-controlled study (as compared to comparing all terguride-assigned patients to the placebo group, where no significant improvement was found. Even though the EULAR guidelines for FMS management from 2008 recommended that dopamine agonists be considered, a meta-analysis performed by Sommer et al. found them to be of no known benefit, and therefore they are not included in the updated 2016 EULAR recommendations.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two main active ingredients in cannabinoids (CBD). The former is the psychoactive portion, which acts through CB1 and CB2 receptors to cause pain (as well as emotions). The latter has analgesic and anti-inflammatory effects. As a result, the THC: CBD ratio specifies the overall effect of the substance. CB1 cannabinoid receptors are primarily located in the central nervous system and peripheral nervous system. Their agonists act as pain modulators along sensory pathways. In terms of the endocannabinoid system’s complex role in pain control, FMS is thought to be triggered, among other things, by a lack of endocannabinoid activity.