Effects of Antidepressant Mirtazapine on Fibromyalgia Symptoms

by M G Rana, MD.

Fibromyalgia is a heterogenous condition

The definite aetiology (cause) of this syndrome remains unknown. A model of interacting biological and psychosocial variables in the predisposition, triggering, and development of the chronicity of fibromyalgia symptoms has been suggested.

Several factors are associated with the pathophysiology (functional changes associated with or resulting from disease) of fibromyalgia, but the precise relationship to symptoms of the disorder are unclear. The best established pathophysiological features are those of central sensitisation; i.e. augmented pain and sensory processing in the brain, with increased functional connectivity to pro-nociceptive brain regions and decreased connectivity to antinociceptive regions, and accompanying changes in central nervous system (CNS) neurotransmitters as well as the size and shape of brain regions.

What is Mirtazapine?

Mirtazapine promotes the release of noradrenaline and serotonin by blocking α2-adrenergic autoreceptors and α2-adrenergic heteroreceptors, respectively. It also enhances serotonin neurotransmission, mainly through 5-HT1A receptors, and blocking postsynaptic 5-HT2A, 5-HT2C, and 5-HT3 receptors.

Based on these pharmacological mechanisms, mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant. Because mirtazapine increases the extracellular levels of noradrenaline and serotonin (an effect similar to serotonin–noradrenaline reuptake inhibitors and tricyclic antidepressants, albeit via different mechanisms), mirtazapine is expected to have analgesic effects and improve sleep disturbances in patients with FM.

 

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A systematic review

Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in patients with fibromyalgia. The objective of this systematic review is to assess the efficacy and safety of mirtazapine in the treatment of patients with fibromyalgia.

CENTRAL and ClinicalTrials.gov were queried using the search term combination: fibromyalgia, pain, chronic pain, neuralgia, neuropathic pain, chronic widespread pain, or chronic pain syndrome and mirtazapine. Studies appropriate to the objective were evaluated, including three randomized, placebo-controlled trials and one open-label trial, investigating the effect of mirtazapine in patients with fibromyalgia.

In patients with fibromyalgia, treatment with mirtazapine resulted in improvements in pain, sleep, and quality of life. Study durations ranged from 6 to 13 weeks and studies used varying dosing strategies for mirtazapine. Minor occurrences of somnolence, weight gain, nasopharyngitis, dry mouth, and increased appetite were reported with mirtazapine use.

Based on the reviewed literature, mirtazapine appears to be a promising therapy to improve pain, sleep, and quality of life in patients with fibromyalgia. These benefits were demonstrated in patients that were treatment naïve and those that had failed previous therapies. Additional clinical evidence through larger and longer length trials would be of benefit to further define the role of mirtazapine for patients with fibromyalgia.

It is an additional pharmacological therapeutic option

The serotonin-norepinephrine reuptake inhibitor antidepressants duloxetine and milnacipran have been approved by the Food and Drug Administration (FDA), but not by the European Medicines Agency (EMA) for fibromyalgia. Both drugs increase the availability of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine at CNS synaptic clefts.

They have the potential to reduce pain by correcting the functional deficit of 5-HT and norepinephrine neurotransmission in the descending inhibitory pain pathway. These antidepressants are effective in relieving one key symptom of fibromyalgia, namely pain, but do not reduce sleep problems to a clinically-relevant degree. There is a need for additional pharmacological therapeutic options for the treatment of the key fibromyalgia symptoms pain, sleep problems and fatigue.

Mirtazapine (Remeron) as a potential treatment in treating fibromyalgia pain

The study focused on the drug mirtazapine (Remeron) as a potential treatment in treating fibromyalgia pain. Currently mirtazapine is prescribed as an antidepressant, but the study showed that it did provide a noticeable decrease in pain for fibromyalgia patients that were not suffering from depression.

Previous studies on mirtazapine for fibromyalgia treatment demonstrated the drug could be useful in treating not just the pain fibromyalgia causes, but also other fibro symptoms, such as sleep disturbances and fatigue. Researchers have found that mirtazapine acts in a similar way to an already approved fibromyalgia treatment, duloxetine (a serotonin-noradrenaline reuptake inhibitor).

Purposes of this most recent study

The purposes of this most recent study into mirtazapine were to test the effectiveness of the drug as a fibromyalgia treatment at a fixed dosage. In order to eliminate conflicting results, the study chose to avoid using patients that showed signs of depression as mirtazapine are an antidepressant and this could cause potential bias.

Conducted over a period of 12 weeks, the study involved 430 patients suffering from fibromyalgia. The patients were divided into two groups, with half the patients receiving a daily dose of mirtazapine of 15 mg through the first week and 30 mg for the remaining 11 weeks.

The other half was administered a placebo throughout the study. In order to track the effect the drug had on pain, each patient maintained a daily pain journal, rating their pain on a numerical rating score (NRS) of 0 to 10. Using these pain journals a weekly NRS was averaged and mean was determined for both the mirtazapine group and placebo group at specific time points.

The results of the study showed the group of patients who received mirtazapine demonstrated a decrease in mean NRS pain scores from week 2 to week 8. After week 8, the mean NRS pain scores remained constant for this group. These results showed a notably greater reduction in mean NRS pain scores for the mirtazapine group than those of the placebo group.

Safety

Participants may experienceany serious adverse event. Serious adverse events typically include any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an ‘important medical event’ that may jeopardise the person, or may require an intervention to prevent one of the above characteristics or consequences.

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Study Reference : PubMed

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