As of 2018, the only tricyclic antidepressant (TCA) that has sufficient evidence is amitriptyline.For most people with fibromyalgia, the potential benefits of treatment with the serotonin and noradrenaline reuptake inhibitors (SNRI) duloxetine and milnacipran and the TCAs, such as amitriptyline, are outweighed by significant adverse effects (more adverse effects than benefits), however, a small number of people may experience relief from symptoms with these medications. In addition, while amitriptyline has been used as a first line treatment, the quality of evidence to support this use and comparison between different medications is poor. Very weak evidence indicates that a very small number of people may benefit from treatment with the tetracyclic antidepressant mirtazapine, however, for most, the potential benefits are not great and the risk of adverse effects and potential harm outweighs any potential for benefit.The length of time that antidepressant medications take to be effective at reducing symptoms can vary. Any potential benefits from the antidepressant amitriptyline may take up to three months to take effect and it may take between three and six months for duloxetine, milnacipran, and pregabalin to be effective at improving symptoms. Some medications have the potential to cause withdrawal symptoms when stopping so gradual discontinuation may be warranted particularly for antidepressants and pregabalin.There is tentative evidence that the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) appear to be similar. SSRIs may be used to treat depression in people diagnosed with fibromyalgia.Tentative evidence suggests that monoamine oxidase inhibitors (MAOIs) such as pirlindole and moclobemide are moderately effective for reducing pain.
Transcutaneous electrical nerve stimulation (TENS)
Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents to the skin to stimulate peripheral nerves. TENS is widely used to treat pain and is considered to be a low-cost, safe, and self-administered treatment. As such, it is commonly recommended by clinicians to people suffering from pain. On 2019, an overview of eight Cochrane reviews was conducted, covering 51 TENS-related randomized controlled trials. The review concluded that the quality of the available evidence was insufficient to make any recommendations. A later review concluded that transcutaneous electrical nerve stimulation may diminish pain in the short-term, but there was uncertainty about the relevance of the results.Preliminary findings suggest that electrically stimulating the vagus nerve through an implanted device can potentially reduce fibromyalgia symptoms. However, there may be adverse reactions to the procedure. Noninvasive brain stimulation
Noninvasive brain stimulation includes methods such as transcranial direct current stimulation and high-frequency repetitive transcranial magnetic stimulation (TMS). Both methods have been found to improve pain scores in neuropathic pain and fibromyalgia.A 2021 meta-analysis of multiple intervention types concluded that magnetic field therapy and transcranial magnetic stimulation may diminish pain in the short-term, but conveyed an uncertainty about the relevance of the result. Several 2022 meta-analyses focusing on transcranial magnetic stimulation found positive effects on fibromyalgia. Repetitive transcranial magnetic stimulation improved pain in the short-term and quality of life after 5–12 weeks. Repetitive transcranial magnetic stimulation did not improve anxiety, depression, and fatigue. Transcranial magnetic stimulation to the left dorsolateral prefrontal cortex was also ineffective.