Best painkiller for fibromyalgia

When Fibromyalgia Painkillers Stop Working

Common pain symptoms of fibromyalgia include stabbing, burning, shooting, or throbbing pain in any area of the body. Pain is usually worse in the morning. People with fibromyalgia may have tender areas on their neck, shoulders, back, or legs that are painful when touched.

And fibromyalgia pain can become even worse with physical or emotional stress. Common stressors that may make your fibromyalgia pain worse include a traumatic event, such as a car accident, repetitive physical traumas, or a physical illness.

Getting this pain under control is not easy. But it is possible.

“Pain medications for fibromyalgia tend to wane and lose their effectiveness over time,” explains Micha Abeles, MD, a rheumatologist at the University of Connecticut Health Center in Farmington. “It is often necessary to wean a patient off one medication and add new medications over time. If pain medication is not working, it is necessary to evaluate the patient to identify any psychosocial events that could be acting as stressors and making their pain worse.”

Switching to a new fibromyalgia pain medication is easier if you taper one medicine gradually before starting a new one. Always follow your doctor’s directions carefully and never stop a medication on your own.

7 Treatment Options for Fibromyalgia

Important options for treating fibromyalgia include finding the right pain medication, getting the proper psychological support, trying complementary therapies, and finding the right treatment team. If your fibromyalgia treatment is not working, ask your doctor to help you explore these options:

  • Pain medications. There are a number of medications now approved for fibromyalgia pain, including pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella). The narcotic-like painkiller tramadol (Ultram) has also been effective for fibromyalgia. “Switching between medications may be necessary and can be made easier with samples or vouchers to decrease the financial cost for the patient,” advises Dr. Abeles.
  • Antidepressant medications. Tricyclic antidepressants and selective serotonin reuptake inhibitor antidepressants are frequently used for fibromyalgia and have been successful in controlling symptoms of pain, sleep disturbances, fatigue, and depression.
  • Sleep management. People with fibromyalgia often have trouble getting enough sleep — and lack of sleep can make fibromyalgia symptoms worse. Make sure you avoid caffeine and stick to a strict sleep schedule. Ask your doctor if a sleep aid medication might help.
  • Social and psychological support. The stress of living with a chronic painful disease like fibromyalgia can make your symptoms worse. Research shows that increasing social support reduces fibromyalgia symptoms, such as pain. You may benefit from a fibromyalgia support group. Professional counseling to help you develop coping skills and better manage your symptoms has also been shown to be helpful.
  • Exercise. Exercise is an important part of feeling better if you have fibromyalgia. Studies show that exercise can help you improve your fitness level, feel better about yourself, and reduce the number of painful pressure points in fibromyalgia.
  • Acupuncture. One survey found that about 20 percent of people diagnosed with fibromyalgia and treated at a university-based clinic tried acupuncture within a two-year period. Some studies have found that acupuncture can help relieve fibromyalgia pain, but other reports say the effects are not long-lasting and the treatment doesn’t help with the fatigue or sleep problems common with fibromyalgia.
  • Other alternative treatments. Although there’s no strong evidence for most alternative treatments for fibromyalgia, many people who have tried these alternative approaches report significant improvement in their symptoms. These treatments include therapeutic message, yoga, biofeedback, hypnosis, chiropractic manipulation, and nutritional supplements. Always let your medical team know about any alternative treatments you’re contemplating.

If you are being treated for fibromyalgia and your pain medications are not as effective as in the past, you have options. Remember that it is common for people with fibromyalgia to try different types of medications and other management strategies. It is also important to make sure you have a sympathetic, knowledgeable team of experts to help you manage your fibromyalgia symptoms.

Fibromyalgia is an unpredictable disease that requires a flexible treatment plan. One of the best things you can do is to educate yourself about fibromyalgia so that you can work closely with your treatment team and be a good advocate for yourself.

Medications to Ease Fibromyalgia Symptoms

Medication plays a role in controlling fibromyalgia symptoms, but there is no single medication that cures or controls the condition. Finding the best options may be a process of trial and error.

3 Medications Approved to Treat Fibromyalgia

The U.S. Food and Drug Administration has approved three medications specifically for adults with fibromyalgia:

  • Pregabalin (known by its brand name, Lyrica) is designed to ease pain and anxiety and help with certain sleep problems. It was originally designed to treat seizures, and limits the body’s release of chemicals that relay pain. Side effects such as weight gain, dry mouth, and dizziness may be experienced.
  • Duloxetine (brand name Cymbalta), an anti-depressant, eases pain and improves functioning. Itching, nausea, and agitation are some of the potential side effects.
  • Milnacipran HCI (brand name Savella) works like an anti-depressant, helping the body reduce feelings of pain and fatigue. Among possible side effects are nausea, constipation, and dizziness.

Side effects of anti-depressants may also include a greater incidence of depression, suicidal thinking or actions, and heart palpitations. The doctor should be contacted about any side effects.

See Treating Depression and Chronic Pain


‘Off-Label’ Medications for Fibromyalgia

Doctors may recommend medications other than (or in addition to) the three FDA-approved drugs approved to treat fibromyalgia. This practice is called “off-label” use, and is common in treating fibromyalgia. Medications that ease pain can encourage individuals to move more throughout the day, which in turn can improve lung capacity and muscle tone. Medications may also be helpful in dealing with sleep problems, depression, and anxiety.

See Medications Used to Help Treat Insomnia

A prescription for anti-depressants does not mean the doctor thinks the patient is depressed; these medications are chosen because they may reduce an individual’s symptoms.

See Doctors Who Treat Fibromyalgia

Off-label medications often prescribed include:

  • Some older antidepressants such as amitriptyline (Elavil), nortriptyline (Pamelor), and doxepin (Sinequan) ease pain and promote quality sleep. This group of medications, however, has potential side effects already common with fibromyalgia, including morning sleepiness, confusion, and urinary retention.
  • Cyclobenzaprine (often known by the brand name, Flexeril) helps with pain and sleep issues, but its antidepressant effects are minimal. It is used only as a short-term muscle relaxant.
  • Gabapentin (brand names Neurontin, Gralise), developed for epilepsy, relieves pain in certain situations.

Research on another medication, low-dose naltrexone, has been encouraging for treating fibromyalgia. Used for years to help people break drug addictions, research suggests low-dose naltrexone may help improve mood and outlook among people with fibromyalgia.1

Acetaminophen used alone or in combination with Tramadol (brand name Ultram), is sometimes useful in treating pain. Tramadol is sometimes described as “narcotic-like,” and is used for fibromyalgia pain when other options have not worked.

Research has not been definitive on two treatments—local injections at tender points and transcutaneous nerve stimulation (TENS)—but these may be helpful in some cases.

See Pill-Swallowing Techniques and Alternatives to Oral Medications

In This Article:

  • What You Need to Know About Fibromyalgia
  • Characteristic Symptoms of Fibromyalgia
  • How to Get a Fibromyalgia Diagnosis
  • Multi-Specialty Fibromyalgia Treatment
  • Medications to Ease Fibromyalgia Symptoms

Medications That Are Not Considered Effective

Some medications used effectively for other conditions do not have the same effect in fibromyalgia treatment:

  • Non-steroidal anti-inflammatory medications are typically not helpful in treating fibromyalgia, except as an ingredient in drug combinations.
  • Narcotic pain medications, also called opioids, are strong pain medications but are generally avoided because they do not usually relieve fibromyalgia pain. In addition, opioids have many serious potential side effects and can be addictive for some people.

See Coping with Constipation Caused by Opioid Medication


Drugs that work in different ways are often combined to treat the multiple problems in fibromyalgia. Some patients also find that a medication loses its effect over time, requiring a new approach.

See Dysphagia and Difficulty Swallowing Medications

US Pharm. 2016;41(3):51-54.

ABSTRACT: Pain is the hallmark of fibromyalgia, which has sparked the theory that fibromyalgia is neurogenic in origin because it is associated with a central amplification of pain perception. Fibromyalgia is more often diagnosed in women, and patients who are younger upon diagnosis have a poorer prognosis and quality of life. The pain of fibromyalgia is hard to control. Possible mechanisms include central and autonomic nervous system dysfunction, as well as genetic and environmental factors. Treatment is difficult and should include both pharmacologic and nonpharmacologic options. There is no gold standard for treatment, and most patients use medications from various classes. The three FDA-approved medications are duloxetine, milnacipran, and pregabalin, with selection based on the patient’s overall characteristics.

Fibromyalgia syndrome, which was first described more than 100 years ago, is defined as chronic, widespread musculoskeletal pain characterized by both somatic and psychological symptoms.1,2 Aches, stiffness, soft-tissue tenderness, fatigue, sleep disturbances, anxiety, and cognitive dysfunction are among the symptoms of fibromyalgia.1,3 Fibromyalgia is commonly seen with other conditions, such as irritable bowel syndrome, low back pain, headaches, arthritis, and posttraumatic stress disorder.3,4 The first official diagnostic guidelines were published in 1990 by the American College of Rheumatology, followed by treatment guidelines published by the American Pain Society in 2005.2

In the United States, an estimated 2% to 8% of adults experience fibromyalgia, and studies indicate a global prevalence of 2.7%.1,4 Fibromyalgia is more common in persons older than 50 years (mostly ages 60-79 years) and in persons with lower socioeconomic status and education. Fibromyalgia is diagnosed three times more often in women than in men, with an incidence of 6.88 new cases of fibromyalgia per 1,000 in males and 11.28 new cases per 1,000 in females.1 Patients who are diagnosed at an earlier age (<39 years) have a poorer prognosis and quality of life. Overall, patients with fibromyalgia have a reduced quality of life and report having difficulties in everyday tasks, including bathing, lifting or carrying, and walking up stairs.2

Pathogenesis of Fibromyalgia

The fact that pain is the hallmark of fibromyalgia has caused experts to believe that the disorder is neurogenic in origin, as it is associated with a central amplification of pain perception characterized most prominently by hyperalgesia (increased response to painful stimuli) and allodynia (pain from stimuli not normally painful). Possible mechanisms include dysfunction of the central and autonomic nervous systems, genetic factors, and environmental factors, including infections and physical trauma. Studies have also linked fibromyalgia to sexual abuse, psychological stress, and deployment to war.2,3 Brain imaging has shown abnormalities in pain processing and reduced gray-matter volume in patients with fibromyalgia. These patients also exhibit polymorphisms to the serotonin receptor 2A region of chromosome 13 and the human leukocyte antigen region of chromosome 6, as well as abnormalities in catechol-O-methyltransferase.3

Diagnosis of Fibromyalgia

The diagnosis of fibromyalgia is subjective and is based on the patient’s complaint of pain and the accompanying symptoms previously mentioned. The pain is usually above or below the waist and bilateral. Patients whose pain lasts more than 3 months and who have 11 out of 18 tender-point sites are diagnosed with fibromyalgia syndrome.3,4 In 2010, the American College of Rheumatology published new diagnostic criteria, which were modified in 2011; currently, diagnosis is based on symptoms evaluated by the Widespread Pain Index and the Symptom Severity Scale. These evaluations have 83% sensitivity and 67% specificity.2

Treatment of Fibromyalgia

Because fibromyalgia is a chronic, complex condition with various comorbidities, treatment is difficult and should include both pharmacologic and nonpharmacologic options. There is no gold standard for treatment, and most patients use various medications from a number of classes to relieve their pain. Evidence-based guidelines recommend the use of at least two nonpharmacologic therapies combined with pharmacologic treatments for the management of fibromyalgia. Cognitive behavioral therapy (CBT), which is often used in patients with depression and anxiety, has been shown to be beneficial in fibromyalgia. Meta-analyses of randomized clinical trials have concluded that CBT reduces the fear and anxiety associated with fibromyalgia.3 Exercise has also been found to improve overall well-being, physical function, reports of pain, tenderness, and muscle strength. Complementary treatment options such as tai chi and acupuncture have also been used; however, efficacy data for acupuncture are lacking.2

As previously stated, fibromyalgia is a complex condition requiring different treatment modalities, and no single therapy is superior to the others with regard to efficacy. The various guidelines have different approaches to treatment; however, there is some homogeneity in the medications used. Currently, three medications are approved for the treatment of fibromyalgia syndrome. Pregabalin, which was the first drug to gain FDA approval for diabetic neuropathy, is an anticonvulsant and analgesic that works by binding to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system.1,3 Numerous meta-analyses and clinical trials have concluded that pregabalin improved pain, fatigue, depressed mood, sleep disturbance, and health-related quality of life. The serotonin-norepinephrine reuptake inhibitors (SNRIs) duloxetine and milnacipran, which are the other two medications FDA-approved for fibromyalgia, are recommended by all clinical guidelines.1

In addition to these FDA-approved medications, a variety of drugs may be used off-label to treat the symptoms of fibromyalgia. The most notable of these is amitriptyline, a tricyclic antidepressant (TCA). Amitriptyline exerts its effect on pain modulation via serotonin and norepinephrine, and for many years it was the mainstay of therapy.5 In a systematic review evaluating the efficacy and acceptability of amitriptyline, duloxetine, and milnacipran, amitriptyline was found to improve pain, fatigue, and sleep and was concluded to be superior to duloxetine and milnacipran in those areas.1

Cyclobenzaprine, which is similar in structure to TCAs, has been shown to improve pain and sleep disturbances; however, many patients have reported adverse effects.2 Tramadol, a synthetic opioid receptor agonist with properties similar to those of SNRIs, inhibits the reuptake of biogenic amines—including serotonin and norepinephrine (similar to SNRI antidepressants)—and acts as a weak agonist at the mu-opioid receptor.4 Although some literature states that it may be used as first-line therapy, tramadol lacks FDA approval and is recommended as an alternative to duloxetine, milnacipran, or pregabalin.4 Nonsteroidal anti-inflammatory drugs have demonstrated benefits in combination with antidepressants or anticonvulsants, but they decrease the antidepressant action of selective serotonin reuptake inhibitors (SSRIs) and therefore are not used often.3

TABLE 1 summarizes the medications and lists common dosing and counseling points for pharmacists.

FDA-Approved Medications

Pregabalin has effects on the release of glutamate, norepinephrine, and substance P that may contribute to the reduction of pain in patients with fibromyalgia.2 Pregabalin should be initiated at a dosage of 75 mg twice daily and titrated up to a target of 225 mg twice daily, depending on the patient’s creatinine clearance. Total daily doses of 300 mg, 450 mg, or 600 mg can reduce pain by more than 30% if the patient can tolerate the side effects of dizziness, somnolence, dry mouth, weight gain, and peripheral edema, especially at 600 mg.1,2

Duloxetine and milnacipran are SNRIs, but their exact mechanisms are not known.2 Initiating duloxetine at 30 mg once daily and titrating up after 1 week to 60 mg daily can help reduce the patient’s fibromyalgia pain, as well as anxiety and depression. The starting dosage of milnacipran is 12.5 mg daily, and the agent may be slowly titrated up to 50 mg twice daily. This regimen relieves the patient’s fibromyalgia pain, anxiety, and depression, but adjustments are needed in patients with renal insufficiency and those unable to tolerate the side effects.1,2

Treatment regimens for fibromyalgia have never been clinically compared. Since there are no direct clinical comparisons of the FDA-approved drugs, a systematic review was conducted to determine the similarities, advantages, and side effects of these medications.2 Compared with placebo, duloxetine, milnacipran, and pregabalin were superior in the treatment of fibromyalgia.1,2 Duloxetine was similar to placebo in the treatment of fatigue in fibromyalgia patients.2 Adverse effects between all of the FDA-approved medications were similar, except that headache and nausea were more common in duloxetine and milnacipran patients than in those receiving pregabalin.1,2

Off-Label Medications

Off-label therapies, including amitriptyline, fluoxetine, gabapentin, cyclobenzaprine, and tramadol, have been shown to reduce patients’ fibromyalgia pain.1,2,5 In evaluations of two different dosages of amitriptyline, 25 mg improved patients’ pain, sleep disturbance, and fatigue, but the effectiveness of the 50-mg dosage was comparable to that of placebo, probably owing to high rates of adverse reactions.1,2 Adverse reactions in patients taking amitriptyline included dry mouth, somnolence, gastrointestinal disturbances, and weight gain.1,2 Cyclobenzaprine, which is similar in structure to TCAs, has been found helpful in fibromyalgia patients; 10 to 30 mg daily produced improvements in sleep and pain, but not in fatigue or tender-point pain.1,2 Gabapentin is similar to pregabalin, but limited studies have been done on its benefits for fibromyalgia.1,2 Dosages of 1,200 to 2,400 mg daily have resulted in a reduction in pain severity.1,2 Fluoxetine (SSRI) dosages of 10 mg to 80 mg daily have produced reductions in pain, depression, fatigue, and overall symptoms.1,2 A lower dosage was less effective, but its use in combination with other medications, such as amitriptyline, or with complementary/alternative methods, such as acupuncture, has provided relief.1 Finally, tramadol is a weak mu-opioid receptor agonist and weak serotonin and norepinephrine antagonist that has resulted in relief of fibromyalgia pain.1 Tramadol can be paired with acetaminophen to reduce pain even further.1

TCAs were the mainstay of therapy for fibromyalgia for many years. Amitriptyline, in particular, has been extensively studied for fibromyalgia treatment.1,2 Although the clinical trials of amitriptyline are old and involved small numbers of patients, a systematic review revealed that amitriptyline tended to show superiority over duloxetine, pregabalin, and milnacipran.2 Another meta-analysis found that amitriptyline was similar to the FDA-approved medications for the treatment of fibromyalgia.2 Given the flaws in previous studies, amitriptyline cannot be recommended as the gold standard for treatment of fibromyalgia until further studies are conducted.2


Fibromyalgia is a difficult disorder to treat. Based on studies and recommendations, it would be advisable to first treat patients based on their most significant complaint. When an FDA-approved medication for fibromyalgia is being selected, treatment should be tailored to the individual patient.

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You may need to take several different types of medicines for fibromyalgia, including painkillers and antidepressants.


Simple painkillers that are available over the counter from a pharmacy, such as paracetamol, can sometimes help relieve the pain associated with fibromyalgia.

But these are not suitable for everyone, so make sure you read the manufacturer’s instructions that come with the medication before using them.

If over-the-counter painkillers are not effective, your GP (or another healthcare professional treating you) may prescribe a stronger painkiller, such as codeine or tramadol.

But these painkillers can be addictive and their effect tends to weaken over time.

This means that your dose may need to be gradually increased and you could experience withdrawal symptoms if you stop taking them.

Other side effects include diarrhoea and extreme tiredness (fatigue).


Antidepressant medication can also help relieve pain for some people with fibromyalgia.

They boost the levels of certain chemicals that carry messages to and from the brain, known as neurotransmitters.

Low levels of neurotransmitters may be a factor in fibromyalgia, and it’s believed that increasing their levels may ease the widespread pain associated with the condition.

There are different types of antidepressants. The choice of medicine largely depends on the severity of your symptoms and any side effects the medicine may cause.

Antidepressants used to treat fibromyalgia include:

  • tricyclic antidepressants, such as amitriptyline
  • serotonin-noradrenaline reuptake inhibitors (SNRIs), such as duloxetine and venlafaxine
  • selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and paroxetine

A medication called pramipexole, which is not an antidepressant but also affects the levels of neurotransmitters, is sometimes used as well.

Antidepressants can cause a number of side effects, including:

  • feeling sick
  • a dry mouth
  • drowsiness
  • feeling agitated, shaky or anxious
  • dizziness
  • weight gain
  • constipation

For information on the side effects of your particular medication, check the patient information leaflet that comes with it.

Medication to help you sleep

As fibromyalgia can affect your sleeping patterns, you may want medicine to help you sleep.

If you’re sleeping better, you may find that other symptoms are not as severe.

Speak to your GP if you think you could benefit from a medicine like this.

They may recommend an over-the-counter remedy, or prescribe a short course of a stronger medication.

Some antidepressants may also improve your sleep quality.

Read more about treating insomnia for information on good sleeping techniques and medicines to help you sleep.

Muscle relaxants

If you have muscle stiffness or spasms (when the muscles contract painfully) as a result of fibromyalgia, your GP may prescribe a short course of a muscle relaxant, such as diazepam.

These medicines may also help you sleep better because they can have a sedative (sleep-inducing) effect.


You may also be prescribed an anticonvulsant (anti-seizure) medicine, as these can be effective for those with fibromyalgia.

The most commonly used anticonvulsants for fibromyalgia are pregabalin and gabapentin.

These are normally used to treat epilepsy, but research has shown they can improve the pain associated with fibromyalgia in some people.

Some common side effects of pregablin and gabapentin include:

  • dizziness
  • drowsiness
  • swelling of your hands and feet (oedema)
  • weight gain


Antipsychotic medicines, also called neuroleptics, are sometimes used to help relieve long-term pain.

Studies have shown that these medications may help conditions like fibromyalgia, but further research is needed to confirm this.

Possible side effects include:

  • drowsiness
  • tremors (shaking)
  • restlessness

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