Which medications in the drug class Antidepressants are used in the treatment of Fibromyalgia?

Updated: Apr 23, 2020
  • Author: Chad S Boomershine, MD, PhD, CPI, CPT; Chief Editor: Herbert S Diamond, MD  more...
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Low-dose TCAs have proven to have short-term efficacy for pain control, improved sleep, and improved sense of well-being in patients with fibromyalgia. However, adverse effects (eg, dry mouth, drowsiness, weight gain) limit patient acceptance.

Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), fluvoxamine, paroxetine (Paxil, Pexeva), and sertraline (Zoloft), improve symptoms in fibromyalgia but have largely been replaced as a treatment for pain by dual serotonin/norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor), desvenlafaxine (Pristiq), milnacipram (Savella), [136] or duloxetine (Cymbalta). [137, 138, 139]

Milnacipram has been approved for use in fibromyalgia by the FDA. Duloxetine has been shown to improve pain in fibromyalgia irrespective of comorbid depression [140] and is currently approved by the FDA for pain in fibromyalgia.

A useful combination is a TCA (eg, amitriptyline or cyclobenzaprine in low dosage at bedtime) and an SNRI. Patients taking either SSRIs or SNRIs should be carefully monitored for worsening depression or emergence of suicidal thoughts.


Amitriptyline inhibits the reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases their concentration in the CNS.

Duloxetine (Cymbalta)

Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake. Its antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in CNS. It is indicated for fibromyalgia in adults and adolescents aged 13-17 y.

Milnacipran (Savella)

Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI). Its exact mechanism of central pain inhibitory action and ability to improve symptoms of fibromyalgia remain unknown. It is indicated for fibromyalgia.

Venlafaxine (Effexor, Effexor XR)

Vanlafaxine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake.

Desvenlafaxine (Pristiq)

Desvenlafaxine inhibits neuronal serotonin and norepinephrine reuptake.

Levomilnacipran (Fetzima)

A potent inhibitor of neuronal serotonin and norepinephrine reuptake, levomilnacipran inhibits norepinephrine uptake with ~3-fold higher potency in vitro than serotonin, without directly affecting the uptake of dopamine or other neurotransmitters

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