Are both Cymbalta and Lyrica FDA-approved for fibromyalgia?

Yes. Both Cymbalta (duloxetine) and Lyrica (pregabalin) are FDA-approved for the treatment of fibromyalgia. Lyrica was the first drug ever FDA-approved specifically for fibromyalgia.

Cymbalta vs Lyrica

Q: What is the main difference between Cymbalta and Lyrica?

Cymbalta (duloxetine) is an SNRI antidepressant that works by inhibiting the reuptake of serotonin and norepinephrine. Lyrica (pregabalin) is a gabapentinoid that works by binding to voltage-gated calcium channels in the nervous system. They have completely different mechanisms of action despite overlapping uses in fibromyalgia and diabetic neuropathy.

Q: Is Lyrica a controlled substance?

Yes. Lyrica (pregabalin) is a Schedule V controlled substance in the United States due to its potential for abuse and dependence. Cymbalta (duloxetine) is not a controlled substance.

Q: Which causes more weight gain, Cymbalta or Lyrica?

Lyrica (pregabalin) is associated with significant weight gain and peripheral edema. Cymbalta (duloxetine) tends to be weight-neutral or cause only slight weight gain, making it the option with less weight impact for most patients.

Q: What strengths does Cymbalta come in?

Cymbalta (duloxetine) is available as delayed-release capsules in 20 mg, 30 mg, and 60 mg strengths.

Q: What strengths does Lyrica come in?

Lyrica (pregabalin) is available as capsules in 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg strengths, as well as an oral solution at 20 mg/mL.

Cymbalta

duloxetine HCl

SNRI Antidepressant

Maker: Eli Lilly & Co.
Schedule: Not controlled
Form: Delayed-release capsule

Lyrica

pregabalin

Gabapentinoid

Maker: Pfizer
Schedule: Schedule V (controlled)
Form: Capsule / Oral solution

Mechanism of Action

Cymbalta

Inhibits the reuptake of both serotonin and norepinephrine in the brain and spinal cord. Elevated norepinephrine is thought to modulate descending pain inhibition pathways, explaining its efficacy in neuropathic and musculoskeletal pain.

Lyrica

Binds to the α2δ subunit of voltage-gated calcium channels in the central nervous system, reducing the release of excitatory neurotransmitters like glutamate and substance P. Structurally related to GABA but does not directly act on GABA receptors.

FDA-Approved Indications

Cymbalta

Major depressive disorder (MDD)
Generalized anxiety disorder (GAD)
Fibromyalgia
Diabetic peripheral neuropathy
Chronic musculoskeletal pain

Lyrica

Fibromyalgia
Diabetic peripheral neuropathy
Postherpetic neuralgia
Partial-onset seizures (adjunct)
Spinal cord injury neuropathic pain

Both drugs share FDA approval for fibromyalgia and diabetic peripheral neuropathy — a rare overlap across entirely different drug classes. Lyrica was the first FDA-approved treatment for fibromyalgia (2007). Cymbalta followed (2008).

Available Strengths

Cymbalta — Delayed-Release Capsules

20 mg 30 mg 60 mg

Generic duloxetine is widely available in these same strengths. Capsule beads can be sprinkled on applesive — capsules should not be crushed or chewed.

Lyrica — Capsules & Oral Solution

25 mg 50 mg 75 mg 100 mg 150 mg 200 mg 225 mg 300 mg

Oral solution: 20 mg/mL. Generic pregabalin is available in all capsule strengths. Lyrica CR (extended-release) available in 82.5 mg and 165 mg.

Key Differences at a Glance

Feature	Cymbalta (duloxetine)	Lyrica (pregabalin)
Drug class	SNRI antidepressant	Gabapentinoid / anticonvulsant
Controlled	Not controlled	Schedule V
Abuse potential	Not recognized	Recognized; euphoric effects at higher amounts
Weight effect	Weight-neutral to slight gain	Significant weight gain common
Edema	Uncommon	Peripheral edema common
Sedation	Mild to moderate	More pronounced; somnolence frequent
Discontinuation	Notable discontinuation syndrome (taper required)	Physical dependence; gradual taper required
Antidepressant use	Yes — FDA-approved for MDD	No antidepressant indication (US)
Anxiety (US)	FDA-approved for GAD	Not FDA-approved for GAD in the US*
Seizure use	None	Adjunct for partial-onset seizures
Renal dosing	Not renally dosed; avoid if CrCl <30	Renal dose adjustment required

*Lyrica is approved for GAD in the EU and several other regions, but not in the United States.

Notable Considerations

Cymbalta

Carries a black box warning for suicidality in young adults (≤24) and pediatric patients
Discontinuation syndrome can be significant — avoid abrupt stopping
Approved for stress urinary incontinence in some European countries (as Yentreve)
Treats both pain and the psychological burden of chronic conditions simultaneously

Lyrica

Schedule V: prescriptions may have refill restrictions depending on state law
Weight gain and edema can be treatment-limiting for some patients
Cognitive blunting ("Lyrica brain fog") reported
Effective onset for nerve pain is often faster than with SNRIs

For informational use only. This page does not constitute medical advice and is not a substitute for guidance from a licensed healthcare provider. Drug selection, dosing, and management should always involve a qualified clinician. Information presented reflects FDA labeling; off-label uses exist and may differ. PillID / QuickPillID.com makes no warranty regarding accuracy or completeness.

Frequently Asked Questions

What is the main difference between Cymbalta and Lyrica?

Cymbalta (duloxetine) is an SNRI antidepressant that works by blocking the reuptake of serotonin and norepinephrine. Lyrica (pregabalin) is a gabapentinoid that binds to calcium channels in nerve cells. The mechanisms are completely different — these are not interchangeable drugs — though they overlap in treating fibromyalgia and diabetic neuropathy.

Is Lyrica a controlled substance?

Yes. Lyrica (pregabalin) is classified as a Schedule V controlled substance in the United States. This reflects its potential for misuse and physical dependence. Cymbalta (duloxetine) is not a controlled substance. In practice, this means Lyrica prescriptions may face refill restrictions, prior-authorization requirements, and additional prescriber documentation in certain states.

Which causes more weight gain, Cymbalta or Lyrica?

Lyrica (pregabalin) is associated with significantly more weight gain, often in conjunction with peripheral edema (fluid retention). Weight gain of 7% or more of body weight is not uncommon. Cymbalta (duloxetine) tends to be weight-neutral or cause only slight weight gain over the long term, making it a more favorable option for patients concerned about weight.

What strengths does Cymbalta come in?

Cymbalta (duloxetine) is available as delayed-release capsules in 20 mg, 30 mg, and 60 mg strengths. Generic duloxetine is available in these same strengths from multiple manufacturers.

What strengths does Lyrica come in?

Lyrica (pregabalin) capsules come in 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg. An oral solution at 20 mg/mL is also available. Lyrica CR (extended-release tablets) are available in 82.5 mg and 165 mg.

Are both drugs approved for fibromyalgia?

Yes — both Cymbalta and Lyrica carry FDA approval for fibromyalgia. Lyrica was the first drug ever to receive this specific FDA indication (2007), followed by Cymbalta in 2008. Despite that overlap, they work through entirely different mechanisms: pregabalin modulates calcium channels while duloxetine inhibits monoamine reuptake.

Can Cymbalta treat depression? Can Lyrica?

Cymbalta (duloxetine) is FDA-approved for major depressive disorder and is a first-line antidepressant. Lyrica (pregabalin) has no antidepressant indication in the United States, though it is approved for generalized anxiety disorder in the European Union and other regions.