Key takeaways

Cymbalta and Lyrica are both approved treatments for diabetic peripheral neuropathy and fibromyalgia. Cymbalta is an SNRI antidepressant, and affects serotonin and norepinephrine. Lyrica is an analgesic and anticonvulsant, and slows nerve signal transmission.
Common side effects of Cymbalta include headache, nausea, dry mouth, and sleepiness. Common side effects of Lyrica include dizziness, drowsiness, weight gain, and fluid retention.
Both medications are considered safe and effective for treating pain related to diabetic neuropathy, either as monotherapy or in combination, according to clinical trials and observational studies.
Cymbalta is generally covered by insurance and Medicare, costing around $10 with a coupon for a one-month supply, while Lyrica, also covered, can cost up to $287 without insurance but less than $15 with a coupon.

Cymbalta and Lyrica treat a variety of health conditions, but they are both approved treatments for diabetic peripheral neuropathy and fibromyalgia. Cymbalta is a serotonin norepinephrine reuptake inhibitor (SNRI) while Lyrica is an analgesic and anticonvulsant. They work differently but both can be used to treat muscle and nerve pain. Use this guide to compare Cymbalta and Lyrica and learn more about how they work, the conditions they treat, and their possible side effects.

What are the main differences between Cymbalta and Lyrica?

Cymbalta (duloxetine) is a prescription drug used to treat a variety of disorders including diabetic neuropathy and fibromyalgia. It is perhaps more commonly known for its indication to treat major depression and generalized anxiety disorder. It is classified as a serotonin norepinephrine reuptake inhibitor (SNRI) and works by increasing available serotonin and norepinephrine, two neurotransmitters known for their role in mood and disposition. Its role in pain relief is also thought to be through its action on serotonin and norepinephrine.

Other SNRIs such as Pristiq (desvenlafaxine), Effexor (venlafaxine), and Savella (milnacipran) are not approved for indications related to neuropathic pain. Cymbalta is available in oral capsules in strengths of 20 mg, 30 mg, 40 mg, and 60 mg.

Lyrica (pregabalin) is a prescription drug also approved in the treatment of diabetic neuropathy and fibromyalgia. Lyrica also carries other indications for disorders such as seizures and other types of neuropathic pain. Lyrica is classified as both an analgesic, or pain reliever, and an anticonvulsant. Lyrica works by slowing signal transmission in the nerve pathways. It is chemically similar to another drug, Neurontin (gabapentin).

Lyrica is considered a controlled substance by the Drug Enforcement Agency (DEA) due to its potential for dependency and abuse. Lyrica is subject to federal and state prescribing laws for controlled substances.

Lyrica is available as an oral capsule in a variety of strengths including 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg. It is also available as a 20 mg/ml oral solution as well as extended-release capsules in 82.5 mg, 165 mg, and 330 mg.

Main differences between Cymbalta and Lyrica
	Cymbalta	Lyrica
Drug class	SNRI	Analgesic/anticonvulsant
Brand/generic status	Brand and generic available	Brand and generic available
What is the generic name?	Duloxetine	Pregabalin
What form(s) does the drug come in?	Capsule	Immediate and extended-release capsules, oral solution
What is the standard dosage?	60 mg once daily	50- 100 mg three times daily
How long is the typical treatment?	Long term	Long term
Who typically uses the medication?	Adolescents and adults	Children and adolescents (seizures only), adults

Conditions treated by Cymbalta and Lyrica

Cymbalta has common uses across a broad range of indications. It is used in the treatment of major depressive disorder and generalized anxiety disorder. It is also indicated in the treatment of fibromyalgia, pain associated with diabetic neuropathy, and chronic pain associated with musculoskeletal disorders such as osteoarthritis and chronic back pain. Cymbalta is sometimes used off-label to treat stress urinary incontinence (SUI). Off-label use refers to use for an indication in which it has not been approved by the Food and Drug Administration (FDA).

Lyrica is used as an analgesic in neuropathic pain-related disorders such as diabetic neuropathy, postherpetic neuralgia, fibromyalgia, and spinal cord injuries. Lyrica is also approved as an adjunct treatment for partial seizures. Lyrica has a few off-label uses as well, including social anxiety disorder and generalized anxiety disorder.

Condition	Cymbalta	Lyrica
Diabetic peripheral neuropathic pain	Yes	Yes
Pain associated with postherpetic neuralgia	No	Yes
Pain associated with spinal cord injury	No	Yes
Chronic musculoskeletal pain	Yes	No
Fibromyalgia	Yes	Yes
Adjunct treatment of partial seizures	No	Yes
Major depressive disorder	Yes	No
Generalized anxiety disorder	Yes	Off-label
Social anxiety disorder	No	Off-label
Stress urinary incontinence	Off-label	No

Is Cymbalta or Lyrica more effective?

A randomized clinical trial known as the “Combo-DN Study” compared the effects of high dose Cymbalta and Lyrica alone, and their combination in patients for whom monotherapy was not effective in the treatment of pain related to diabetic neuropathy. This study found that the improvement in pain was similar in patients on Cymbalta along, Lyrica alone, and the combination of the two. While it failed to show that any one treatment group was superior, it did provide evidence that all three treatment options were safe and effective in pain related to diabetic neuropathy.

A separate observational study concluded that Cymbalta may be more effective at treating neuropathic pain related to diabetic neuropathy, though Lyrica may have better tolerability for patients in terms of its side effect profile.

This is not intended to be medical advice. Only your physician and healthcare team can determine which treatment is best for you and your condition.

Coverage and cost comparison of Cymbalta vs. Lyrica

Cymbalta is a prescription medication whose generic is typically covered by commercial and Medicare insurance plans. Without insurance, a one-month supply could cost you $470. With a coupon for generic Cymbalta (Duloxetine Hcl), your cost is around $10.

Lyrica is a prescription medication that is covered by both commercial and Medicare insurance plans in its generic form. A one-month supply of Lyrica may cost you as much as $287 without insurance. A coupon for the generic form could reduce your cost to less than $15.

	Cymbalta	Lyrica
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare Part D?	Yes	Yes
Quantity	30, 60 mg capsules	30, 75 mg capsules
Typical Medicare copay	Varies depending on plan	Varies depending on plan
SingleCare cost	$8+	$14+

Common side effects of Cymbalta vs. Lyrica

The side effect profiles for Cymbalta and Lyrica vary from each other significantly in some aspects. For example, the manufacturer for Cymbalta reported that a significant number of patients experienced headache during clinical trials, while this adverse event was not reported for Lyrica at all. Sweating and diarrhea were also reported with Cymbalta but not with Lyrica.

Lyrica is associated with a significant amount of dizziness and drowsiness, and this can make it difficult to drive and do daily functions. Lyrica is also linked to blurry vision, weight gain, and fluid retention which may also affect the quality of life.

This is not intended to be an all-inclusive list of adverse effects. If you experience these or other side effects and they are bothersome or intolerable, you should consult your prescriber.

	Cymbalta		Lyrica
Side effect	Applicable?	Frequency	Applicable?	Frequency
Nausea	Yes	23%	No	n/a
Dry mouth	Yes	13%	Yes	5%
Sweating	Yes	6%	No	n/a
Diarrhea	Yes	9%	No	n/a
Constipation	Yes	9%	Yes	4%
Flatulence	No	n/a	Yes	2%
Dizziness	Yes	9%	Yes	21%
Somnolence	Yes	10%	Yes	12%
Headache	Yes	14%	No	n/a
Increased blood pressure	Yes	2%	No	n/a
Decreased appetite	Yes	7%	No	n/a
Peripheral edema	No	n/a	Yes	9%
Weight gain	No	n/a	Yes	4%
Edema	No	n/a	Yes	2%
Ataxia	No	n/a	Yes	3%
Vertigo	No	n/a	Yes	3%
Confusion	No	n/a	Yes	2%
Blurry vision	No	n/a	Yes	4%

Source: Cymbalta (DailyMed) Lyrica (DailyMed)

Drug interactions of Cymbalta vs. Lyrica

Cymbalta should be used cautiously with other serotonergic drugs. Increased serotonin has been linked to serotonin syndrome. Serotonin syndrome is characterized by symptoms such as headache, confusion, sweating, nausea, and diarrhea. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine or paroxetine, the herbal supplement St. John’s Wort, and the triptan class of migraine agents such as eletriptan or almotriptan. Lyrica has no interactions with serotonergic drugs.

Both Cymbalta and Lyrica should be used cautiously with tricyclic antidepressants such as amitriptyline and nortriptyline. They should also be used cautiously or avoided with monoamine oxidase inhibitors (MAOIs) such as selegiline.

This is not intended to be a comprehensive list of drug interactions. You should consult your pharmacist or doctor for a complete list.

Drug	Drug Class	Cymbalta	Lyrica
Almotriptan Eletriptan Oxitriptan	5HT Agonist/Triptans (antimigraine agents)	Yes	No
Amphetamine salts Dexmethylphenidate Methylphenidate	Amphetamines	Yes	Yes
Aripiprazole	Antipsychotic	Yes	Yes
Aspirin Ibuprofen Naproxen Diclofenac	Nonsteroidal anti-inflammatory drugs (NSAIDs)	Yes	No
Buspirone	Antianxiety	Yes	Yes
Fluoxetine Citalopram Paroxetine Escitalopram	SSRIs	Yes	No
Hydroxychloroquine	Aminoquinolone/Antimalarial	No	Yes
Linezolid	Antibiotic	Yes	No
Metaxalone	Muscle relaxers	Yes	Yes
Pimozide	Antipsychotic	No	Yes
Selegiline Phenelzine Rasagiline	Monoamine oxidase inhibitor (MAOI)	Yes	Yes
St. John’s Wort	Herbal supplement	Yes	No
Tramadol	Opiate pain reliever	Yes	Yes
Amitriptyline Clomipramine Doxepin Nortriptyline	Tricyclic antidepressants	Yes	Yes

Warnings of Cymbalta and Lyrica

Cymbalta will not produce an immediate remission of pain, depression disorder, or anxiety disorder. It will take a minimum of two weeks to notice any change in most patients, and up to four to six weeks to realize the full effect of the medication. Do not prematurely discontinue your medication with the belief that it is not working without first speaking to your prescriber.

Patients with depression may experience a worsening of depression or suicidal thoughts whether or not they are taking antidepressant medications. These conditions may worsen until remission is achieved. Cymbalta may increase suicidal ideation and thoughts among teens and young adults, especially in the early stages of treatment. These patients must be monitored closely if this treatment is deemed medically necessary. A therapy change may be necessary if symptoms suddenly arise or get worse.

Antiepileptic drugs, like Lyrica, have also been linked to suicidal ideation. Patients who start Lyrica should be monitored for an emergence or worsening of depression.

There have been reports of liver failure, sometimes fatal, with Cymbalta. These cases may present with abdominal pain and elevated liver enzymes with or without jaundice. The consumption of alcohol may increase this risk, and therefore this combination should be avoided.

Lyrica is a controlled substance due to its potential for misuse and abuse. Caution should be used before starting Lyrics therapy in a patient with a personal or family history of substance abuse.

Frequently asked questions about Cymbalta vs. Lyrica

What is Cymbalta?

Cymbalta is a prescription antidepressant medication used in the treatment of major depression, generalized anxiety disorder, and various neuropathic and musculoskeletal pain disorders. Cymbalta is in a class of drugs known as selective serotonin-norepinephrine reuptake inhibitors (SNRIs). Cymbalta is available as an oral capsule in 20 mg, 30 mg, and 60 mg strengths.

What is Lyrica?

Lyrica is a prescription medication that is classified as an analgesic and anticonvulsant. It is used to treat seizures as well as pain related to neuropathic disorders and fibromyalgia. Lyrica is available in a variety of strengths in both immediate and extended-release capsules, as well as an oral solution.

Are Cymbalta and Lyrica the same?

While Cymbalta and Lyrica are useful in similar types of pain-related disorders, they are not the same. Cymbalta is an antidepressant whose actions are mediated through its actions on serotonin and norepinephrine. Lyrica is an analgesic and anticonvulsant whose actions slow nerve signal transmission.

Is Cymbalta or Lyrica better?

Cymbalta and Lyrica have both been shown to be safe and effective both as monotherapy and combination therapy. Which treatment option is right for you will depend on your condition, your medical history, and what your physician thinks is best for you.

Can I use Cymbalta or Lyrica while pregnant?

The FDA considers Cymbalta pregnancy category C, meaning there have not been adequate human studies to determine safety. With Cymbalta, non-teratogenic effects have been observed in newborns following the administration of Cymbalta while pregnant. These include respiratory distress, feeding difficulty, and tremors. In general, either drug should only be used with the benefit to the mother clearly outweighs the risk to the fetus.

Can I use Cymbalta or Lyrica with alcohol?

Patients should avoid significant alcohol intake if taking Cymbalta or Lyrica. Alcohol can increase the toxic effects of both medications and can cause significant psychomotor impairment. With Cymbalta specifically, alcohol increases the incidence of liver impairment.