Are Effexor And Lyrica Comparable For Nerve Pain Treatment?

In our latest question and answer, the pharmacist compares the use of Lyrica and Effexor for the treatment of neuropathic pain (i.e. nerve-type pain).

Are Effexor And Lyrica Comparable For Nerve Pain Treatment?
Jan 23, 2019

Fibromyalgia victim asked

My insurance wants me to take Effexor XR (venlafaxine extended-release) instead of Lyrica. I reacted badly to gabapentin in the past. Are Effexor and Lyrica comparable for nerve pain treatment?

At a glance

  • Lyrica is FDA-approved to treat several forms of neuralgia. Effexor is not FDA-approved in this regard but is commonly used 'off-label'.
  • Both Lyrica and Effexor are effective for treating neuralgia, but most studies indicate that Lyrica may provide slightly better pain relief. However, Effexor may be preferred if also using to treat depression.
  • The side effect profiles of Effexor and Lyrica differ and are a important consideration in regard to drug choice.
  • There are many factors that go into whether or not your insurance covers a certain drug. They may also implement certain requirements before a drug is paid for, such as a 'prior authorization', or 'step-therapy'.


Man Holding Two Different Pills

Effexor (venlafaxine) and Lyrica (pregabalin) are both drugs that are commonly used to treat neuralgia (nerve-type pain).

However, they are significantly different in many aspects, including how they work, how effective they are and their side effect profile. These are all discussed further on.


The most significant difference between Lyrica and Effexor is that they are in different classes of medication and work differently.

Effexor is classified as a serotonin-norepinephrine reuptake inhibitor (SNRI). These drugs are sometimes referred to as 'dual inhibitors.' These drugs work by inhibiting the reuptake of two different neurotransmitters, serotonin, and norepinephrine. SNRI drugs are most commonly prescribed for the treatment of depression but are also used for other indications (such as neuralgia).

Lyrica, on the other hand, does not affect serotonin or norepinephrine. The exact mechanism of action isn't completely understood. Studies show that Lyrica most likely works by:

  • Increasing neuronal levels of GABA, an inhibitory neurotransmitter.
  • Increasing glutamic acid decarboxylase activity. Glutamic acid is an excitatory neurotransmitter and high levels may increase the incidence of neuropathic pain and seizures. Increasing glutamic acid decarboxylase activity would decrease levels of glutamic acid.
  • Decreasing neuronal calcium flow, reducing signal transmission (this is thought to be the primary mechanism by which Lyrica works).

Without going into too much additional detail about how these drugs work, the main point is that they do not work the same way.

Lyrica Or Effexor: Which Is More Effective?

Most studies show that Lyrica and Effexor not only help to reduce painful neuropathy, but they also can improve certain quality of life measures, including:

  • Working ability
  • Sleep interference
  • Mood
  • Social functioning

The vast majority of medical guidelines list Lyrica and Effexor as 'first-line' treatment options. Large review studies (which compile data from various clinical trials and other sources) also list Lyrica and Effexor as good 'first-line' options.

There, unfortunately, haven't been many studies that directly compared Lyrica to Effexor, but the ones that have seem to give a slight edge to Lyrica in regard to pain reduction.

One such study, published in the journal 'Neurology', compared three drugs for the treatment of diabetic neuropathy and concluded the following:

This study showed the efficacy of venlafaxine [Effexor], pregabalin [Lyrica] , and carbamazepine in pain reduction in patients with diabetic neuropathy, although pregabalin was shown to be superior to carbamazepine, and venlafaxine in relieving pain, no significant superiority was shown between carbamazepine, and venlafaxine.

It is certainly possible that we just don't have enough data to make a firm conclusion on which drug is 'better' and the response to any particular one is likely going to vary by individual.

There are many other factors to consider when selecting a drug, aside from their potential effectiveness. For example, Effexor may be a better choice if you are also treating depression.

The side effect profile of each also must be taken into consideration (this topic is discussed in the next section).

It is important to note that Lyrica and SNRI drugs like Effexor can be used together and it is a fairly common practice to do so if necessary. As discussed above, they have different mechanisms by which they work and the combination seems to be more effective than either alone.

Side Effects

The side effect profiles of Lyrica and Effexor are important to consider.

For Lyrica, notable side effects include:

  • Sedation
  • Dizziness
  • Weight gain
  • Fluid retention
  • Blurred vision
  • Constipation
  • Headache
  • Loss of coordination (uncommon)

Lyrica is classified as a controlled substance and therefore has some risk of abuse and dependence.

For Effexor, notable side effects include:

  • Nausea
  • Weight loss
  • Constipation
  • Increased blood pressure
  • Insomnia
  • Dizziness
  • Arrhythmia (uncommon)
  • Increased sweating
  • Headache
  • Sexual dysfunction

Both drugs are recommended to be initiated at low starting doses and increased slowly, to effect, to reduce the severity of potential adverse reactions.

The side effect profile of each is a significant determining factor in which drug to try first for treatment. For one example, if you have high blood pressure or known heart conditions, Lyrica may be a better option since Effexor can raise blood pressure (likely due to its effects on norepinephrine).

Insurance Coverage

Drug coverage is entirely dependent on your specific insurance plan and your drug formulary.

While Effexor XR is available generically, Lyrica is currently only available as a brand name product and is therefore significantly more expensive for your insurance company to pay for.

For many insurance plans, when multiple therapy options exist at significantly different price points (like for Effexor and Lyrica), they may have the less-expensive option on a lower tier, with the lowest copay. In the same vein, the more expensive options may be on a higher tier, with a higher copay.

Some plans may not cover the more expensive drug (Lyrica in this case) at all without what is known as a 'prior authorization'.

The prior authorization process requires your doctor to fill out paperwork and explain what therapies you have tried and the rationale behind why the drug in question should be covered. From there, the insurance company would make a determination on whether or not to cover the drug.

Yet another approach for insurance companies is to require 'step-therapy'. In this case, they would require you to try a less expensive drug option (but one that still has good evidence for effectiveness) before 'stepping-up' to a more expensive option. So, for you, it appears your insurance company is requiring you try Effexor before stepping up to Lyrica.

  • Elsevier ClinicalKey: Pregabalin (Accessed 1/25/19)
  • Elsevier ClinicalKey: Venlafaxine (Accessed 1/25/19)
  • Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care Journal (Accessed 1/25/19)
  • Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. PubMed (Accessed 1/25/19)
  • Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations. PubMed (Accessed 1/25/19)
  • Neuropathic pain: current definition and review of drug treatment. PubMed (Accessed 1/25/19)
  • Treatment Considerations for Patients With Neuropathic Pain and Other Medical Comorbidities. PubMed (Accessed 1/25/19)
  • Pharmacological Treatment Of Diabetic Peripheral Neuropathy. PubMed (Accessed 1/25/19)
  • Treatment Considerations for Patients With Neuropathic Pain and Other Medical Comorbidities. PubMed (Accessed 1/25/19)
  • Pharmacotherapy for diabetic peripheral neuropathy pain and quality of life: A systematic review. PubMed (Accessed 1/25/19)
  • Evaluation of the efficacy and safety of pregabalin, venlafaxine, and carbamazepine in patients with painful diabetic peripheral neuropathy. A randomized, double-blind trial. PubMed (Accessed 1/25/19)
  • A review of Neuropathic Pain: From Guidelines to Clinical Practice. PubMed (Accessed 1/25/19)

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