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Gabapentin or Pregabalin? Or Neither?

In the setting of neuropathic pain, clinicians need to determine whether a gabapentinoid

September 14, 2020
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Dr. Robert Hall

In the setting of neuropathic pain, clinicians need to determine whether a gabapentinoid (gabapentin or pregabalin) or a tricyclic antidepressant (e.g., amitriptyline or nortriptyline) should be the initial choice of therapy. If there are no contraindications (e.g., cardiac disease, glaucoma, urinary retention), tricyclic medications should be the preferred choice because they are more effective and less expensive. According to Colorado’s Division of Workers’ Compensation (DOWC) Medical Treatment Guidelines, dosing of any neuropathic pain medication should begin with the lowest effective dose demonstrated to be useful for neuropathic pain. Dosage adjustments should then be made based on response and tolerability.

If tricyclics do not produce sufficient therapeutic benefit, gabapentinoids are a reasonable second-line option. Gabapentinoids are FDA-approved and often effective for the treatment of a variety of neuropathic pain disorders. They can also reduce the need for opioid therapy. On the other hand, they are ineffective in the treatment of nociceptive pain caused by conditions such as osteoarthritis and soft tissue injuries. Gabapentinoids also pose safety risks. Therefore, when considering whether to prescribe gabapentin or pregabalin for pain relief, the type of injury and the patient’s risk profile should be considered.

The DOWC Medical Treatment Guidelines elaborate on these points, specifying, for example, that gabapentinoids are inappropriate for low back pain and cumulative trauma conditions. Clinicians who prescribe these medications should monitor patients for potential suicidal ideation. Clinicians should also be aware of the abuse potential of these medications; pregabalin carries a Drug Enforcement Agency (DEA) Schedule V classification, and there are documented cases of gabapentin abuse. Gabapentinoids taken with opioids, with other CNS depressants (including tricyclics) or against a background of respiratory conditions such as chronic obstructive pulmonary disease, can increase the risk of respiratory depression. Finally, because both drugs can cause withdrawal symptoms when suddenly discontinued or when doses are dramatically reduced, they should be tapered before discontinuation.

While both gabapentin and pregabalin share a similar mechanism of action, pregabalin is absorbed more rapidly and has a greater bioavailability. Both drugs are excreted renally, with each drug requiring dosing adjustments for patients with kidney dysfunction. From a financial standpoint, pregabalin’s generic availability has led to significantly decreased costs. In many cases, the twice daily dosing of pregabalin has made it more economical than gabapentin, which is usually prescribed in three daily doses.

Careful selection and monitoring of the medication options can minimize risks to the injured worker and achieve effective pain relief.  


Colorado Department of Labor and Employment Division of Workers’ Compensation. (2017, October 6). Chronic Pain Disorder Medical Treatment Guideline.

Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661-669.

Buscaglia, Brandes, & Cleary. (2019, July 19). The Abuse Potential of Gabapentin & Pregabalin. Practical Pain Management.

U.S. Food and Drug Administration. FDA Drug Safety Communication. (2019, December 19). FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) when used with CNS depressants or in patients with lung problems.

Author’s note for PREFACE:

As medical director at Optum Workers’ Compensation and Auto No-Fault, Dr. Robert Hall advises customers and employees on evidence-based clinical and rehabilitation guidelines to optimize pharmacy, home health and durable medical equipment programs in order to promote better outcomes for claimants. Dr. Hall is a practicing, board-certified physical medicine and rehabilitation physician.

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