Postsurgical Gabapentin Use Increases Risk of Delirium, Antipsychotic Use and Pneumonia

Short-term pain management in the wake of surgery is essential for efficient physical and emotional recovery.[1] Current practice suggests that a multimodal approach (one that uses several methods) be used to cope with postsurgical pain, including localized treatments (for example, ice application and limb elevation), psychological approaches (for example, patient education and expectation-setting) and pharmacologic interventions, as needed.

Pharmacologic approaches also can be multimodal and commonly include nonsteroidal anti-inflammatory drugs such as ibuprofen (ADVIL, CALDOLOR, MOTRIN) or other non-opioid agents like acetaminophen (TYLENOL), and opioids for more severe bouts of pain. These drugs may be delivered intravenously or orally, and doses routinely are taken home to be used for a limited time after leaving the surgical facility.

The seizure medication gabapentin (GRALISE, NEURONTIN)[2] also is used to treat postsurgical pain, but that approach is controversial because of concerns about effectiveness and safety.[3]

A recent observational study examined gabapentin use to relieve pain immediately after major surgery and found that such use significantly increases the risk of delirium, antipsychotic use and pneumonia in the postsurgical period.

Background on gabapentin

Worst Pills, Best Pills News has published several articles about gabapentin, most cautioning the public about the drug’s overuse and numerous adverse effects, including failed effectiveness,[4] breathing problems,[5] driving impairment,[6] drowsiness, depression,[7] movement disorders,[8] weight gain[9] and even overdose death.[10]

Despite such concerns, gabapentin — originally approved for one type of epilepsy and later approved for postherpetic neuralgia (lingering pain following a shingles infection) — has become widely used for many other indications, including the treatment of postsurgical pain. The safety and effectiveness data for these off-label indications for gabapentin, however, are poor, making such uses of the drug controversial.[11],[12]

The new observational study[13]

The recent study, which was published in the November 2022 issue of the Journal of the American Medical Association Internal Medicine, used a large health care database to examine gabapentin use for pain during the perioperative period (the day of surgery and continuing until hospital discharge). This study focused on older adults (average age of 76 years) and considered whether gabapentin use increased their risk of delirium as a primary outcome and new antipsychotic drug use, pneumonia and death as secondary outcomes.

The database used for this study contained records corresponding to hospital-based events that occurred in over 900 small-to-medium-sized facilities, reflecting the experiences of approximately 25% of all inpatient hospitalizations in the U.S.

From that database, the following subpopulation was selected to form the analytic sample for this study: persons over 65 years of age who underwent a major surgical procedure within seven days of hospital admission between 2009 and 2018 and who survived at least two days after surgery without the need for mechanical ventilation or a feeding tube. Major procedures included cardiac, gastrointestinal, genitourinary, orthopedic, thoracic and vascular surgeries. Surgeries involving the brain were excluded. Other exclusions were made if the patient had a history of antipsychotic treatment, psychosis or possible gabapentin use prior to the surgery. These criteria identified 967,547 surgical patients qualifying for the study, including 119,087 older adult patients exposed to gabapentin during the perioperative period.

Nearly all (118,936; 99.8%) of the gabapentin-exposed patients were statistically matched to the same number of non-exposed patients based on the following important factors: demographics, insurance type, admission characteristics, surgery type, comorbidities (other illnesses), other medication use (including opioids), hospital characteristics and calendar year of the surgery. Summary results appear in the Table below and clearly show that perioperative gabapentin exposure elevates the risk of postsurgical delirium, new antipsychotic use and pneumonia.

Count (and Percent) of Adverse Events Related to Perioperative Gabapentin Use

†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***The 80-milligram dose of simvastatin is designated as Do Not Use.

In their discussion regarding this study of gabapentin use, the researchers make two important points. First, they note that the collective results from over 200 randomized clinical trials indicate that perioperative gabapentin pain control is generally “inconsistent and not clinically meaningful.” Second, they note the existence of at least two published meta-analyses demonstrating that postoperative gabapentin use only weakly reduces the need for opioid pain relief.

What You Can Do

Prior to any major surgeries, make sure that your doctors (including your anesthesiologist) know if you are taking gabapentin or the related drug pregabalin (LYRICA). Furthermore, make sure that your doctors are aware of all the medications you are taking. Also, regardless of your medication use leading up to the surgery, try to avoid the use of gabapentin to cope with the pain that often follows a surgical procedure.
 

References

[1] Mariano ER. Approach to the management of acute pain in adults. UpToDate. January 19, 2023.

[2] ACI Healthcare. Label: Gabapentin. January 2023. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7538e255-95df-4991-aae0-a90d709f1e95&type=display. Accessed April 4, 2023.

[3] Mariano ER. Approach to the management of acute pain in adults. UpToDate. January 19, 2023.

[4] Worst Pills, Best Pills News. New research shows gabapentin not effective for pelvic pain in women. March 2021. https://www.worstpills.org/newsletters/view/1388. Accessed April 4, 2021.

[5] Worst Pills, Best Pills News. FDA warns of serious breathing problems with use of gabapentin and pregabalin. April 2020. https://www.worstpills.org/newsletters/view/1327. Accessed April 4, 2023.

[6] Worst Pills, Best Pills News. Driving under the influence caused by medication. September 2020. https://www.worstpills.org/newsletters/view/1355. Accessed March 24, 2020.

[7] Worst Pills, Best Pills News. New research shows drugs associated with a risk of depression are widely used. October 2018. https://www.worstpills.org/newsletters/view/1223. Accessed April 4, 2018.

[8] Worst Pills, Best Pills News. Drug-induced movement disorders. February 2018. https://www.worstpills.org/newsletters/view/1179. Accessed April 4, 2023.

[9] Worst Pills, Best Pills News. Drugs that cause weight gain. December 2017. https://www.worstpills.org/newsletters/view/1167. Accessed April 4, 2023.

[10] Worst Pills, Best Pills News. FDA warns of serious breathing problems with use of gabapentin and pregabalin. April 2020. https://www.worstpills.org/newsletters/view/1327. Accessed April 4, 2023.

[11] Worst Pills, Best Pills News. Gabapentinoid drug use is exploding despite poor safety and efficacy profiles. October 2020. https://www.worstpills.org/newsletters/view/1358. Accessed April 4, 2023.

[12] Mariano ER. Approach to the management of acute pain in adults. UpToDate. January 19, 2023.

[13] Park CM, Inouye SK, Marcantonio ER, et al. Perioperative gabapentin use and in-hospital adverse clinical events among older adults after major surgery. JAMA Intern Med. 2022;182(11):1117-1127.