New Research Shows Gabapentin Not Effective for Pelvic Pain in Women

Gabapentin (NEURONTIN, HORIZANT, GRALISE) is a gabapentinoid drug currently approved to treat focal (partial) seizures, postherpetic neuralgia (long-term pain that occurs as a late complication of shingles) and restless legs syndrome.[1],[2],[3] Public Citizen’s Health Research Group designates this medication as Limited Use for focal (partial) seizures and postherpetic neuralgia and recommends that the drug not be used for other conditions, including restless legs syndrome.[4]

Gabapentin is frequently prescribed for uses not approved by the Food and Drug Administration (so-called off-label uses), especially for chronic pain. A recently published clinical trial underscores why such off-label use, which we oppose, should be avoided.

Pelvic pain treatment study

A study of gabapentin as a treatment for chronic pelvic pain in women was published in the journal Lancet on Sept. 26, 2020.[5] Gabapentin has been considered as a potential treatment for pelvic pain because of the drug’s “perceived effectiveness” in treating other types of chronic pain.

Prior research has found that noncyclic (not connected to dysmenorrhea [menstruation pain] or dyspareunia [pain related to sexual intercourse]), chronic or intermittent pelvic pain occurred in 15% of women in the U.S. and 24% of women in the U.K.[6]

For the Lancet study, researchers in the U.K. enrolled 306 women with at least three months of pelvic pain (with or without dysmenorrhea or dyspareunia) and randomly assigned them to receive oral gabapentin capsules or a placebo once daily (153 in each group). Women who only had dysmenorrhea-related (cyclical) pelvic pain were excluded from the study. The initial dosage of gabapentin was one 300-milligram (mg) capsule once daily. Over the first four weeks, the daily dose was increased every three days by one capsule until the subject perceived adequate pain relief or reported unacceptable side effects, up to a maximum of nine capsules (2,700 mg). The subjects were followed for 16 weeks after the initial treatment dose.

Importantly, the gabapentin- and placebo-group subjects were well-balanced at baseline (before starting gabapentin or placebo) with respect to the following characteristics, among others: age, ethnicity, education level, body mass index (a measure of total body fat based on weight and height), proportion experiencing dysmenorrhea, scores on standardized measures of anxiety and depression, and use of sex hormones and other analgesic medications, including opioids.

There were two main outcomes for this study, obtained directly by self-report from the subjects: average pain scores and maximum pain scores. Both outcomes were assessed using a 10-point scale where “0” indicated “no pain” and “10” indicated “worst pain imaginable.” At baseline, average pain scores were 5.5 for both groups, and the maximum pain scores were an average of 8.4 for the gabapentin group and 8.6 for the placebo group. At the end of the 16-week treatment period, average pain scores and maximum pain scores had dropped on average by about one point in both the gabapentin and placebo groups, with no statistically significant differences in the declines between the two groups.

Adverse effects were more frequent in the gabapentin-group subjects than in the placebo-group subjects. In particular, dizziness (54% versus 28%), drowsiness (52% versus 29%) and visual disturbances (22% versus 11%) were all significantly more common in the gabapentin-group subjects than placebo-group subjects, respectively. Moreover, adverse events classified as “serious” were also significantly more likely in the gabapentin-group subjects (7% versus 2%).

The Lancet study researchers compared their adverse-effect findings with those of previous research evaluating gabapentin for chronic pain and thereby confirmed their observations. In particular, prior randomized clinical trials testing gabapentin as a treatment for postherpetic neuralgia and pain due to diabetic neuropathy (diabetes-related nerve damage) showed that the drug also caused significant increases in drowsiness and dizziness compared with a placebo. They further noted that use of gabapentin is associated with an increased risk of suicidal behavior and substance misuse.

The overall results led the Lancet study researchers to “confidently conclude that gabapentin is not effective for chronic pelvic pain in women” and that “no further research is required” for this treatment. This strong conclusion was placed in the context of previous research on gabapentin treatment for chronic pelvic pain, which included only two randomized clinical trials. Both previous trials were small, and one was open-label (unblinded) and compared gabapentin to an antidepressant rather than a placebo. These prior trials thus were not as well-designed or informative as the new Lancet study.

What You Can Do

If you are a woman suffering from chronic pelvic pain, do not use gabapentin as a remedy for that condition. Instead, seek physical therapy and psychotherapeutic approaches and, as necessary, alternative pain medications.
 

References

[1] Pfizer. Label: gabapentin (NEURONTIN). April 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021446s040,%20022488s017lbl.pdf. Accessed January 8, 2021.

[2] Almatica Pharma. Label: gabapentin (GRALISE). April 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022544s026lbl.pdf. Accessed January 8, 2021.

[3] Arbor Pharmaceuticals. Label: gabapentin (HORIZANT). April 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022399s010lbl.pdf. Accessed January 8, 2021.

[4] Gabapentinoid drug use is exploding despite poor safety and efficacy profiles. Worst Pills, Best Pills News. October 2020. /newsletters/view/1358. Accessed January 8, 2021.

[5] Horne AW, Vincent K, Hewitt CA, et al. Gabapentin for chronic pelvic pain in women (GaPP2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2020:26;396(10255):909-917.

[6] Latthe P, Latthe M, Say L, et al. WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity. BMC Public Health. 2006;6(6):177.