Is there data to support vaginal administration of commercial diazepam tablets for pelvic floor dysfunction?

Comment by InpharmD Researcher

There appears to be a paucity of data to support vaginal administration of commercial diazepam tablets for pelvic floor dysfunction. Our comprehensive literature search identified one retrospective review of 21 women with pelvic floor dysfunction who elected to use oral diazepam tablets intravaginally rather than compounded formulations (Table 1). After one month, 62% reported moderate or marked improvement with reduced pain scores, and serum diazepam concentrations remained within the therapeutic range. While the findings suggest potential benefit, the evidence remains preliminary and limited by small sample size and lack of controlled data.

Background

A 2020 systematic review evaluated intravaginal diazepam for chronic pelvic pain and sexual dysfunction associated with high-tone pelvic floor dysfunction. A total of five investigations met inclusion criteria (two observational studies and three small randomized controlled trials [RCTs]). The observational studies reported subjective improvements in sexual function in most patients, but no significant changes in Female Sexual Function Index (FSFI) or Visual Analog Scale (VAS) scores. The RCTs were largely negative, with one showing benefit only when diazepam was combined with transcutaneous electrical nerve stimulation. Additionally, limited pharmacokinetic data suggested systemic absorption within therapeutic ranges. Of note, this review did not specifically discuss the use of commercial oral diazepam tablets for intravaginal administration in pelvic floor dysfunction. However, the authors referenced one study where patients were offered either compounded diazepam cream or suppositories, but all elected to use oral diazepam tablets intravaginally (see Table 1 and Carrico et al., summarized below for specific study details). [1]

A 2011 retrospective review (Table 1) evaluated the efficacy and serum levels of vaginal diazepam for the management of pelvic floor dysfunction and urogenital pain in a cohort of 21 women treated over one month. Options for care were reviewed with the patient, including the off-label use of vaginal diazepam. The discussion covered potential risks, benefits, and side effects for both the patient and her sexual partner. Vaginal diazepam was prescribed at a dose of 2-10 mg, to be used as needed for symptom relief up to every 8 hours. The typical starting dose was 5 mg, with a lower starting dose of 2 mg for women reporting heightened sensitivity to medications. If 5 mg did not provide relief after 7-10 days and the dose was tolerated, it could be increased to 10 mg. Notably, patients were offered the option of a compounded vaginal cream or suppository, but all chose to use the oral tablet vaginally first. Instructions allowed insertion of the tablet either whole or crushed and mixed with vaginal lubricant. Pain levels were documented weekly using a VAS pain score, and serum diazepam levels were measured in 15 women who used the medication daily. Following one month of treatment, 62% of participants reported moderate or marked improvement, while 71% believed vaginal diazepam was beneficial. Mean overall pain scores decreased from 4.8 to 3.4 on a 10-point scale, while vulvar pain and levator examination pain scores were similarly reduced. Serum diazepam levels remained within the normal therapeutic range (mean level 0.29 mcg/mL; reference range 0.02–1.0 mcg/mL), and only 33% of participants experienced mild drowsiness. The findings suggested that vaginal diazepam may offer symptom relief for pelvic floor hypertonicity-related pain while avoiding the systemic side effects commonly associated with oral benzodiazepines. However, the investigators highlighted the need for larger RCTs to validate these preliminary observations. [2]

References:

[1] Stone RH, Abousaud M, Abousaud A, Kobak W. A Systematic Review of Intravaginal Diazepam for the Treatment of Pelvic Floor Hypertonic Disorder. J Clin Pharmacol. 2020;60 Suppl 2:S110-S120. doi:10.1002/jcph.1775
[2] Carrico DJ, Peters KM. Vaginal diazepam use with urogenital pain/pelvic floor dysfunction: serum diazepam levels and efficacy data. Urol Nurs. 2011;31(5):279-299.
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there data to support vaginal administration of commercial diazepam tablets for pelvic floor dysfunction?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Table 1 for your response.

 

Vaginal Diazepam Use with Urogenital Pain/Pelvic Floor Dysfunction: Serum Diazepam Levels and Efficacy Data
Design

Retrospective chart review

N= 21
Objective To describe the serum diazepam levels and efficacy of the off-label use of vaginal diazepam for pelvic floor dysfunction pain, PBS/IC, and/or vulvar pain in a clinic population
Study Groups All patients (n= 21)
Inclusion Criteria Women with vulvar pain on their Q-Tip® examination or with levator pain on examination who were treated with off-label vaginal diazepam
Exclusion Criteria Not specified
Methods

21 women were evaluated for overall, levator, and vulvar pain pre- and one-month post-daily diazepam treatment. Patients were counseled on care options, including off-label vaginal diazepam, with discussion of potential risks, benefits, and side effects for themselves and their sexual partners. With informed verbal consent, vaginal diazepam was prescribed at 2–10 mg as needed, up to every 8 hours. The usual starting dose was 5 mg, with 2 mg for women sensitive to medications; if 5 mg was ineffective after 7-10 days and tolerated, the dose could be increased to 10 mg. Patients were offered a compounded vaginal cream or suppository, but all chose to use the oral tablet vaginally, either whole or crushed with lubricant. Serum diazepam levels were measured. 
Duration One month post-treatment
Outcome Measures Serum diazepam levels, efficacy of pain reduction, patient self-reports of pain improvement, and adverse effects
Baseline Characteristics   All patients (n= 21)
Mean age, years (range) 40 (22 to 61)
PBS/IC diagnosis 4 (19%)
Vulvodynia diagnosis 9 (42.8%)
Pelvic floor dysfunction 7 (33.3%)
Results   Pre-Diazepam VAS Post-Diazepam VAS
Overall Pain (n= 21) 4.8 ± 2.5 3.4 ± 2.5
Vulvar Pain (n= 11) 5.9 ± 7.6  2.2 ± 1.7 
Levator Pain (n= 19) 3.8 ± 3.2 1.8 ± 2.1

62% percent of participants reported moderate or marked improvement, and 71% believed vaginal diazepam was “helping,” while 24% reported it “sometimes” helped. One participant reported no change, and none worsened.

71% of women used vaginal diazepam daily and had serum diazepam levels measured one month after starting treatment. Levels were within the normal therapeutic range (0.20-1.00 mcg/mL), ranging from <0.1 to 0.7 mcg/mL, with a mean of 0.29 mcg/mL. The highest level, 0.7 mcg/mL, was measured two hours after a 5 mg dose. A woman taking 10 mg three times daily for one month had a serum level of 0.16 mcg/mL.
Adverse Events 33% reported mild drowsiness; no serious adverse effects reported.
Study Author Conclusions Vaginal diazepam may be helpful in treating pelvic floor/urogenital pain conditions. Larger, randomized-controlled research trials are needed.
Critique The study is limited by its small sample size and lack of a control group. The retrospective design and use of a non-validated home recording form limit the generalizability of the findings. However, the study provides preliminary data suggesting the potential efficacy of vaginal diazepam for pelvic floor dysfunction pain, warranting further investigation in larger, controlled trials.
References:

Carrico DJ, Peters KM. Vaginal diazepam use with urogenital pain/pelvic floor dysfunction: serum diazepam levels and efficacy data. Urol Nurs. 2011;31(5):279-299.