Despite limited evidence to support the use of tricyclic antidepressants (TCAs) and anticonvulsants for the treatment of vulvodynia, these medications have become mainstays of therapy for GVD and PVD (see Chapter 26). However, the common side effects of these medications, particularly the anticholinergic effects of the TCAs (e.g.,dry mouth, constipation) and the sedation and dizziness associated with gabapentin (an anticonvulsant), limit their clinical applicability.

For example, one placebo-controlled trial of the TCA amitriptyline, found that 92% of interstitial cystitis patients taking 100 mg or less experienced significant side effects, especially dry mouth [1]. Some vulvodynia experts believe that compounding amitriptyline and gabapentin into topical formulations has significant potential in the treatment of vulvar pain syndromes. Although optimal dosing and product stability have yet to be determined, trials to investigate and resolve these issues are planned.

Topical therapy can circumvent systemic side effects in at least two ways. First, the topical route of delivery reduces systemic absorption of the medication; second, the amount of active drug in topical preparations is significantly less than in oral medications. Although data on using topical agents with vulvar pain patients is sparse, studies of topical preparations in the treatment of other forms of chronic neuropathic pain suggest beneficial outcomes with minimal side effects. For example, in a trial of two commercially available topical medications, 5% doxepin and 0.025% capsaicin, overall pain scores were significantly reduced and side effects were minor, with only 15% of patients using topical doxepin experiencing drowsiness [2].

Many local therapies have shown promise in the treatment of vulvar pain disorders. In a number of case series and small uncontrolled trials, injectable interferon, injectable steroids and lidocaine, topical nitroglycerin, topical lidocaine, and topical capsaicin have shown some efficacy. Of the topical preparations, lidocaine, capsaicin, and nitroglycerin have all demonstrated promise as treatments for PVD.

Skin reactions to topical medications are not uncommon, and it is often the base of the cream, ointment, or gel that is to blame rather than the active ingredient. Thus, it is imperative to choose the proper vehicle when employing topical therapy, especially when it is to be applied to the sensitive vulvar skin/mucosa. Many topical formulations include well-known irritants, such as propylene glycol, or allergens, such as dibucaine. For patients with sensitivities to any of these ingredients, the use of a compounding pharmacy can be invaluable. The authors have found that acid mantle base and methylcellulose gel are generally very well tolerated. In addition, glycerin can replace propylene glycol as an emollient for women who are sensitive to the former. In general, ointments are better tolerated and often provide a protective barrier, whereas creams contain more preservatives and may cause burning on application.

Common reactions associated with topical anesthetics include stinging, erythema, and edema. Benzocaine, an anesthetic frequently found in over-the-counter topical preparations such as Vagisil^TM, should be avoided due to its association with allergic contact dermatitis. Patients should also realize that if an anesthetic is present on the skin during intercourse, their partners may experience numbness or side effects. Although the occurrence of serious reactions to topical formulations has not been well studied, they can occur with both lidocaine (e.g., double vision) and the tricyclic antidepressants (e.g., seizures, stroke, and myocardial infarction) [3].

Topical Therapy for Treatment of PVD and GVD

At present, there are no FDA-approved medications (systemic, topical, or injectable) for the treatment of vul-var pain symptoms. Many local therapies have shown promise in the reduction of vulvar pain symptoms in small case series and reports; however, placebo-controlled trials are lacking. When physicians on a referral list from the National Vulvodynia Association were surveyed regarding practice patterns, topical lidocaine was the most common first-line therapy for the treatment of PVD [4]. Based on its treatment efficacy (see below), this is certainly a reasonable and easily obtainable first choice of therapy.

To date, there are only two published randomized placebo-controlled trials on topical therapy for the treatment of PVD. In the first study, Nyirjesy et al. used 4% cromolyn sulfate cream to treat 26 recalcitrant PVD patients and found that placebo users were as likely to experience resolution of their pain as patients who used cromolyn [5]. In a second, small trial, Zyczynski et al. randomly assigned 14 vestibulitis patients to use either 0.025% cap-saicin or placebo five times a day for six weeks [6]. Of the nine women who completed the protocol, capsaicin users demonstrated a significant reduction in pain scores, as compared to those on placebo. Over the next 6 weeks, all patients were treated with capsaicin, and at the 12-week period, all reported similar pain relief, regardless of initial exposure.

Topical Anesthetics

Topical anesthetics, including lidocaine (2% jelly or 5% ointment; AstraZeneca Pharmaceuticals LP, Wilmington, DE), are the most commonly prescribed topical medications for the treatment of vulvar pain [3, 4]. Other topical anesthetics commonly employed include the following: EMLA (eutectic mixture of lidocaine and prilocaine, AstraZeneca, Wilmington, DE ) and LMX-4 (4% liposomal lidocaine, Ferndale Laboratories, Ferndale, MI). Benzocaine, apotent sensitizer found in severalover-the-counter agents including Vagisil (Combe, Inc., White Plains, NY) should not be used to treat vulvar pain.

In Zolnoun et al.’s trial of 5% lidocaine ointment in the treatment of 61 women with PVD, a significant increase in patients’ ability to have intercourse (76% vs. 36% at baseline) and a decrease in intercourse-related pain was found [7]. In this study, patients applied copious amounts of the ointment to a cotton-ball, which was then placed in the vestibule at bedtime. Patients performed this regimen nightly for an average of 7 weeks, although many continued to use the ointment at least sporadically in the following months. In another report, Danielsson et al. compared biofeedback and topical lidocaine gel in 46 women with PVD and found improved sexual functioning in both groups at 12 months [8].

Topical Capsaicin

Capsaicin is the purified extracted alkaloid from red chili peppers. Capsaicin selectively binds to TRPV1, a calcium channel in peripheral sensory nerve endings [9]. Prolonged activation of TRPV1 by capsaicin results in the depletion of substance P in the peripheral neurons leading to hypoathesia. Pain relief is not instantaneous, and repetitive application of capsaicin is required over weeks or months to cause depletion of substance P.

Topical capsaicin is available to treat neuropathic pain, and has shown efficacy in small studies, such as those conducted by Friedrich in 1988[10]and Zyczynski in 1997[6]. In a recent trial involving 52 women with PVD, Steinberg and colleagues instructed patients to use 0.025% capsaicin cream for 20 minutes each day[11]. After 12 weeks of treatment, women reported a significant decrease in discomfort and an increase in ability to have sexual intercourse (from 62% pretreatment to 95% following therapy). In this trial, however, some patients also needed topical lidocaine for pain control. Murina and colleagues also evaluated capsaicin 0.05% cream in 19 women, and while 59% noted improvement of symptoms, no complete remission was observed. Furthermore, severe burning was reported by all the women studied, and symptoms recurred after the use of capsaicin cream was discontinued [12]. Thus, Murina concluded that the use of capsaicin should be considered only as a “last-choice” medical approach. It should be noted that the concentration in the Murina study was twice the concentration used in the Steinberg study.