Treatment of Levator Ani Syndrome with Cyclobenzaprine

C ASE REPORTS Treatment of Levator Ani Syndrome with Cyclobenzaprine Maheen Sheikh, Crystal A Kunka, and Ken S Ota evator ani syndrome (LAS) is a significant clinical pain syndrome that is thought to be secondary to levator ani muscle spasms. The pain from LAS is chronic and recurring, with each episode lasting approximately 20 minutes.1 Most patients report vague tenderness or aching in the rectum, which is worse with defecation and sitting and alleviated when ambulating and lying down. A review of the literature reveals that definitive treatment options for LAS are limited. We report the successful treatment of a patient with LAS with a 1-week course of cyclobenzaprine. L Case Report OBJECTIVE: To report a case of levator ani syndrome (LAS) that was successfully treated with cyclobenzaprine. CASE SUMMARY: A 26-year-old male presented with a 3-week history of severe, intermittent, aching anorectal pain that would last for 30-60 minutes per episode and occurred between 1 and 3 times per day. The pain was aggravated by squatting, with no alleviating factors. Physical examination revealed no prostate tenderness, lesions, hemorrhoids, or fissures and rectal tone was intact. The patient had moderate posterior rectal tenderness. After a standard workup, he was diagnosed with LAS and treated with oral cyclobenzaprine 5 mg 3 times daily for 7 days. The patient experienced resolution of his symptoms after 3 days of treatment and remained symptom-free 6 months after completion of therapy. The only reported adverse effect was mild drowsiness, which resolved after discontinuation of the cyclobenzaprine. DISCUSSION: A review of the literature via StatRef (April 1965-December 2011), Ovid (April 1965-December 2011), and MEDLINE (April 1965-December 2011) reveals that existing treatment options for LAS have been limited to levator massage, sitz baths, nonsteroidal antiinflammatory drugs, diazepam, biofeedback, botulinum toxin, steroid injections, and electrogalvanic stimulation, all of which offer minimal support. Cyclobenzaprine is a muscle relaxant; however, its mechanism of action is unclear. It is thought to influence the α and γ motor neurons in the central nervous system, which leads to the attenuation of muscle spasm. To our knowledge, cyclobenzaprine has not been reported as a treatment for LAS. In our patient, however, the clinical efficacy of cyclobenzaprine was clearly apparent. A 26-year-old male presented with a 3-week history of severe, intermittent, aching pain in the rectum lasting for 3060 minutes, occurring between 1 and 3 CONCLUSIONS: Cyclobenzaprine effectively treated our patient’s LAS. Given that times per day. He stated that he had the cyclobenzaprine is safe, inexpensive, and shown to be effective in our case same clinical presentation approximately study, we believe it warrants further investigation as a first-line treatment option 9 months prior, which resolved without for LAS. intervention after 2 days of watchful KEY WORDS: anorectal pain, cyclobenzaprine, levator ani syndrome. waiting. The pain was aggravated by sitAnn Pharmacother 2012;46:e29. ting or squatting and was severe enough Published Online, 18 Sept 2012, theannals.com, doi: 10.1345/aph.1R144 to keep him from performing his occupation as a mechanic. Prior to his presentation the patient had tried over-theness, constipation, or diarrhea. He reported eating a reacounter nonsteroidal antiinflammatory drugs, with no resonably healthy diet, denied drug or tobacco use, and delief. The patient denied dyschezia, hematochezia, rectal scribed himself as a “social” drinker (2-3 beers per weektrauma, rectal fullness, coccygeal pain, back pain, weakend). He reported no regular medications, previous surgery, or significant family history. Results of a depresAuthor information provided at end of text. sion screening were negative. theannals.com The Annals of Pharmacotherapy ■ 2012 October, Volume 46 ■ e29 M Sheikh et al. On physical examination, the patient’s vital signs were within normal limits. Results of abdominal and genitourinary examinations were benign. Rectal examination revealed no prostate tenderness, lesions, hemorrhoids, or fissures. Rectal tone was intact, with moderate posterior rectal tenderness. Buttocks were without muscle atrophy or loss of sensation. Anoscopy was performed and revealed no remarkable findings and computed tomography scan of the pelvis revealed absence of perirectal pathology. The patient was ultimately diagnosed with LAS. Empiric cyclobenzaprine 5 mg 3 times per day for 1 week was started in an attempt to induce relaxation of the levator ani muscles. The patient reported decreased frequency and intensity of muscle spasms within the first 24 hours of treatment. Symptom resolution was achieved by the third day of treatment and the cyclobenzaprine was continued for 1 full week. Follow-up at 2 and 6 months revealed no further episodes of rectal pain. The patient’s only reported adverse effect was drowsiness while taking cyclobenzaprine, which resolved after discontinuation. Epidemiology and Diagnosis of Levator Ani Syndrome LAS is a functional anorectal pain syndrome that is more common in women than in men.2 Most patients are diagnosed between the ages of 30 and 60 years; however, the overall prevalence is low, at 6.6% in the general population.2-4 It is estimated that only 29% of patients with LAS report their symptoms to a physician.5 According to a 1993 postal survey of 5430 adults, 17.9 work days per year have reportedly been missed due to symptoms of LAS.6 Diagnosis is based on history and physical examination and may be categorized as highly likely, where patients have both symptomatic criteria and physical signs, or possible, with symptom criteria but absent physical signs.5 Diagnostic criteria are outlined by the Rome III Criteria2 and include tenderness with posterior traction of the puborectalis plus all of the following: (1) chronic or recurrent rectal pain or aching, (2) episodes lasting 20 minutes or longer, and (3) absence of other causes of rectal pain, including rectal ischemia, inflammatory bowel disease, cryptitis, intramuscular abscess, fissure, hemorrhoids, prostatitis, and solitary rectal ulcer. The symptoms must be present for the past 3 months, with symptom onset more than 6 months prior to diagnosis. Literature Review and Discussion A literature search via StatRef (April 1965-December 2011), Ovid (April 1965-December 2011), and MEDLINE (April 1965-December 2011) was performed and we found multiple publications that discussed currently available treatment options for LAS. These treatments included e29 ■ The Annals of Pharmacotherapy ■ biofeedback, electrogalvanic stimulation (EGS), sitz baths, diazepam, botulinum toxin, steroid injections, nonsteroidal antiinflammatory drugs, and digital massage.4,7-11 We found no studies that examined the use of cyclobenzaprine for the treatment of LAS. Studies on the effect of EGS showed mixed results.8,12,13 In 1985 Nicosia and Abcarian8 reported that EGS provided total relief of pain in 80% (36/45) of patients. However, long-term follow-up was lacking and, therefore, in 1993 Hull et al.12 performed a long-term study evaluating EGS for LAS, which concluded that EGS does not produce acceptable results over a mean follow-up period of 28 months. Long-term follow-up revealed that 57% of patients reported no benefit from EGS and therefore did not provide substantial long-term benefit. Furthermore, EGS requires multiple visits and is time consuming and invasive. Heah et al.7 examined the results of biofeedback in 16 patients. Biofeedback was conducted for 1 hour once per week for 4 weeks and patients reported a decrease in both the level of pain and need for analgesia. Follow-up at 2 and 4 years showed no regression of symptoms or adverse effects. The drawback of biofeedback is that it is time consuming; nevertheless, it has no harmful effects and is worth offering to patients as a treatment option. Chiaroni et al. conducted a prospective, randomized controlled trial comparing the efficacy of biofeedback, EGS, or massage.14 Results found that biofeedback was the most effective treatment, whereas EGS was somewhat effective. Park et al.15 hypothesized that LAS may be due to tendonitis of the arcus tendon of the levator ani muscles. In their study, triamcinolone/lidocaine injections were compared to EGS at a rate of 2 sessions per week. Follow-up at 12 months revealed greater anorectal pain relief in the injection group. These patients, however, reported that a sufficient level of patient satisfaction was not achieved. Ng16 reported a patient diagnosed with LAS that was treated with diazepam and sitz baths. It was reported that the patient’s pain resolved after 2 days of diazepam and sitz bath treatment. This case report lacks further follow-up data. Moreover, diazepam must be used with caution because of its addictive potential. Salvati11 discussed digital massage of the anterior and posterior walls of the rectum as a treatment option for LAS. This treatment may be technically difficult to do and patients may not be amenable to the intervention. Moreover, digital massage has not been shown to be effective. Surgical division of the puborectalis muscle has been described as a method of treatment for functional anorectal pain.17 A high incidence of postoperative liquid and gas incontinence has been observed; therefore, surgery should not be recommended as an option for functional anorectal pain. 2012 October, Volume 46 theannals.com Treatment of Levator Ani Syndrome with Cyclobenzaprine Rao et al.10 conducted a placebo-controlled trial of botulinum toxin in the treatment of 12 patients with LAS. Intrasphincteric injections were given at 90-day intervals and patients noted no change from baseline in the intensity or duration of anorectal pain. In our case we treated the patient with oral cyclobenzaprine 5 mg 3 times daily for 7 days and his symptoms resolved by day 3 of treatment. This dose was chosen because it is a common initial dosing regimen for skeletal muscle spasm. Unlike other muscle relaxants that have pharmacologic activity at the neuromuscular junction, cyclobenzaprine acts at the brain stem and influences γ and α motor neurons.18 Bioavailability of the immediate-release tablets is between 33% and 55%, with a time to peak effect of approximately 4 hours. Common adverse effects include dry mouth, somnolence, and dizziness. Although our patient experienced somnolence during his treatment period, he believed that it was a tolerable adverse effect in light of resolution of his anorectal pain. Although there is a paucity of evidence-based treatments for LAS, primary care physicians should be aware of this pain syndrome. Current studies published in the medical literature do not provide consistent results. In our patient, treatment with cyclobenzaprine resulted in resolution of symptoms in 3 days, with no recurrence on followup at 2 and 6 months. The reason why cyclobenzaprine had such a prolonged effect on this patient is unclear. It is plausible that other outside factors that were not brought to the physician’s attention at the time of presentation (ie, psychosocial stress) may have triggered his symptoms of LAS. However, in this retrospective analysis we cannot offer a definitive explanation for the efficacy of the treatment regimen. In the event the patient has a relapse of LAS, we recommend repeat treatment with cyclobenzaprine. Although cyclobenzaprine is relatively safe and inexpensive, patients should be warned about somnolence, which is a common adverse effect of this medication. Our patient’s anorectal pain improved after taking cyclobenzaprine for 3 days; however he was maintained on this medication for 7 days due to the treating physician’s discretion and concern for immediate relapse of symptoms. In retrospect, we believe that discontinuing therapy on the day of symptom resolution would have been reasonable and appropriate. In summary, although our patient had complete resolution of his LAS symptoms, this is a single case report and we contend that further investigation of cyclobenzaprine as a first-line treatment for LAS is warranted. Given that this pharmacologic agent is inexpensive, safe, and was demonstrated to be effective in our patient, we believe it warrants further investigation as a first-line treatment option for LAS. theannals.com Maheen Sheikh MD, Resident, PGY-3, Department of Internal Medicine, Banner Good Samaritan Medical Center, Phoenix, AZ Crystal A Kunka DO, Resident, PGY-2, Department of Family Medicine, Scottsdale Healthcare, Scottsdale, AZ Ken S Ota DO, Transitionalist, Department of Transitional Care Medicine, Banner Good Samaritan Medical Center Correspondence: Dr. Sheikh, [email protected] Reprints/Online Access: www.theannals.com/cgi/reprint/aph.1R144 Conflict of interest: Authors reported none References 1. Marcello P. Unexplained anal pain. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology/diagnosis/management. Philadelphia: Saunders, 2010: 2272-3. 2. Bharuch AE, Trabuco E. Functional and chronic anorectal and pelvic pain disorders. Gastroenterol Clin North Am 2008;37:685-96. 3. Bharuch AE, Wald A, Erick P, Rao S. Functional anorectal disorders. Gastroenterology 2006;130:1510-8. 4. Wald A. Functional anorectal and pelvic pain. Gastroenterol Clin North Am 2001;30:243-51. 5. Whitehead WE, Wald A, Diamant NE, Enck P, Pemberton JH, Rao SSC. Functional disorders of the anus and rectum. Gut 1999;45:1155-9. 6. Drossman DA, Li Z, Andruzzi E, Temple RD, Talley NJ, Thompson WG, et al. U.S. household survey of functional gastrointestinal disorders. Prevalence, sociodemography and health impact. Dig Dis Sci 1993;38: 1569-80. 7. Heah SM, Ho YH, Tan M, Leong AF. Biofeedback is effective treatment for levator ani syndrome. Dis Colon Rectum 1997;40:187-9. 8. Nicosia JF, Abcarian H. Levator syndrome. A treatment that works. Dis Colon Rectum 1985;28:406-8 9. Dodi G, Bogoni F, Infantino A, Pianon P, Mortellaro LM, Lise M. Hot or cold in anal pain? A study of changes in internal anal sphincter pressure profiles. Dis Colon Rectum 1986;29:248-51. 10. Rao SS, Paulson J, Mata M, Zimmerman B. Clinical trial: effects of botulinum toxin on levator ani syndrome—a double blind, placebo controlled study. Aliment Pharmacol Ther 2009;29:985-91. 11. Salvati EP. The levator syndrome and its variant. Gastroenterol Clin North Am 1987;16:71-8. 12. Hull TL, Milsom JW, Church J, Oakley J, Lavery I, Fazio V. Electrogalvanic stimulation for levator syndrome: how effective is it in the longterm? Dis Colon Rectum 1993;36:731-3. 13. Morris L, Newton RA. Use of high voltage pulsed galvanic stimulation for patients with levator ani syndrome. Phys Ther 1987;67:1522-5. 14. Chiarioni G, Nardo A, Vantini I, Romito A, Whitehead WE. Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levator ani syndrome. Gastroenterology 2010;138:1321-9. 15. Park DH, Yoon SG, Kim KU, et al. Comparison study between electrogalvanic stimulation and local injection therapy in levator ani syndrome. Int J Colorectal Dis 2005;20:272-6. 16. Ng CL. Levator ani syndrome—a case study and literature review. Aust Fam Physician 2007;36:449-52. 17. Barnes PRH, Hawley PR, Preston DM, Lennard-Jones JE. Experience of posterior division of the puborectalis muscle in the management of chronic constipation. Br J Surg 1985;72:475-7. 18. Cyclobenzaprine. Drugdex. Version 5.1 Greenwood Village, CO: Thomson Reuters (Healthcare) Inc. The Annals of Pharmacotherapy ■ 2012 October, Volume 46 ■ e29