Archive for June 30, 2008

IC & Hydroxyzine

June 30, 2008 · Filed under Interstitial Cystitis

 

IC & Hydroxyzine
Drug Information
Hydroxyzine is an antihistamine and mild anti-anxiety drug. It affects mast cell degranulation, which is thought to play a part in some interstitial cystitis (IC) patients’ symptoms, especially those who have a history of allergies, migraines and irritable bowel syndrome. Hydroxyzine has been shown to improve these conditions, as well as IC.

Hydroxyzine has been found to:

  • decrease nocturia (night time voiding)
  • decrease daytime frequency
  • decrease pain (burning, pressure, painful intercourse)

Hydroxyzine is available in the following two oral forms:

  • Generic name: hydroxyzine pamoate
    Brand name: Vistaril®
  • Generic name: hydroxyzine hydrochloride
    Brand name: Atarax®

Hydroxyzine pamoate (Vistaril) has a slightly higher absorption rate. Hydroxyzine-HCL is a liquid form available for patients allergic to fillers or dyes used in the capsules or pills.
 
Dosage
Most patients start with a 10 to 25 mg dosage of Atarax, Vistaril or their generic equivalent at bedtime every night for 1 week, and progress to 50 mg every night the second week. Ideally, within one month the dosage is increased to 75 mg, 50 mg taken at night and 25 mg taken during the day. Benefits of hydroxyzine may be seen within a few weeks to two months after initiating therapy. To decrease the sedating side effects, some patients start hydroxyzine therapy at a 10 mg dosage, available with Atarax or in the liquid form, and work their way up, gradually, to a maximum dosage of 50 – 75 mg After one year some patients are able to decrease their dosage by one-half without increasing symptoms. Others report that upon reducing their dosage, symptoms will return within a few days.

Side Effects

  • sedation
  • dry mouth
  • increased depression in patients diagnosed with concurrent depression

Self-Help Strategies
Take this medication early in the evening initially to avoid excessive morning drowsiness. Keep in mind that most patients report that any daytime drowsiness disappears within four to five days after beginning hydroxyzine therapy. Some patients report that with each dosage increase, the drowsiness period is shorter and not as intense.
 
Hydroxyzine Therapy and Pregnancy
Animal studies have found that fetal abnormalities occur at doses ten times higher than given to humans. It is not recommended that hydroxyzine be used if pregnant or nursing.

Other Antihistamines:
Some patients have reported a decrease in IC symptoms using other oral antihistamines, or medications with antihistamine properties, such as Claritin and Benadryl, or the newer leukotriene inhibitors such as Singulair. Hydroxyzine is contraindicated for use in epileptic patients.

Resources and References

  • Sant GR, Propert KJ, Hanno PM, Burks D, Culkin D, Diokno AC, Hardy C, Landis JR, Mayer R, Madigan R, Messing EM, Peters K, Theoharides TC, Warren J, Wein AJ, Steers W, Kusek JW, Nyberg LM; Interstitial Cystitis Clinical Trials Group. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol. 2003 Sep;170(3):816-7.
  • Theoharides, TC, and Sant, G, Hydroxyzine Therapy for interstitial Cystitis. Urology: Interstitial Cystitis Supplement to May 1997, Alan J. Wein, MD & Philip M Hanno, MD, Editors, pp. 108-110.
  • Theoharides, TC, Hydroxyzine in the Treatment of Interstitial Cystitis, Urologic Clinics of North America: Interstitial Cystitis, Philip M. Hanno, MD, Editor, February, 1994, pp. 113-119.

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Beyond the Abstract – Results of Endovesical Hyaluronic Acid/Chondroitin Sulfate in the Treatment of Interstitial Cystitis/Painful Bladder Syndrome

June 30, 2008 · Filed under Interstitial Cystitis

Tuesday, 24 June 2008
BERKELEY, CA (UroToday.com) – Hyaluronic acid (HA) is a natural proteoglycan that is hypothesized to replenish a defective glycosaminoglycan layer in interstitial cystitis/painful bladder syndrome (IC/PBS) (1) patients upon intravesical application. Initially, Morales (2) treated 25 patients and reported a 56% (week four) and 71% (week seven) response rate. Beyond week 24 effectiveness decreased but there was no significant toxicity. More recently, Nordling (3) reported a 3-year follow-up in a 3-month prospective, nonrandomized study evaluating the effect of intravesical hyaluronic acid on interstitial cystitis symptoms.

We based on the assumption that a more viscous compound than existent HA formulation, such as the one used, would be more effective in helping to restore a defective glycosaminoglycan layer. Besides, a solution consisting in a combination of HA and chondroitin sulphate, which had already been used as a single agent in IC/PBS patients (4), could produce additional benefits in patients than the use of its single components. Hyaluronic acid, also called sodium hyaluronate, was obtained in vials containing 40 ml of a clear, sterile, nonpyrogenic preparation of a high molecular weight fraction of sodium hyaluronate 1.6 % p/v associated with chondroitin sulfate 2.0 % p/v. Twenty-seven women 20 to 65 years old (mean 46.68, SD 13.63), with symptoms characteristic of Interstitial Cystitis/Painful Bladder Syndrome according to the criteria established by the National Institute of Health Consensus Conference (5) entered the trial, being recruited in two Centers.

After bladder catheterization with a sterile Nelaton catheter 10 or 12 Ch, the bladder was emptied, and the patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then be-weekly for 6 months, if there was initial response; a single dose of oral antibiotic was administered before catheterization. The solution was maintained for 1 hour before voiding. The primary endpoint of our trial was to evaluate the efficacy of a therapeutic regimen consisting in weekly intravesical instillations of sodium hyaluronate 1.6 p/v with chondroitin sulfate 2.0 % 1.6 p/v, for a period of 12 weeks, in female patients with a diagnosis of IC/PBS. To this aim, assessment of urgency and pain by means of VAS (10 cm), reduction of number of voiding by means of voiding diary, and O’Leary-Sant IC Symptom and Problem Index (6), and PUF questionnaire (7) were used.

Outcomes were evaluated at baseline and 3 and 6 months after initiation of therapy.

Results were evaluated by comparing pre and post-treatment values of the following tests: 3-days voiding diary, O’Leary-Sant Symptom score, PUF questionnaire; VAS for urgency and pain.

The baseline values were compared to 12-week assessment and 6 months assessment. The statistical analysis was performed using the T-test for independent variables. We considered statistically significant p< 0.05.

Results

A total of 23 female patients completed the study. More than 91% of patients reported having symptoms for more than 1 year.

Mean follow-up was 5 months, range 3 to 8 months. No patient had intolerance and/or side effects related to treatment.

There were 69% who presented with moderate/severe pain and 69% with moderate/severe urgency, defined as a score of 5 or greater on the 0 to 10 VAS scale. Most patients were on concomitant oral therapies to relieve their bothersome symptoms.

The data from the analysis of the questionnaires at baseline and after 12 weeks treatment are reported in Table 1 and 2. Both Interstitial Cystitis Symptom and Problem Index and Pelvic Pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement after 12 weeks of treatment.

The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks’ treatment period, with a significant reduction and increase, respectively (Fig. 1-2); mean voiding volume increased significantly, from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14).

The analysis of the VAS showed the improvement reported in Table 2.

Two patients had to stop weekly intravesical treatment due to urinary tract infections observed after catheterization, and two additional patients had to stop maintenance be-weekly home self-administration of the product after completing 12 weeks intravesical treatment, due to bacterial urinary tract infections.

Conclusion

In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitin sulphate appears to be a safe and efficacious method of treatment in IC/PBS. In responsive patients, the effect appeared to persist during maintenance treatment and follow-up visits, consisting in an improvement of both urgency-frequency related symptoms and bladder/pelvic pain. No significant side effects were recorded, and concomitant oral therapies could be continued.

In order to confirm these initial encouraging results, further controlled, randomized studies are necessary with a greater number of patients and a longer follow-up.

 

  

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Gabapentin Shown Effective for Fibromyalgia Pain

June 30, 2008 · Filed under Fibromyalgia Pain

New research supported by the National Institutes of Health?s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) shows that the anticonvulsant medication gabapentin, which is used for certain types of seizures, can be an effective treatment for the pain and other symptoms associated with the common, often hard-to-treat chronic pain disorder, fibromyalgia.

In the NIAMS-sponsored, randomized, double-blind clinical trial of 150 women (90 percent) and men with the condition, Lesley M. Arnold, M.D., director of the Women’s Health Research Program at the University of Cincinnati College of Medicine, and her colleagues found that those taking gabapentin at dosages of 1,200 to 2,400 mg daily for 12 weeks displayed significantly less pain than those taking placebo. Patients taking gabapentin also reported significantly better sleep and less fatigue. For the majority of participants, the drug was well tolerated. The most common side effects included dizziness and sedation, which were mild to moderate in severity in most cases.

NIAMS Director Stephen I. Katz. M.D., Ph.D., remarked that “While gabapentin does not have Food and Drug Administration approval for fibromyalgia1, I believe this study offers additional insight to physicians considering the drug for their fibromyalgia patients. Fibromyalgia is a debilitating condition for which current treatments are only modestly effective, so a study such as this is potentially good news for people with this common, painful condition.”

Fibromyalgia is a chronic disorder characterized by chronic, widespread muscle pain and tenderness, and is frequently accompanied by fatigue, insomnia, depression, and anxiety. It affects three million to six million Americans, mostly women, and can be disabling.

The precise cause of fibromyalgia in not known, but research suggests it is related to a problem with the central nervous system’s processing of pain. As with some other chronic pain conditions, people with fibromyalgia often develop a heightened response to stimuli, experiencing pain that would not cause problems in other people. Yet, unlike many other pain syndromes, there is no physical evidence of inflammation or central nervous system damage.

Although gabapentin has little, if any, effect on acute pain, it has shown a robust effect on pain caused by a heightened response to stimuli related to inflammation or nerve injury in animal models of chronic pain syndromes. Researchers have suspected that it might have the same effect in people with fibromyalgia. The new research, published in the April 2007 edition of Arthritis & Rheumatism, indicates the suspicions were correct.

Although the researchers cannot say with certainty how gabapentin helps reduce pain, Dr. Arnold says one possible explanation involves the binding of gabapentin to a specific subunit of voltage-gated calcium channels on neurons. “This binding reduces calcium flow into the nerve cell, which reduces the release of some signaling molecules involved in pain processing,” she says.

How gabapentin improves sleep and other symptoms is less clear, and there are probably different mechanisms involved in fibromyalgia symptoms. “Gabapentin improved sleep, which is an added benefit to patients with fibromyalgia who often report unrefreshing or disrupted sleep,” Dr. Arnold says. What is important is that people with fibromyalgia now have a potential new treatment option for a condition with few effective treatments. “Studies like this give clinicians evidence-based information to guide their treatment of patients,” says Dr. Arnold.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Arnold, LM et al . Gabapentin in the treatment of fibromyalgia; a randomized, double-blind, placebo-controlled multicenter trial. Arthritis Rheum . 2007; 56: 1336-1344.

1The FDA approved Lyrica (pregabalin) for treating fibromyalgia on June 21, 2007. (http://www.fda.gov/bbs/topics/news/2007/new01656.html;
http://www.fda.gov/consumer/updates/fibromyalgia062107

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