Hydroxyzine Article - Dr. Theoharides

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Re-sending a very good article written by Dr. Theoharides about Hydroxyzine and Mast Cells.... If anyone has IBS, Hydroxyzine has been used to help it, too. Hugs, Chelle Elliott wrote: ICA Update Dr. T.C. Theoharides, and internist, is the Professor of Pharmacology and Experimental Therapeutics, Biochemisty and Psychiatry, as well as Director of Graduate Pharmacology at the Tufts

School of Medicine in Boston. He and his colleagues at Tufts are currently conducting studies on the relationship of mast cells to IC and the effectiveness of the drug hydroxyzine in reducing pain and frequency in IC patients.The ICA Update asked Dr. Theoharides to discuss his research on hydroxyzine. Dr. Theoharides, can you tell us what hydroxyzine is? Hydroxyzine is a relatively mild anti-anxiety drug and antihistamine that also appears to decrease frequency and bladder pain significantly in many IC patients. Hydroxyzine comes in two forms: hydroxyzine pamoate (Vistaril) and hydroxyzine hydrochloride (Atarax). Both types of this drug are available as generic compounds and are approved by the FDA for a variety of indications. How did you discover that hydroxyzine might be effective in reducing pain and frequency in

IC? My interest in hydroxyzine grew out of our work on mast cells which occur in many tissues, including the brain and the bladder. When mast cells are triggered to secrete their contents, a process called degranulation, they release about 30 chemicals, some of which are prominent culprits in allergic and inflammatory reactions. In relation to our work on bladder mast cells, I screened a number of compounds that we had been testing for their effect on brain mast cells, which are activated in large numbers during migraine headaches. Of the drugs we looked at, hydroxyzine was one of the most effective in reducing the pain associated with migraines. We observed that a higher number of both bladder and brain mast cells would be triggered by acetylcholine or substance P, two potent neurochemicals that are involved in the pain transmission. In light of the information, it is not surprising that about 30% of IC patients also

suffer from migraines. We also found that both brain and bladder mast cell secretion produced in response to these chemicals are stimulated by estrogens. This may expalin why IC symptoms in women tend to worsen after ovulation or shortly before menstruation begins when estrogen levels are at their highest. (NOTE: My worst IC symptoms are when my estrogen levels are at their lowest "during" ovulation and right when I start. In addition, I'm always worse during the Luteal or second half of my cycle, but I've had progesterone dominance during that time. I personally think progesterone is harder on the bladder than estrogen. Estrogen may lead to more mast cells production, but it has very positive effects on uro/genital tissues. Also, Progesterone is dominant during the second half of the cycle, especially right before we start, so it might be the Progesterone causing trouble with those mast cells, just my

..02. - E.) Patients with allergies and even with irritable bowel syndrome have found that hydroxyzine improves both of these conditions as well as IC symptoms. What are the benefits of hydroxyzine therapy? There appear to be three specific benefits which occur in the following sequence: decrease nocturia, which enhances the ability to sleep at night, decreased daytime frequency, and decreased pain. How soon do these benefits occur? Some people begin to see benefits within a few weeks, while others take several months to experience substantial improvement. In our experience, patients rated their pain and frequency on a scale of one to ten, with one being the best. After three to four months, about 75% of the study respondents

rated their symptoms at about 4. After seven months, many who continued the regimen rated their pain and frequency as a 2. Do all patients repsond to hydroxyzine therapy? Unfortunately, no. Those who do not respond tend to be long time sufferers whose bladders are very scarred. Patients with allergies and even irritable bowel syndrome have found that hydroxyzine improves both of these conditions, as well as IC symptoms. What doses of hydroxyzine are being used? Most people in the study take an average of 50mg to 75mg a day. Those who take only 50mg take it all at night, while those taking 75mg usually take 50mg at night and 25mg during the day. This decreases the sedative effect in the daytime. After being on the drug for about one year, some people are able to cut

back to one-half dose without an increase in symptoms. What are the side effects? The only consistent side effects patients have reported are feeling sedated or tired in the morning. I would say that four to five days is about average. Dry mouth is another common side effect. Some people try to alleviate this symptom by drinking a lot of fluid but this worsens the frequency. We recommend rinsing the mouth out with water frequently to reduce dryness. Animal studies have found fetal abnormalities occur at doses ten times higher than given to humans; therefore, it is best to avoid use during pregnancy and nursing. (NOTE: With my ob/gyn's permission, I used Vistaril 50mg's a day during the second and third tri-mesters with my second son (2002-2003). He is perfectly healthy. I even called Motherisk (http://www.motherisk.org) in Canada they informed me that their studies on hydroxyzine had not shown any birth defects.) However, the American College of Allergy and Clinical Immunology recently rated hydroxyzine safer than Benadryl - a common antihistamine found in "cold" medicine - during pregnancy. At very high doses (over 250mg a day), patients may experience slight temors in their hands, but this promptly disappears upon reducing the dose. What happens if you stop taking hydroxyzine? When people stop taking hydroxyzine, the symtpoms usually return within a few days. People often forget how bad their symptoms were before taking the drug, and initially report them as worse, when in fact they may not be so bad. As with many drugs, you have to keep taking it to maintain the

effects. Symptoms disappear upon resuming hydroxyzine. Who should not take hydroxyzine? Hydroxyzine is contraindicated for people with epilepsy - it might increase the frequency or severity of seizures - and should be used with caution by people who are diagnosed with depression. It may make the depression a little worse. If you are diagnosed as having depression, and decide to try hydroxyzine, your condition should be carefully monitored by your therapist or physician. How is the study being conducted? Dr. G.R. Sant, the Associate Chairman of Urology at the New England Medical Center, and I have seen patients here in Boston. However, most of the patients are being prescribed hydroxyzine by their own physicians, and are then returning questionnaires to me rating their symptoms on a scale of one to ten. Even though

these rating are subjective, they can be quantified by standard statistical methods.