New mechanisms of action found for drugs used to treat anxiety disorders

In the course of his or her life, every seventh German will develop an anxiety disorder that will require treatment. Standard anti-anxiety medications (anxiolytics) are based on the benzodiazepine class of drugs. These calm the patient and quickly diminish feelings of anxiety.

However, undesirable side effects like tiredness, drug intolerance and withdrawal problems make the long-term use of these drugs problematic. Scientists working under Rainer Rupprecht, Fellow of the Max Planck Institute of Psychiatry in Munich, succeeded in proving, for the first time, that new anxiolytics can be developed using an innovative mechanism based on neurosteroids derived from the hormone progesterone. This kind of drug displayed significantly fewer side effects, both in the animal tests and in a clinical trial.

A patient may be suffering from an anxiety disorder if he or she experiences feelings of anxiety that exceed the normal level and there is no identifiable cause of these feelings. Those affected by such disorders usually suffer considerably, both in their private and professional lives. In addition to psychotherapy and anti-depressives, which take a long time to take effect, benzodiazepines can usually alleviate the fear quickly and in the short term. However, these drugs can have considerable side effects if taken over longer periods, including, for example, the development of tolerance, dependence and withdrawal symptoms.

As part of their quest for new mechanisms of action for anti-depressives and anxiolytics, Florian Holsboer and Rainer Rupprecht at the Max Planck Institute of Psychiatry in Munich have been researching for years how neurosteroids influence the neuronal communication in the brain.

They examined the effect of a new class of substances in co-operation with the Department of Psychiatry of the Ludwig-Maximilians-Universität Munich and the Novartis pharmaceutical concern in Basel. The substance in question, XBD173, had a positive influence on the synthesis of the body’s neurosteroids and, as the scientists were able to prove with the help of mouse brain tissue, triggered the attenuation of neuronal communication as a result. XBD173 also displayed an anxiolytic effect on the behavioural level in the animal model without observing any sedating effects that arise, for example, with benzodiazepines. "I am absolutely delighted that the hypothesis we developed years ago, that anxiolytic effects can be attained by influencing the body’s neurosteroids, has been scientifically confirmed today," says Florian Holsboer in response to this latest finding.

In order to test the effect of XBD173 in humans for the first time, the doctors designed a clinical trial, in which 70 healthy volunteer subjects were tested. The subjects were injected with the neuropeptide fragment CCK-4, which triggered a short anxiety and panic attack lasting two to five minutes. When XBD173 was also administered to the subjects, the panic attack could not be triggered in this way. The benzodiazepine Alprazolam also curbed feelings of anxiety. However, in contrast to XBD173, the participants in the trial reported undesired fatigue on taking the drug and withdrawal symptoms on its discontinuation.

Thus, through the stimulation of neurosteroid synthesis using the translocator protein 18, the researchers discovered a new mechanism for the treatment of anxiety disorders that displays a better side-effect profile than benzodiazepine. In addition, the conditions were defined under which such studies can be carried out on healthy subjects. "The successful implementation of an experimentally inducible anxiety model in healthy subjects will facilitate the development of innovative anxiolytics in the future, as the testing of active ingredients in their early phase of development does not necessarily have to be carried out on patients," says Rainer Rupprecht.

He is, however, aware that insights gained on healthy subjects cannot necessarily be transferred to patients on a 1:1 basis. "They do not replace the necessary acceptance tests on patient groups."

Source : insciences.org

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German research points way to better anxiety drug

German scientists believe they may have found a better anxiety drug that can counteract panic attacks without the side effects caused by existing treatments like Valium.

Anxiety drugs such as Valium work well but produce side-effects that include drowsiness, forgetfulness and clumsiness and, when taken over time, can induce dependency.

The new compound, XBD173, appears to avoid these problems by targeting a different biological "don't panic" button, making it a good potential candidate for use as a safe and fast-acting anxiety pill.

Researchers published details of their experimental drug in the journal Science on Thursday, including encouraging results from an initial Phase I clinical study, which was sponsored by Swiss drugmaker Novartis.

A company spokesman said XBD173 was no longer in clinical development at Novartis but had been given to co-development partner Dainippon Sumitomo Pharma.

"What is needed right now is a rapid-acting anxiolytic (anxiety drug) that is effective but lacks the side effects of benzodiazepines," lead researcher Rainer Rupprecht of Munich's Ludwig Maximilian University said in a telephone interview.

"This shows that there is a possibility."

Roche's drug Valium, known generically as diazepam, is the best known of the benzodiazepine class of drugs, which have dominated the anxiety treatment market since the 1960s.

Antidepressants called selective serotonin reuptake inhibitors (SSRIs), such as Eli Lilly's Prozac, which is sold generically as fluoxetine, are also given for anxiety disorders but are of no use in acute episodes since they take several weeks to have an effect.

By contrast XBD173 worked within one hour of being given to rats in laboratory tests and also reduced panic in a week-long clinical study involving 70 healthy male volunteers given the new drug, an older benzodiazepine or a placebo.

The German team tested effectiveness by injecting subjects with a chemical called CCK-4 that is known to trigger a short-lived anxiety attack, which raises both heart rate and blood pressure.

They found that XBD173 produced a fast anti-anxiety response without any withdrawal symptoms after use.

The new compound works by promoting the synthesis of neurosteroids that modulate the effects of a brain chemical called GABA. Benzodiazepines also affect GABA, but in a different way.

Drug companies have been trying for some time to develop next-generation benzodiazepines by tweaking their chemical make-up to deliver a more selective effect that avoids unwanted side effects -- but it has proved an uphill struggle.

In 2003 Merck & Co abandoned one such drug, known as GABA Alpha 2/Alpha 3, after disappointing mid-stage clinical trials.

Source : www.reuters.com

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Using Herbal Supplements To Treat Anxiety Disorder

There is a marked shift today from allopathic medicine to alternative medication especially herbal medicine. If you are among those who would prefer natural cures, there are plenty to choose from that would help you control and reverse anxiety symptoms. Herbal medication works on the system overall, unlike allopathic treatment, which only aims at correcting the diseases causing chemical imbalance in the body. The result is that though the cure is a little slower comparatively, the side effects are less pronounced.

Unfortunately, the FDA does not approve many of the herbal supplements though many are excellent products. This is one reason why some people hesitate to use herbal medication, though they are not comfortable with the traditional medicines prescribed for this condition. You would be heartened to know that following the extraordinary increase in the demand for herbal medication special organizations came into existence, which work on the same lines as FDA but limit themselves only to classify herbal products and supplements. Whenever you are tempted to buy anything related to herbs, it would be a good thing if you run a scan on the product through these agencies.

One other way to choose the best herbal products is to follow the popularity charts of the leading brands. Most of these companies offer excellent products yet do not go for the certification of any of the above organization simply because this does not cover all the aspects of the product. For example, the certification would look into the potency of the medicines, percentage of the herbs face to face to the claims on the labels, and they would look into the hygiene aspects of manufacturing and packaging. However, none of the above really offers any guarantee or enlightenment on whether the product really works as per the claims made by the manufacturing company. Therefore, the major brands, which already enjoy the confidence of the masses and have a proven track, do not find it necessary to obtain the certification, which presently comes costly.

Many herbs work miracles with anxiety. I am bringing to your knowledge in the following few lines only a few of the most common ones. I am intentionally not providing dosages or methods of use, because I feel that anyone who wishes to use any type of medication should do so with the express advice and close monitoring of his or her medical practitioner. In case of herbal medicines, you would require to see a herbologist or a certified aurvedic practitioner. In most cases, you would have the choice of having your medicine specifically made for you, which is often a good option. However, if this does not appeal to you, you could always use the supplements and products available in the market.

It is important to note here that many herbal products use a combination of two or more of the herbs described below to boost the effect on the treatment of anxiety and depression. Attempting to have your own concoction at home, armed only with information from the Net can backfire terribly. For customized medicine, which is highly recommended, you need to take the assistance of qualified herbalists or ayurvedic doctors. Do not, under any circumstances, go for the trial and error method using your own self as a guinea pig. You might get worse before getting better, and you would definitely not profit from such an experience.

by : Ian Spencer
Source : www.articlecity.com

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The Side Effects Of Anxiety Medication

There are side effects. There is a downside involved in the treatment and cure of anxiety. However, complete cure is often a good possibility and suffering the side effects for a brief period well worth the trouble in the end. Normally doctors are very carefully about both the prescription of anti-anxiety medicines and the possibility of the surfacing of side effects. This is why most doctors would never prescribe any anti-depression or anxiety drugs over the phone as they feel that without a face-to-face evaluation it is impossible to judge correctly, how much and what is needed for best results.

The side effects are few if you are following the doctor’s prescription to the letter, which you should do when you are being treated for anxiety. Here a few that you should watch out for and inform your doctor if experienced at any time during your treatment:

1. A feeling of restlessness
2. Unexplained fatigue
3. Dizziness
4. Lethargy
5. Decrease in libido

The tricyclic anti-depressants for example, have serious side effects but are extremely effective in short-circuiting panic attack symptoms, which at the patient needs most at the time of treatment. Doctors prefer this medication to the ‘safer’ ones because of its ability to bring the system to normal much faster. Once things are under control, the less reactive drugs would be prescribed.

Each case of anxiety disorder differs from one another due to the circumstances that caused and triggered it. Based on the personal interaction the doctor would have with you, your medical history and the symptoms you are experiencing your medical practitioner would work out a customized line treatment that would best benefit you. This is why it is not wise to advise your friends about what drugs they should use for anxiety disorders based on your prescription, nor should you take their advice to treat yours based on their prescriptions. If and when you do so, you would be likely to get into more trouble than you started with.

The treatment does not end with the initial prescription and medication advice. You need to visit your doctor periodically who would monitor your progress through watching your external symptoms as well as through various tests - especially blood tests - so he would know how you are reacting to the medicines. Some people get rid of their anxiety in a couple of weeks; some in a couple of months or years while there would be yet another bracket of people who would require medication for the rest of their lives.

It is important that you follow the doctor’s advice to the letter and cooperate with him or her fully on very aspect of the treatment. It is often very helpful to adopt alternative means of relaxation and de-stressing while on medication such as yoga, meditation, mild exercising, and new diet and so on. Ensure however, that your doctor is aware of every little change you bring about in your life because every little detail counts while you are fighting anxiety off.

One small mistake and you would have to start from the beginning, often from worse condition that you initially were. The correct weaning of drugs you were prescribed for anxiety treatment is as important as the method of taking them in the initial phases. If you hurry this process along you would find that the withdrawal symptoms are often as bad if not worse than the anxiety symptoms themselves. To cap it, you would have to counter such symptoms with more drugs, which would add to the length of the treatment and your problems.

Keep in mind that though anxiety does not have any cure, you can totally have it under control. Modern medicine is fully equipped to control and reverse it. However, in order to do so you need to (i) get medical help, (ii) follow the instructions carefully, and (iii) be patient because the ‘cure’ would not happen overnight.

by : Ian Spencer
Source : www.articlecity.com

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