Zoloft Depression

Getting a Better Handle on Antidepressant Action

August 26, 2007

Researchers have identified a new mechanism by which tricyclic antidepressants (TCAs) inhibit neurotransmitter transporters—a discovery that may improve the design of new antidepressants that are more effective than the TCAs currently on the market. TCAs, which have been prescribed for decades, have been largely supplanted by selective serotonin reuptake inhibitors because of their lack of specificity.

Howard Hughes Medical Institute investigator Eric Gouaux at Oregon Health & Science University (OHSU) and colleagues Satinder K. Singh and Atsuko Yamashita published their findings August 8, 2007, in an advance online publication in the journal Nature. Singh, the paper’s first author, was an HHMI predoctoral fellow and is now a postdoctoral fellow at OHSU. Yamashita, formerly with the Gouaux group at Columbia University, is and now a team leader at the RIKEN SPring-8 Center in Japan.

“There is no question that knowledge of the mechanistic principles and details of this drug-binding site will be important in developing a new class of molecules that act very specifically on only a selected type of transporter.”
Eric Gouaux

The researchers began their studies with the goal of understanding how TCAs interact with their clinical target, sodium-coupled neurotransmitter transporters. These transporters mop up neurotransmitters from the synapse, the junction between neurons. Neurotransmitters are molecules that neurons use to communicate with neighboring neurons. TCAs work by inhibiting the reuptake of neurotransmitters by neurons.

Disorders such as depression, epilepsy, autism, or obsessive-compulsive disorder can result from impaired function of sodium-coupled neurotransmitter transporters. Thus, these molecules are the target of a variety of drugs, including TCAs.

It has been a great challenge, however, to understand precisely how these molecules function and interact with drugs. The problem, Gouaux said, is that the transporters found in humans are not amenable to study.

“It’s tough to get cells to make much transporter, and once you isolate the protein, it just falls apart, like a soufflé that falls coming out of the oven,” he said. So the researchers focused on a sturdier transporter in bacteria that functions similarly. That molecule, called LeuT, is used by the bacterium Aquifex aeolicus, which thrives in superheated deep-sea vents. LeuT’s job is to transport the amino acid leucine across the bacterial membrane.

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Singh explored how the TCA clomipramine, which she had found to be a potent inhibitor of LeuT, attached to the bacterial transporter. Singh used x-ray crystallography to develop a detailed structure of clomipramine attached to LeuT. She also analyzed how two other TCAs, desipramine and imipramine, attached to LeuT. In x-ray crystallography studies, researchers bombard protein crystals with x-rays and then deduce the structure of the protein by analyzing the diffraction pattern produced by the x-rays.

One plausible way for a drug to interfere with a transporter’s function is by physically blocking the part of the molecule that binds to the molecule to be transported. Singh’s steady-state kinetic data and crystallographic studies revealed, however, that clomipramine and the other TCAs do not attach to the same site on the transporter as leucine. Rather, they plug into a cleft in a different part of the transporter and lock it into a conformation that traps leucine, preventing it both from passing through and being released. This cleft is on the region of the transporter that juts outside the cell.

Similar findings were reported in a research article published in the August 9, 2007, issue of Science, by Da-Neng Wang, Maarten Reith and colleagues at New York University. They found that the TCA desipramine binds LeuT in the same cleft. The two groups diverge in their conclusions about the relevance of the TCA site in LeuT to the antidepressant site in the human neurotransmitter transporters, however. Wang, Reith, and colleagues argue that it is identical, whereas Singh and her colleagues are more cautious, suggesting that the TCA site is different and probably located ‘deeper’ into the human transporter, close to or overlapping with the substrate site.

Nevertheless, the concept that a molecule binding to an allosteric site may inhibit a transporter by stabilizing an occluded or locked state is one that had not been described previously. Singh, Gouaux, and Atsuko hypothesized that the TCA molecules slowed the release of leucine from the transporter. Sure enough, in her experiments, Singh found that the transporter released leucine about 700 times slower when clomipramine was attached. “When I followed the reaction, the off-rate was so slow with clomipramine that it took one day. But with no inhibitor, the leucine fell off in less than ten minutes,” she said.

“This study defines a new principle for inhibition of this class of sodium-coupled transporters,” said Gouaux, “and that is the stabilization of this so-called occluded state. The dogma in this field has been that molecules had to be designed to competitively inhibit the transport process by acting as a surrogate yet non-transported substrate. But nobody had any evidence to suggest that stabilization of this occluded state was the mechanism.”

Gouaux said that discovery of the new mechanism may spur development of improved inhibitors. “There is no question that knowledge of the mechanistic principles and details of this drug-binding site will be important in developing a new class of molecules that act very specifically on only a selected type of transporter,” he said. “You can certainly come up with molecules that potently inhibit in this manner, and they don’t need to look like the substrate. They can look very different and still plug this extracellular vestibule.

In future studies, Gouaux said he and colleagues will seek to isolate and crystallize the delicate human transporter for structural studies to establish if the basic same inhibitory mechanism is at work.

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Depression often misdiagnosed and incorrectly treated

August 23, 2007

I often hear this sort of comment, and it makes me shudder, as it represents a very serious problem which prevents many people from getting proper treatment for their depression. Let’s run through the many problems included in such a statement.

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First, there’s a common misunderstanding of the nature of depression itself, and the person in this situation may not be significantly depressed at all. Depression is one of the commonest human afflictions. It is serious, it hurts and it has a significant death rate (mainly from suicide); a death rate rather higher than that of many other diseases which are treated more seriously by everyone.

In some ways, it’s unfortunate that the disorder has come to have such a simple name: “depression”, rather than an impressive technical term - or it might get more respect. Depression is a word, like anxiety, which is in common use for a wide range of states, including depression, but also many milder, more transient situations - such as the blues, feeling down in the dumps, sad, disgruntled, disappointed, displeased, unhappy, cheerless, gloomy, downcast and so on.

Major depression
The presence of so many terms, in most languages, for such negative moods, shows how common they are. But the sort of serious depression that needs serious treatment, goes beyond these (while often including all of them) and involves a range of biochemical changes in one’s brain function. Indeed, some specialists talk of a “biochemical depression” in order to make the distinction. All these other, lesser, mood states deserve respect and concern, but they are significantly different in degree and in significance.
What makes a major depression a significant illness rather than these unpleasant but briefer and more shallow moods, is the depth, extent and duration of the change in mood, and the extent of its effects on normal functioning. Depression certainly features a severe degree of depressed mood, though some people seriously affected by it experience the other symptoms more severely and may not even recognise their state as depression. The criteria which specialists and doctors use to diagnose depression look for this miserable mood to be present for most of the day, nearly every day. All normal people have variations in their mood, and it dips down for some of the time. But that isn’t depression.

Closely related to this is another criterion we look for, and one that is often even more reliable in indicating the presence of a real depression: a markedly diminished interest in whatever usually interests you, a loss of pleasure in what usually pleases you (technically called anhedonia ).

The state should represent a real change from someone’s previous state and not arising from an obvious immediate cause such as the death of a loved one (though depression can arise in the course of a bereavement); and it causes functional impairment: you are significantly less able to function as well as you usually do.

There are several other features common in depression, which people often do not recognise as related, such as fatigue and loss of energy, difficulty in concentrating and making decisions, and feelings of being unworthy, and guilty, far in excess of anything that might be a reasonable response to events. In a number of areas of functioning, the symptoms may swing in either direction - one may have insomnia, or sleep excessively, still not feeling refreshed by it. There can be increase in appetite and weight gain, or loss of appetite and weight loss; and one may become agitated and restless, or retarded and slowed down. Commonly, also, there are recurrent thoughts of death and futility, and thoughts of suicide.

This, then, is Depression with a Capital D, and the situation in which antidepressant drugs can be very useful, indeed life-saving. While Depression can vary in severity, unless it is severe enough to meet the set of criteria specialists use to make the diagnosis, it is not severe enough to benefit from antidepressant therapy at all. Too often, when the doctor says you have a “mild depression” he is hedging his bets. He is not really convinced whether the problem is severe enough to need serious and proper treatment. Far too often, he then talks of giving a minor or mild dose of an antidepressant drug.

Drugs must be used properly
Now comes the second problem. One must either use the antidepressant drugs properly and in a sufficient dose to have a significant impact on correcting the biochemical abnormalities than have arisen in the depression; or not use it at all. For each such drug, there is a minimum dose below which it will not produce any benefits. Lower doses may well give nasty side effects and even some risks, without any risk of benefiting the patient. It is simply an expensive and unpleasant way of taking needless risks. Many research studies and surveys have found that a great many patients in general practice are receiving far too little of the drug to be able to benefit from it. Some of the people who say they have been treated with antidepressants, but without feeling better, fall into this category.

Pharmacy - Buy Pharmacy at discount prices including free shipping.Discount Pharmacy provides confortable and easy way to order discount pharmacy online.Doctors also often fail to wait long enough to see if a drug is working. Effective antidepressants may help to improve some aspects of your depression even earlier, but generally need a good two weeks to make a substantial difference to your condition. Too often, as a specialist, I see someone referred to me who has been given almost every antidepressant drug known to medical science, but who has had none of them in a sufficient dose or for a sufficient period. They might in fact respond excellently to any of those drugs, but have usually so thoroughly lost faith and confidence in that possibility, as to make their treatment needlessly difficult.

I also, too often, see patients whose depression has been treated with drugs which have no useful antidepressant effect, like the Valium family of tranquillisers. Such chemicals can even worsen a depression and increase one’s impulsivity, which can be dangerous - just as alcohol, self-administered by many people in an effort to find a way to feel better, can have the same unfortunate effects.

Side-effects
Some drugs, especially the older antidepressants, have more side-effects, and one may very well start on a rather low dose, and gradually increase it to the effective level. This is fine, so long as the process is supervised by a doctor who knows what she is doing, and so long as the effective blood levels of the drug are reached. Newer antidepressants have less noticeable side effects, and can even be started at a potentially effective dose from the start. One may need to tolerate some degree of side effects, and accept them as a sign that the drug is getting to the right places and also doing what you want it to be doing.
A medication that is totally free of side effects would probably be just as free of effects and benefits, as well. Even a placebo a dummy medication, consisting of starch, sugar pills or an injection of sterile water) usually also has side effects. In drug trials using a placebo in comparison with an active drug, some patients complain bitterly of the side effects of the placebo, even stopping the non-existent drug, calling it intolerable.

Depression often not noticed
Some doctors, who were never very well trained in psychiatry when in medical school (the medical schools in South Africa rather ignored this important aspect of medicine until the last decade or so) don’t take depression seriously enough. They may not recognise it when they see it. Depression often acts as an amplifier of any other symptoms one has, making them feel worse and harder to tolerate. Thus, depressed patients often go to see their doctor with other complaints at the top of their list (and doctors are often in such a hurry that they never let you tell them more than the top one or two complaints on your list).
We find a very high incidence of treatable and curable depression among patients at general medical or surgical outpatients departments or in medical or surgical hospital wards. Depression which amplifies pain may worsen someone’s complaints about a relatively unimportant problem and lead to them being wheeled in for surgery, which will not solve their major problem.

Depression can be sneaky, either coming on so gradually that you don’t really notice how severely it is affecting you before you are fully in its grip; or developing relatively rapidly, so that the tiredness, indecisiveness and hopelessness it causes within you, lead you to be inactive, give up and not take action to see a suitable professional who can help you get better.

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Antidepressant Effectiveness May Depend on Genes

August 19, 2007

Researchers say they’ve found a key gene variation influencing whether or not people respond to the antidepressant Celexa.Having both this variant and a previously discovered gene means a person is 23 percent more likely to respond to the drug than people without either variation. Celexa (citalopram) is one of a widely used class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which also include Paxil, Prozac and Zoloft.

While these medications do appear to reduce depression for many who use them, their benefits vary widely among patients. The reasons behind that variance have remained unclear, experts say.

But the new finding “suggests that we’re going down the right path, although we’re not there yet,” said Dr. Gonzalo Laje, co-author of the study, which is published in the August issue of the American Journal of Psychiatry. “We are better able to see how genetic variations help determine how a person may or may not respond to a certain medication. This is an advancement toward personalized medicine.”

Laje is associate clinical investigator at the U.S. National Institute of Mental Health, which conducted the study.

However, the increased likelihood of response for people carrying the gene was relatively modest, indicating that only the sum of many genes — most yet to be discovered — will give scientists the whole story, experts said.

“There’s no one marker that’s going to tell you whether you respond or not. It’s a lot of markers, each one having a small effect,” said Dr. Julio Licinio, chairman of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine. “This is another building block, but it’s not the whole story. In the future, as we put all these markers together, we may be able to develop a genetic panel to tell us whether a person is likely to respond to an SSRI or not.”

Different people respond differently to different medications, and that’s true for a wide variety of drugs, not just antidepressants. But with depression, especially, some patients respond happily to the first medication they try, while others have to go through a frustrating trial-and-error process before finding the right solution for their illness, if they find a solution at all.

Internet Pharmacy - Buy Pharmacy at reasanoble prices.Internet Pharmacy provides confortable and easy way to order pharmacy via internet.The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest effectiveness study ever done on depression, examined the benefits of antidepressants in “real world” settings.

SSRIs are considered among the most effective treatments available for depression. However, doctors haven’t had good evidence on the best course of action to take if or when a patient fails to respond to a particular SSRI.

The STAR*D trial was designed to answer that question.

An earlier analysis of STAR*D data had found that people with a variation in the HTR2A gene were more likely to respond to Celexa.

For this analysis, the researchers looked at DNA from more than 1,800 patients who had also participated in the STAR*D trial, comparing genes in people who had responded to Celexa and those who hadn’t.

This time, it appeared that people with a variation in the GRIK4 gene had a higher likelihood of responding to the drug. The researchers also confirmed that the HTR2A variation also made people more likely to respond.

HTR2A produces a protein that acts as a receptor for serotonin, a neurotransmitter long implicated in depression.

GRIK4 makes a protein that acts as a receptor for the glutamate neurotransmitter system, which is beginning to be implicated in depression.

“This gives us very relevant information to where we should be looking. We are understanding that glutamate receptors are important for antidepressant outcomes,” Laje said.

Another paper in the same issue of the journal found that about 25 percent of people who enrolled in STAR*D actually dropped out during the first three months, with one third of those not coming back after their first visit. Those most likely to discontinue treatment included younger individuals, those with less education, blacks, Hispanics and people with drug or alcohol abuse problems or anxiety

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Indications for Antidepressant use in patients with chronic pain disorders

August 18, 2007

Chronic pain is common; an estimated 20% of primary care visits focus on this problem. Nearly 25% of patients with diabetes develop neuropathic pain. Traumas, strokes, HIV/AIDS, and alcohol abuse are other common medical problems that can produce a chronic pain disorder. The aging American population guarantees the continued prominence of chronic pain disorders. Managing chronic pain is one of the most challenging problems that both physicians and patients face. Extensive diagnostic assessment may shed little light on the etiology of the disorder, leaving both the physician and the patient in an uncomfortable position. The physician’s goal is pain control, which may not produce total relief from symptoms. Multiple interventions may be required to manage the patient’s expectations when intractable pain relentlessly intrudes on his or her daily life. An empathetic health care provider can offer education, emotional support, medical referrals as needed, and, perhaps most importantly, a wide range of pharmacologic interventions to palliate the discomfort.

An effective approach for the management of chronic pain begins with a thorough assessment and concludes with a targeted biopsychosocial treatment plan. The assessment identifies the functional disability associated with the pain and provides sufficient justification for educational interventions. In addition, the social impact of the debilitating pain disorder might lead the physician to suggest counseling opportunities for the immediate family. Naturally, the patient’s principal objective is maximum pain relief. Among the pharmacologic options available and in addition to standard analgesic remedies, antidepressants can be an important ally in the physician’s quest for safe pain management.
USE OF ANTIDEPRESSANTS IN THE MANAGEMENT OF CHRONIC PAIN
Pain and depression are closely intertwined, strongly hinting at a shared neurophysiology. As a consequence, one prevailing pharmacologic strategy identifies a central role for serotonin and norepinephrine reuptake inhibitors (SNRIs).1 Other justifications, even without a common biologic rationale, strongly support the use of antidepressants in the management of chronic pain. For example, chronic pain characteristically causes sleep problems, anxiety, and depression, all of which may improve with antidepressant treatment.2 Providing an effective, nonhabituating sleep medication that also improves mood may significantly enhance the patient’s quality of life.

Clinical evidence suggests that antidepressants exert their beneficial analgesic effect directly, apart from the physiologic mood improvement. When examining the use of antidepressants among persons who have fibromyalgia or diabetic peripheral neuropathic pain, a recent study concluded that more than 75% of the improvement in painful symptoms was due to the direct analgesic role of the medication.3 Patients may initially not appreciate the recommendation of taking an antidepressant for a pain disorder, but a moment’s education stressing the unique analgesic action of antidepressants should satisfy that concern.

Clinical investigators report effective pain relief across the spectrum of presently available antidepressants. Not surprisingly, the bulk of published studies focus on the tricyclic antidepressants (TCAs). Their efficacy in chronic pain management is well established.4,5 The efficacy of antidepressants, specifically TCAs, in the management of chronic pain is recognized in clinical practice guidelines;6,7 typical guidelines recommend the initial use of TCAs for neuropathic pain. Studies have revealed that patients with specific pain disorders, such as diabetic neuropathy and postherpetic neuralgia, seem more likely to benefit from TCAs than patients who experience the chronic discomfort associated with neck or back pain.8

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Although TCAs have a long-established record of safety, efficacy, and tolerability in the role of augmenting chronic pain management, prudent prescribing requires awareness of the major adverse effects of TCAs, which predominantly cluster around cholinergic, histamine, and adrenergic receptor activity. As a consequence, dry mouth, sedation, constipation, urinary hesitancy, and orthostatic hypotension are among the potential adverse effects. Additionally, TCAs should be used with considerable caution in the presence of certain medical conditions, such as glaucoma and benign prostatic hypertrophy. They should also be avoided in the presence of second- or third-degree heart block or a prolonged QT interval.9

Chronic pain management with TCAs can usually be achieved at much lower doses than those typically required for an antidepressant effect. Clinicians can expect results at one half of the antidepressant doses. For example, a starting dose of desipramine would be 10 mg, with 10-15 mg adjustments made weekly until improvement is noted or a dose of 50 mg is reached. Limited improvement at 50 mg might justify a tricyclic blood level test, dose increase, or referral to a specialty pain management clinic.

Other classes of antidepressants have also been studied in the management of chronic pain conditions. The secondary amines, such as desipramine or nortriptyline, also provide effective relief from chronic pain. A particular advantage of the secondary amines is better tolerability and safety, which is the result of less intense anticholinergic adverse effects and less sedation. As a consequence, these medications may be the better and safer choice for chronic pain management in elderly patients.10 Clinical evidence also supports the efficacy of the newer selective serotonin reuptake inhibitors (SSRIs) in relieving chronic pain, although the data may be, comparatively, less convincing.11,12 This may, in part, be because of the broader array of neurotransmitters that are involved in the maintenance of chronic pain, instead of simply serotonin. TCAs and secondary amines inhibit the reuptake of both serotonin and norepinephrine.

The notion that other neurotransmitters are involved in mediating pain is further supported by the emerging efficacy of SNRIs in relieving chronic pain. Venlafaxine is an SNRI used in the treatment of chronic disorders such as fibromyalgia and postmastectomy pain syndrome.13 Duloxetine is an SNRI with clinical treatment indications for both major depression and diabetic peripheral neuropathic pain. This newer antidepressant is a more potent inhibitor of serotonin and norepinephrine reuptake than are other similar medications. As with TCAs, duloxetine’s analgesic effects appear independent from its antidepressant actions. Duloxetine is the first antidepressant approved by the US Food and Drug Administration (FDA) for the management of the pain associated with diabetic peripheral neuropathy. Numerous studies positively cite duloxetine’s effectiveness in managing pain among elderly patients, its role in managing fibromyalgia, and its relief of the pain associated with diabetic peripheral neuropathy.14-16

CONCLUSION
The basis for all treatment of chronic pain conditions begins with a thorough pain assessment. The assessment should include the use of structured instruments to determine both the severity of pain and the associated functional impairments. A psychological assessment is an important routine step in the development of a chronic pain care plan. The assessment must also include a determination of the patient’s safety in terms of potential suicide risk. In conjunction with or in lieu of analgesic options, antidepressant therapy or augmentation may be suggested for patients with lingering stress, depression, insomnia, and lack of remission with standard analgesic remedies. Given the breadth of available clinical research and comparatively lower cost for TCAs, this class of antidepressants remains the preferred initial option, but the newer antidepressants (eg, venlafaxine, duloxetine) should be considered an alternative if TCAs prove ineffective.

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GlaxoSmithKline’s Deadly Cover-Up

August 10, 2007

A striking young woman with a talent for painting, Sharise Gatchell was — like many teenagers — painfully self-conscious. At 14, she moved with her family from South Africa to England where at first she found it hard to make friends. By the age of 16 she was acutely embarrassed that her periods hadn’t started and felt she was sweating excessively. Just the sort of thing to make adolescence even more painful than usual. Her mother, Stephanie, took her to see a consultant physician at the local hospital. Stephanie Gatchell recalls:

“During that consultation she became a bit emotional because she was explaining to him about the problems she had and how it affected her social life. Then she started crying and I was amazed. He asked her, ‘Sharise, do you sometimes feel like ending it all?’, and I couldn’t believe it when she said ‘Yes I do.’ And then he started talking about paroxetine and suggesting that she try it.”

“Off-label” Prescriptions

Paroxetine — better known as Paxil in the U.S. — is an antidepressant. It is licensed only for adults, but doctors are allowed to prescribe any medicine if they think it will help their patient, a practice called “off-label” prescribing. Sharise was not the only teenager getting paroxetine off-label. Around 7,000 children a year were on the drug in the UK; and many more in the U.S.

Within days of starting on paroxetine, Stephanie noticed a dramatic change in her daughter: she became more confident. But with the confidence came aggression and worse:

“One day in the kitchen her sleeve pulled up slightly and I noticed that there were cut marks on her left arm. I couldn’t believe my eyes. She was obviously self-harming while she was on the drug, something she’s never ever done before.”

Stephanie persuaded her daughter to stop taking paroxetine. But in 2003 Sharise went back on it without telling her mother. When her parents returned from a weekend break, Stephanie immediately realized something was terribly wrong:

“I went upstairs before my husband came in, and the moment I got to the landing at the top and I turned round and looked, she was hanging from the loft hatch. I tried to revive her, but before I even started I realized I was too late.”

Next to her daughter’s suicide note lay a packet of paroxetine. Stephanie instinctively blamed the drug and now blames herself for letting her daughter take it. But she couldn’t have known what the drug’s manufacturer had known for years.

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UK-based GlaxoSmithKline (GSK), the second largest drug company in the world, which recorded 2006 sales of over $45 billion, had begun a series of clinical trials in the mid-1990s to test whether paroxetine would work in depressed children. Paroxetine had already been hailed as a wonder drug in adults as a treatment for everything from depression and stress to anxiety and even shyness. By the new millennium 100 million paroxetine prescriptions had been written worldwide, bringing in $2 billion a year for GSK and placing the antidepressant a close second to Prozac in popularity.

With the adult market sewn up, the company sought new ways to make money from the drug, or “life cycle management,” as the approach is known in the pharmaceutical industry. The U.S. Food and Drug Administration wanted to boost the number of medicines tested for children and had introduced an incentive that would give companies a six-month extension on their patent just for carrying out pediatric trials. For paroxetine alone that would be worth $1 billion. And if GSK could be the first company to prove its antidepressant was safe and effective for children, the rewards would be even higher, as paroxetine could become the market leader.

Hundreds of children were recruited from around the world to take part in three clinical trials. One group was given the drug, the other a placebo. They were randomized controlled trials (RCT) where neither the children nor their doctors knew whether they were taking the active drug or the placebo until the end of the study. This is widely accepted as the best way of working out whether a drug causes a particular effect: the gold standard in terms of evidence.

But the outcome of these the trials was not what GSK had been hoping for. Paroxetine proved no better than placebo. In the biggest trial, Study 329, which was conducted across several sites in the U.S., 11 of the 93 children who took paroxetine developed serious side-effects; seven had to be hospitalized. Significantly more had self-harmed or attempted suicide on the drug than on placebo.

The BBC (British Broadcasting Corporation) obtained confidential case reports from Study 329 which detail what happened to them:

“[13 days after starting paroxetine] the patient became very angry. He punched pictures, broke glass and sustained lacerations that required six sutures… he expressed hopelessness and possible suicide thoughts.”

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Suicide risk in adults lowered by antidepressants

August 7, 2007

Adults with depression who are treated with a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs) have a lower rate of suicide attempts, the results of a new study indicate.In October 2004, the U.S. Food and Drug Administration (FDA) ordered drug labeling to warn of a possible link between antidepressant drug treatment and suicidal thoughts, or “ideation,” and behavior in children and adolescents, the researchers note in the American Journal of Psychiatry. In May 2007, the warning was extended to include young adults.

Dr. Robert D. Gibbons, of the University of Illinois at Chicago, and colleagues examined the association between antidepressant treatment and suicide attempts in adult patients treated in the Veterans Administration health care system.

Data were analyzed for 226,866 veterans without a history of depression as of 2000-2002, but had been diagnosed with depression by 2003-2004 and were followed for at least 6 months. The team compared the suicide attempt rates before and after the patients began treatment with SSRIs or tricyclic antidepressants.

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Overall, 114,475 subjects were treated with one drug within one class of antidepressants; 72 percent received an SSRI, 24 percent received a non-SSRI and 4 percent were given a tricyclic antidepressant. Another 52,959 patients received a combination of antidepressant drugs and 59,432 were not treated.Suicide attempt rates were lower after treatment than before treatment, the team reports. A comparison of suicide attempts before and after treatment with a single SSRI also revealed lower risk for patients in all age groups. This relationship was statistically significant in all but the 18 to 25 age group, “possibly because of the smaller number of patients in that age group in the VA population and the small number of events.”

The rate of suicide attempts was also lower among patients treated with antidepressants compared with those who were not. Specifically, the overall suicide attempt rate after initiation of SSRI treatment (alone or in combination with another antidepressant) was 364 per 100,000, while the rate for all other patients with depression was 1,057 per 100,000.

Suicide attempt rates among patients who received any antidepressant, compared with untreated patients was lower for all age groups, Gibbons and colleagues found.

They conclude that SSRI treatment has a protective effect against suicide in all adult age groups — and the results of their study “do not support the hypothesis that SSRI treatment places patients at greater risk of suicide.”

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Antidepressant stigma

August 2, 2007

Many people suffer from depression, which may range from mild to debilitating. It may be the result of life circumstances, hormonal influences, or the individual’s body chemistry.

Some mild depression requires no treatment. It goes away on its own. Situational depression may lift when action is taken to change the circumstances contributing to the problem.

When depression is deeper, or more long lasting, that is when it can interfere with the quality of life. Some turn to drugs or alcohol. Others feel sad all the time and lose interest in the things they used to enjoy. Relationships can be affected.

In severe depression the individual may not even want to get out of bed, neglect personal self-care, or even become suicidal.

Discount Pharmacy - Buy Pharmacy at discount prices including free shipping.Discount Pharmacy provides confortable and easy way to order discount pharmacy online.There are common sense things that can be done to help alleviate depression. Getting exercise, eating healthy foods in normal amounts, getting a good night’s sleep and avoiding negative people all help.

Seeing a therapist is also advisable, and some individuals require anti-depressant medication. In some cases it is true that a combination of therapy and medication together work better than either one alone.

Unfortunately some are reluctant to consider medication because they feel there is a stigma attached to having to take medication.

I tell my clients it is no different than a diabetic having to take insulin. A depression with biochemical attributes is neither the person’s fault, nor is it a weakness.

If you are someone who requires this medication, do not be hard on yourself. If you are someone who has never been depressed, or required such medication, be supportive of those who require it. Do not make jokes about anti-depressants because there is a good chance someone in the room is taking them. (To obtain my Healing Depression CD, see below.)

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Change in behavior may be new meds

July 29, 2007

My 16-year-old daughter has been taking an antidepressant drug for depression for 10 months. She was doing better and enjoying life but in the past few weeks her sadness has set back in. She isolates herself and I hear her crying all the time. She’s irritable and refuses to participate in family activities. Her doctor wants to increase her drug dosage again. Do you think this will help?

K.T.,SACREMENTO, CALIF.

A: It’s hard to say; this might work for a short time. Generally speaking, however, the higher the dosage, the greater her risk for side effects such as insomnia, headache, dizziness, low appetite and confusion. I’m not a psychiatrist, but it’s clear that the doctor thinks your daughter is slipping backward, so he’s prescribing a higher dosage again. This may very well be the case, but I have to warn you that this change in your daughter’s behavior could be due to her medication, not a relapse into depression. I say that because antidepressants have been linked to suicidal thoughts (and yes, suicide) in children and teens, although it’s unusual. The U.S. Food and Drug Administration requires that antidepressant drugs carry a special ‘black box’ warning about the danger. Some of the signs and symptoms to watch for include worsening depression, anger and thoughts or talk of suicide.

I offer natural ways to ease depression, as well as safety tips if you take prescribed antidepressants in Chapter 5 of my book, ‘The 24-Hour Pharmacist.’ As a caring mom, you need to ask your daughter whether or not she’s experimenting with other drugs like alcohol or cocaine — another reason for emotional disorders. Combining these substances with antidepressants is extremely dangerous. Learn more about her lifestyle (could she be pregnant?) and also talk to her doctor(s). Finally, consider the following safe and natural remedies to take with her medication: essential fatty acids, magnesium chelate, B-complex, vitamin C, Panax ginseng and green tea.

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Q: I’ve been having hot flashes so I bought a cream containing ‘wild yam’ extract from a health food store to help balance my hormones, particularly progesterone. Will this do the trick?

T.E., LOS ANGELES, CALIF.

A: No, that would not be my pick. The theory that wild yam converts to progesterone in the body is not bullet-proof. It sounds good, especially when you hear someone explain the biochemical reasoning, but according to some leading hormone gurus, wild yam extract is not the same as pure progesterone itself. Diosgenin (found in wild yam) has some activity in the body, and under strict laboratory conditions, along with solvents, it can convert itself into some steroid hormones.

These lab solvents are not found in a woman’s body, however — see why I like USP pure progesterone better than wild yam extract? Because when you buy progesterone, you get progesterone. Period.

Suzy Cohen’s column is distributed by Tribune Media Services and is published Tuesdays in the TimesDaily. Visit her at dearpharmacist.com.

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Child Antidepressant Use Soaring in the UK

July 26, 2007

The number of prescriptions for child antidepressants written by GPs in the UK have risen to more than 631,000 in the last financial year, a huge difference to the 146,000 written in the mid-1990s.

Discount Pharmacy - Buy Pharmacy at discount prices including free shipping.Discount Pharmacy provides confortable and easy way to order discount pharmacy online.UK’s shadow children’s secretary, David Laws, said: I think it is a major concern that drugs seem to be prescribed so easily these days to children of school age.

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Wyeth’s Net Income Rises 13%

July 22, 2007

Wyeth’s second-quarter income rose 13% due to continued strong sales of Prevnar, its vaccine for pneumococcal diseases, and its arthritis drug Enbrel.

The Madison, N.J., pharmaceutical company, which also raised its 2007 earnings guidance, said net income rose to $1.2 billion, or 87 cents a share, from $1.06 billion, or 78 cents a share, a year earlier.

Results from the latest quarter included a charge of three cents a share from productivity initiatives, and the year-earlier quarter included charges of two cents a share. Excluding items, earnings rose to 90 cents from 80 cents a share.

Wyeth said revenue rose almost 10% to $5.65 billion from $5.16 billion a year earlier. On average, analysts polled by Thomson Financial expected earnings of 87 cents a share and revenue of $5.48 billion.

Sales of Effexor, Wyeth’s top-selling antidepressant drug, rose 6% to $997 million. Earlier this month, Wyeth filed a patent-infringement lawsuit against Mylan Laboratories Inc. to stop the company from selling a generic version of its blockbuster Effexor XR antidepressant. Effexor had $3.7 billion in sales in 2006 and is the best-selling antidepressant in the world. Wyeth claims the patents for Effexor XR — the extended-release version — expire in 2017.

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Last year, Wyeth settled a patent-infringement case with generic drug maker Teva Pharmaceutical Industries Ltd. regarding Effexor. Teva now sells generic versions of the immediate-release version of Effexor, which comprise a small portion of overall Effexor sales.

During the quarter, Prevnar sales jumped 22% to $633 million, and international sales of Enbrel climbed 37% to $508 million. Wyeth co-markets Enbrel — which treats rheumatoid arthritis and psoriasis — with Amgen Inc. Amgen handles sales in North America.

Wyeth’s divisions performed well: The consumer-health unit posted a revenue increase of 4% to $623 million, while animal-health sales increased 2% to $279 million. The pharmaceuticals division reported a sales jump of 11% to $4.75 billion.

Wyeth raised its 2007 earnings guidance to a range of $3.48 to $3.56 a share from $3.40 to $3.50 a share, excluding items. On average, analysts are expecting earnings of $3.49 a share.

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