Promising New Treatment For Heart Failure

An anti-depressant drug developed over 40-years ago has been found to dull, even reverse muscle enlargement and weakened pumping function connected to heart failure, in animal experiments carried out by a team of researchers from Johns Hopkins.

Publishing their report in the journal Circulation Research, the heart experts describe how the no longer in use anti-depressant clorgyline, blocked enzyme monoamine oxidase-A (MAO-A) from breaking-down a key neurohormone in a dozen key laboratory experiments on rodents. The enzyme norepinephrine is responsible for controlling the the pace of blood pumping and in response to stress, it makes the heart pump harder and faster.

These findings are the first evidence showing how elevated MAO-A activity that bio-chemically drives heart failure can be stalled by drug therapy.

Insomnia, agitation, high blood pressure after ingesting foods containing the amino acid tyramine, a protein that stimulates a surge of stored stimulatory hormones, specifically, norepinephrine are some of the notable side effects from clorgyline.

Patients taking clorgyline and whose chemical binding to MAO-A is irreversible, should avoid tyramine-rich foods, such as, chocolate, red wine, certain beans, aged cheeses and meat.

An estimated 5.7-million American men and women suffer from chronic heart failure, which killed an estimated 290,000 people in 2005.

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New antidepressant class

Agomelatine (Valdoxan®) has been launched in the UK for the treatment of major depressive episodes in adults.

This new drug is a melatonin receptor agonist a serotonin-2c antagonist. The initial dose is 25mg daily taken at night and this dose may be doubled after two weeks if there is no symptom improvement.

The drug is not recommended in people under 18 years of age and those with active liver disease. Caution is required in people aged over 65 years and those who consume large quantities of alcohol. Liver function should be monitored at 12 and 24 weeks and treatment stopped if serum transaminases exceed three times the upper limit of normal.

Common side effects include gastrointestinal disturbances (nausea, diarrhoea, constipation and abdominal pain), headache, dizziness, insomnia, somnolence and liver function changes.

Agomelatine is available in 25mg tablets in packs of 28 at a cost to the NHS of £38.53. A month of treatment will therefore cost £38.53 to £77.06 depending on the daily dose.

Action: Clinicians should be aware of this new drug. It’s place in therapy is currently unclear and it may be prudent to limit use to specialists and continue to follow existing guidelines.

Source : www.prescriber.org.uk

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Do SRRI Drugs Interfere with Romance and Love?

By : Victoria Anisman-Reiner

SSRI drugs have known sexual side effects. Researchers believe they harm not only your sex life but the possibility of finding and sustaining love, romance, and marriage.

It's well-known that SSRI drugs can destroy sexual interest and lower libido. What many people taking antidepressants don't realize is that these effects can last long after a person stops using an SSRI, and the impact can be more than just sexual dysfunction and low libido: the long-term effects from these drugs may hinder the ability to reach an emotional connection with another person and to have a lasting relationship.

Selective Serotonin Reuptake Inhibitors and Sexual Dysfunction

Selective Serotonin Reuptake Inhibitors or "SSRI"s are a class of drug that is often prescribed for bipolar disorder, depression, manic or psychotic behavior, and even unexplained sadness or anxiety. These drugs work by altering the way nerve synapses uptake brain chemicals, specifically serotonin.

As a result, SSRIs are known to produce a slew of undesirable side effects, one of which is sexual dysfunction. SSRIs can lessen arousal and cause loss of libido, delayed orgasm, dulled sensitivity, and in many people a loss of interest in sex altogether.

Initial drug tests suggested that sexual dysfunction would be a side effect for roughly 10% of patients who use SSRIs. In fact, research indicates that loss of libido and some form of sexual side effects are prevalent in 60-70% of people taking SSRI drugs.

The Connection Between Lust, Attraction and Attachment

But that's just sex, right? It's possible to feel romance and even to have a fulfilling relationship without physical arousal, isn't it? Maybe so, and maybe not.

According to Rutgers university anthropologist, author, and sex expert Helen Fisher, the neural circuits that process lust, sexual interest, or arousal are the same ones that handle romantic attraction to another person and the attachment of falling in love.

Three brain systems operate simultaneously to feel lust, attraction and attachment – and changing the chemical way one of these systems operates with SSRI drugs can alter the others as well. "When you cripple a person's sexual desire and arousal," says Fisher, "you're also jeopardizing their ability to fall in love and to stay in love."

MRI scans indicate that the neural pathways that are used in romantic bonding and attachment can't function when serotonin levels are high – as they must be when SSRI drugs being used.

These pathways – and the development of romantic attachment – seem to require dopamine, a neurotransmitter whose levels are lowered by SSRIs.

How SSRIs Can Damage Relationships

SSRI drugs are known to cause something called "emotional blunting" – the sense of being distanced from emotions or of having them numbed to the point where they can't be felt clearly. Between this effect and the sexual side effects, SSRIs can have a serious impact on anyone hoping to begin or continue a long term relationship - and the effects can last long after discontinuing use of the drug.

"Post-SSRI sexual dysfunction" is the proper name for SSRI side effects that continue after drug use has ended. It's considered a sub-type of "SSRI discontinuation syndrome" – the violent physical and emotional effects of withdrawal. The sexual dysfunction part of SSRI withdrawal has been known to last months, years, or indefinitely.

Many SSRI users report distancing from their emotions, a loss of motivation, and less interest in reaching out to other people or in renewing friendships. Some even say they went on antidepressants and immediately lost the spark that connected them with a long-term love or the person they've been married to for years. These side effects are damaging not only to a person's sex life and reproductive health, but potentially to the ability to have a healthy, fulfilling relationship.

Source : depressiongrief.suite101.com

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Why Antidepressants Don't Live Up to the Hype

In the '90s, Americans grew fond of the idea that you can fix depression simply by taking a pill - most famously fluoxetine (better known as Prozac), though fluoxetine is just one of at least seven selective serotonin reuptake inhibitors (SSRIs) that have been prescribed to treat hundreds of millions of people around the world.

But in the past few years, researchers have challenged the effectiveness of Prozac and other SSRIs in several studies. For instance, a review published in the Journal of Affective Disorders in February attributed 68% of the benefit from antidepressants to the placebo effect. Likewise, a paper published in PLoS Medicine a year earlier suggested that widely used SSRIs, including Prozac, Effexor and Paxil, offer no clinically significant benefit over placebos for patients with moderate or severe depression. Meanwhile, pharmaceutical companies maintain that their research shows that SSRIs are powerful weapons against depression. (Here's a helpful blog post that summarizes the debate.)

Now a major new study suggests that both critics and proponents might be right about SSRIs: the drugs can work, but they appear to work best for only a subset of depressed patients - those with a limited range of psychological problems. People whose depression is compounded with, say, substance abuse or a personality disorder may not get much help from SSRIs - which is unfortunate for the 45% to 60% of patients in the U.S. who have been diagnosed with a common mental disorder like depression and also meet the criteria for at least one other disorder, like substance abuse. (Multiple diagnoses are known in medical parlance as comorbidities.)

The new study, published online in April by the American Journal of Psychiatry, was conducted using data from a large, government-funded trial called Sequenced Treatment Alternatives to Relieve Depression, which usually goes by the moniker STAR*D. The STAR*D project, which collected data from 2001 to 2004 at 41 U.S. psychiatric facilities, was one of the most ambitious efforts ever to understand how best to treat people with major depression. STAR*D participants comprise a powerful research sample because they are highly representative of all depressed Americans. Very few depressed people were excluded from STAR*D; only women who were pregnant, those with seizure disorders and a few others with acute conditions were kept out. All other psychiatric and medical comorbidities were allowed.

The authors of the new paper, a team of 11 researchers led by University of Pittsburgh professor of epidemiology Stephen Wisniewski, were curious how the STAR*D group would compare with a typical group of patients selected for a run-of-the-mill drug-company trial for a new antidepressant - the very trials on which the Food and Drug Administration bases its decisions regarding new drug approval. Drawing on their own experiences in helping to conduct such trials, which have far more stringent inclusion criteria than the STAR*D group, Wisniewski and his team divided the STAR*D patients into two groups - an "efficacy" sample of patients who would normally be included in a typical Phase III clinical trial for a new antidepressant and a "nonefficacy" sample of patients who would normally be rejected.

Depressed STAR*D patients who were classified for inclusion had no more than one general medical condition (like, say, heart disease) and no more than one additional primary psychiatric disorder besides depression. All patients with multiple comorbidities - along with anyone whose depression had lasted more than two years - were excluded. Once the authors crunched all the numbers, they found that only 22% of STAR*D patients met entry criteria for a conventional antidepressant trial.

All the STAR*D patients were taking citalopram, an SSRI marketed in North America as Celexa. Not surprisingly, those who met standard inclusion criteria for a clinical trial had significantly better outcomes on the drug. In the efficacy group, 52% responded to Celexa vs. 40% of the nonefficacy group. Patients in the latter group also took longer to respond and had to be readmitted to psychiatric settings more often. "Thus," the authors conclude, "current efficacy trials suggest a more optimistic outcome than is likely in practice, and the duration of adequate treatment suggested by data from efficacy trials may be too short."

To bolster their findings, the authors cite a smaller 2002 study that arrived at similar results: in that paper, published in the American Journal of Psychiatry, Dr. Mark Zimmerman of Brown University and his colleagues found that of 315 patients with major depressive disorder who sought care, only 29, or 9.2%, met typical criteria for an efficacy trial. Similarly, psychologist Ronald Kessler of Harvard co-authored a 2003 paper in the Journal of the American Medical Association that concluded that most "real world" patients with major depression would be excluded from clinical trials because of comorbidities.

Such findings help explain why antidepressants haven't quite lived up to their promise. But the University of Pittsburgh's Wisniewski, the lead author of the new study, cautions against interpreting the results as an indictment against greedy drug companies eager to exclude difficult patients in order to show better results. "If the population in a [clinical] trial were more representative, that would come at a cost," he says. Researchers expect a certain number of bad reactions during clinical trials; some of these reactions can cause serious medical problems. If patients enter a trial with multiple complications - if they are, say, not only depressed, but also cocaine-addicted, hypertensive and diabetic - you dramatically increase the chances of adverse side effects. "That's why trials to determine efficacy are done on a relatively homogeneous population," Wisniewski says.

That's understandable, but the new study does shed light on the limitations of antidepressants. Conducting clinical trials with representative samples would undoubtedly be more complex - and expensive - since patients with multiple risk factors would have to be monitored more carefully. But for a future generation of antidepressants to be truly effective for most patients, more-inclusive trials may be the best answer.

By : John Cloud

View this article on Time.com

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