RxPG News : Antidepressants

Antidepressants that are more efficient and faster

Tue, 05 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) In the PhD defended by the pharmacologist and biochemist Jorge Emilio Ortega Calvo at the University of the Basque Country, a new anti-depressant treatment strategy is proposed that is capable of improving on the current one with its drawbacks.

Depression is a chronic and recurrent illness that can affect at least 20% of the population at some period in their lifetime, according to a number of studies carried out. Moreover, according to the WHO, by 2020 emotional state disorders could be the foremost or second cause for sick leave from work in the developed countries. Current ant-depressive therapies, nevertheless, are far from optimum.

This was the theme of the PhD presented by the pharmacologist and biochemist from the Basque province of Gipuzkoa, Jorge Emilio Ortega Calvo, undertaken at the Faculty of Medicine and Odontology of the University of the Basque Country (UPV/EHU). Basically it was a study in which an analysis was undertaken of the action mechanisms of current antidepressant pharmacological drugs and new antidepressant treatment strategies put forward and that could be useful in the near future in order to address the failings in the current ones.

Antidepressant Augmentation Can Be Useful in Treatment Resistant Elderly Patients

Thu, 07 Jun 2007 15:59:37 PST

( from http://www.rxpgnews.com ) Adding a medication to a standard treatment regimen for major depressive disorder in the elderly improves chances of recovery in those who do not adequately respond to the first-course therapy or who relapse from it, finds a University of Pittsburgh School of Medicine study published in the June issue of the American Journal of Psychiatry, the official journal of the American Psychiatric Association. Up to 84 percent of the elderly who experience depression either fail to respond to first-course treatment or relapse during the first six to 12 weeks of treatment.

The study found that adding a second drug to the treatment of depressed participants over the age of 70 who either did not respond to initial treatment with the antidepressant paroxetine and interpersonal psychotherapy, or to those who responded to the initial treatment but quickly relapsed, caused the likelihood of recovery to rise from 40 percent to 60 percent. Recovery was slower in those who did not respond to the original treatment.

"Depression should not be considered a normal part of aging. The scientific evidence is growing that there are a number of effective treatment options available for people of all ages," said Mary Amanda Dew, Ph.D., professor of psychiatry, psychology and epidemiology at the University of Pittsburgh and lead author of the study.

The University of Pittsburgh researchers followed 105 adults aged 70 or older who had major depressive disorder and who did not respond to standardized treatment of paroxetine and interpersonal psychotherapy or who did respond but experienced an early recurrence of depressive symptoms. Participants were given one of three augmenting agents: sustained-release bupropion, nortriptyline or lithium. Researchers selected the additional agent that each participant received based on individual medical status and history. Thirty-six participants either declined new medicine or did not receive augmentation because of accompanying medical conditions.

Half of the patients who did not respond to the initial treatment responded to the augmentation therapy. It took a median 28 weeks for the participants to achieve recovery. Of the patients who relapsed after the initial therapy, 67 percent recovered after augmentation over a median recovery time of 24 weeks. Of the patients who responded to the first-course therapy of paroxetine and psychotherapy, 87 percent achieved recovery.

"While the recovery rates of those receiving augmentation are not as high as in those who responded to first-line therapy, the recovery rates are still high enough to suggest that augmentation should be tried when older adults' depression is not improving," said Dr. Dew.

Certain anti-depressants double fracture risk

Tue, 23 Jan 2007 14:21:16 PST

( from http://www.rxpgnews.com ) New York, Jan 23 - Daily use of certain anti-depressant drugs could double the risk of fractures in adults above 50 years of age because of their effect on bone physiology, says a new study.

Researchers at the Centre for Bone and Periodontal Research at McGill University in Montreal evaluated 5,008 adults who were aged 50 and above.

They studied them for over five years to see if they experienced 'fragility' fractures -- the type suffered from relatively minor traumas such as falling out of bed, reported the online edition of health Magazine WebMD.

A total of 137 participants reported daily use of Selective Serotonin Reuptake Inhibitors - - a class of anti-depressants.

Despite adjusting for factors known to increase fracture risk like falls, low bone density and physical inactivity, the adults on SSRI anti-depressants had twice the risk of fractures than those not on antidepressants.

'In the SSRI group, there were 18 X-ray confirmed fragility fractures out of 137 people or 13.5 percent,' said researcher David Goltzman.

'In the non-user group, there were 317 X-ray confirmed fragility fractures out of 4,871 people, or 6.5 percent,' he added.

'If you are over 50 and your doctor prescribes an SSRI, go have a bone density test first, especially if you have had a fracture from a minor trauma,' suggested Goltzman.

The findings of the study appeared in the Jan 22 issue of the journal 'Archives of Internal Medicine'. But the researchers added that people should not stop taking SSRIs if their doctor thinks that drugs can help them battle depression.

STAR*D Trial: Third antidepressant medication might help in treatment-resistant depression

Mon, 10 Jul 2006 21:00:37 PST

( from http://www.rxpgnews.com ) The next wave of results from the nation's largest real-world study of treatment-resistant depression shows that patients had a moderate chance of becoming symptom-free when they switched to a third antidepressant medication, following two previously unsuccessful medication attempts. These results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, funded by NIMH, were published in the American Journal of Psychiatry on July 1, 2006.

During Levels 1 and 2 of the STAR*D trial, which started with 2,876 participants, about half of all patients became symptom-free. Of the other half, about one in five became symptom-free when they went on to Level 3 and switched medications again.

"STAR*D continues to provide valuable real-world information about treating depression," said NIMH Director Thomas R. Insel, M.D. "Not only are the results enlightening, but they are telling us that more research is needed to help people with this debilitating illness, especially those who have tried several treatments and the treatments have failed."

As in Level 2, patients in Level 3 were given the choice of either switching medications or adding another medication to their existing medication; 234 patients chose to switch medications in Level 3. The results for those who chose to add to their existing medication will be available later in 2006.

The patients were randomly assigned to take either mirtazapine (Remeron), an "atypical" antidepressant, or nortriptyline (Aventyl or Pamelor), a tricyclic antidepressant, for up to 14 weeks. Both work differently in the brain than the selective serotonin reuptake inhibitors (SSRIs) and other medication used in Levels 1 and 2 of the STAR*D trial.

Overall, the two medications were about equally effective with 10 to 20 percent of patients becoming symptom-free. The type and severity of side effects were similar for both medications. In addition, neither medication resulted in a faster improvement rate than the other, suggesting that no clear advantage exists for either medication.

"Patients who do not respond to two consecutive antidepressant trials should not give up. Many of them will get better if they keep trying different treatment regimens or combinations, although the benefits from a third trial of an antidepressant alone appear to be rather modest," said lead author Maurizio Fava, MD, of the Massachusetts General Hospital in Boston.

SSRI anti-depressants may cause stillbirth

Mon, 10 Apr 2006 13:53:37 PST

( from http://www.rxpgnews.com ) Women who take a type of antidepressant medication during pregnancy face the risk of a stillborn baby, warns a study.

Canadian researchers at the University of Ottawa compared the health of babies born to 972 women taking SSRI (selective serotonin reuptake inhibitors) with that of babies born to mothers who did not use anti-depressants.

They found that women using the drugs were twice as likely to have a stillbirth. They were also almost twice as likely to have a low birth weight baby, reported the online edition of BBC News.

Babies born to women using SSRIs were also more likely to have seizures, the study published in the American Journal of Obstetrics and Gynaecology said.

SSRIs work by increasing levels of the mood chemical serotonin in the brain. Babies born to women using SSRIs were also more likely to have seizures, the researchers said.

"Left untreated, the physical and psychological effects of depression can lead to problems during pregnancy," said Charlotte Davies of Tommy's, the baby charity.

"Sufferers of depression are far more likely to smoke, as well as lose their appetites and in extreme cases are more likely to attempt suicide, which can all have devastating effects on mother and baby."

Whilst this study has found a correlation between SSRIs and pregnancy complications, it has in no way confirmed a clear causal effect between the two.

The researchers said women using these anti-depressants should be fully briefed about the potential risk by their physicians. Pregnant women could opt for other types of anti-depressant medication, they said.

Anti-depressant use associated with increased risk for heart patients

Mon, 06 Mar 2006 17:23:37 PST

( from http://www.rxpgnews.com ) In a surprising finding, patients with coronary artery disease who take commonly used antidepressant drugs may be at significantly higher risk of death, Duke University Medical Center researchers have found.

Even after controlling for such factors as age, degree of heart disease and severity of depression, the researchers found that heart patients taking antidepressant medications had a 55 percent higher risk of dying. Previously, Duke researchers reported that the presence of depression is an important risk factor for heart patients. This new finding of the risk from anti-depressants raises issues about the optimal way to treat depression in cardiac patients, the researchers said.

According to Duke team leader Lana Watkins, Ph.D., the researchers believe their findings add further support for the potential role oft non-pharmocological approaches to treating depression, such as exercise, in reducing the risk of death in depressed heart patients. She said that physicians caring for heart patients who are taking antidepressants should monitor patients closely.

Watkins added that the design of the study prevents definitive conclusions regarding the effects of antidepressant drugs. In the current observational study, patients were not randomized to receive an antidepressant or a placebo drug, therefore characteristics of the patients, such as more likelihood for their depression or their medical condition to worsen, may be responsible for the effects, she said.

Randomized placebo-controlled trials are needed to not only replicate the Duke findings, but to better understand whether antidepressant use is identifying patients likely to have more severe or worsening depression or worsening medical disease during the follow-up period, Watkins added.

"This finding that antidepressant use was an independent risk factor for mortality in patients with coronary artery disease was quite unexpected," said Watkins, who presented the results of the Duke study March 4, 2006, at the annual meeting of the American Psychosomatic Society in Denver. The research was supported by the National Heart, Lung, and Blood Institute.

"We were surprised since antidepressants, particularly the newer class of antidepressants known as selective serotonin reuptake inhibitors (SSRI), have been generally considered safe," Watkins said. "However, even after taking into account many patient variables, as well as the type of antidepressant, the risk still remained. So there is something important going on here that we don't fully understand."

During the past decade, cardiologists and physicians have gained a greater appreciation that depression should be considered as an important risk factor for patients with coronary artery disease, said the researchers. For this reason, they have increasingly prescribed antidepressants for these patients; however, this increase in use has not been accompanied by conclusive scientific data on the effects of antidepressants especially SSRIs on mortality.

For her study, Watkins prospectively analyzed the clinical data of 921 Duke University Hospital patients receiving a cardiac angiography procedure to determine the extent of blockage in their coronary arteries. Of the total number of patients, just under one in five (19.4 percent) were taking an antidepressant; with SSRIs being taken by 66 percent of those patients.

During their hospitalization, patients were given the Beck Depression Inventory (BDI), a commonly used depression screening test. In general, patients with a BDI score of 10 or higher are considered depressed. In the Duke study, those patients who were not taking antidepressants had an average BDI score of 7, while those on antidepressants had an average score of 11, a statistically significant difference.

The patients were followed over an average of three years, and during that time 21.4 percent of the patients who were taking antidepressants had died, compared to 12.5 percent for those not on antidepressants.

After adjusting for such factors as age, gender, heart pumping strength, smoking history, degree of other illnesses, heart procedures, BDI score and education, the researchers found that patients taking antidepressants had a 55 percent higher risk of dying. The difference between SSRI and non-SSRI use 61 percent vs. 49 percent was not statistically significant.

Watkins said the future studies are needed to uncover the reasons responsible for depression's negative effect on mortality. Also, she said, researchers do not fully understand the physiological effects of SSRIs on patients with coronary artery disease.

While physicians do not know why there appears to be a link between depression and increased risk of mortality, there are a number of theories, said Watkins. Depression has been linked to supression of the immune system, as well as alteration of the aggregation properties of blood platelets. It has also been linked to other such cardiovascular risk factors as insulin resistance, hypertension, obesity, increased cigarette smoking, alcohol abuse and physical inactivity, she noted.

SSRIs linked with increased risk of persistent pulmonary hypertension in newborns

Fri, 10 Feb 2006 15:51:37 PST

( from http://www.rxpgnews.com ) A University of California , San Diego (UCSD) School of Medicine collaborative study with Boston University s Slone Epidemiology Center found an increased risk of persistent pulmonary hypertension (PPHN) in newborns of mothers who used certain commonly prescribed antidepressants in late pregnancy. The results of the study will be published in the February 9 issue of the New England Journal of Medicine.

According to the study authors, PPHN is a serious condition that typically involves severe respiratory failure in a newborn infant and requires immediate treatment. The condition occurs in about one to two per thousand babies. The new study findings indicate that pregnant women who take one of the antidepressants known as selective serotonin reuptake inhibitors or SSRIs, such as Prozac ® , Paxil ® or Zoloft ® , in the second half of pregnancy have a small but significantly increased chance of delivering an infant who develops PPHN. The study found that exposure to antidepressants other than SSRIs did not pose a risk for PPHN. In addition, women who discontinued use of SSRIs in the first half of pregnancy did not have an increased risk of delivering a child with the condition.

These findings may be important for pregnant women and clinicians when making decisions about the most appropriate treatments for depression late in pregnancy.

Lead author on the study, Christina Chambers, Ph.D., M.P.H., of the Departments of Pediatrics and Family and Preventive Medicine at UCSD, worked with a team of investigators who identified at birth 377 infants with PPHN and 836 normal newborns from 97 delivery hospitals in four metropolitan centers in the U.S. and Canada between 1998 and 2003. The study was part of the ongoing Birth Defects Surveillance Program being conducted by the Slone Epidemiology Center with the collaboration of 17 San Diego County hospitals including UCSD Medical Center.

Within six months after birth, the researchers examined the records and carefully interviewed the mothers of children with PPHN and the mothers of the matched control infants selected from the same hospitals. The mothers in both groups were asked specifically about the use of any antidepressant medications during pregnancy, the names of products used, and the timing in gestation when the mother used the medication. Mothers were also queried about a wide variety of other maternal exposures, medical history, pregnancy history, and lifestyle factors.

Based on our findings, we estimate that six to twelve mothers per thousand who use an SSRI after 20 weeks gestation, are likely to deliver a child with PPHN, said Chambers. Put in practical terms, the risk is relatively low -- about 99 percent of women exposed to one of these medications during the latter half of pregnancy will deliver an infant unaffected by PPHN.

Our findings suggest that prenatal exposure to SSRIs might contribute to the pathological origin of this disorder, says Chambers. She adds that although the study cannot establish cause, several possible mechanisms suggesting an association between the use of the SSRIs and PPHN are plausible.

Although the researchers noted an increased risk of PPHN in infants whose mothers took SSRIs late in pregnancy, the research team points out that mothers may need to continue SSRI treatment during pregnancy in order to care for themselves appropriately. The findings of this study might be factored into decisions about continuing treatment with SSRIs into late pregnancy.

The research team consisted of Chambers, Sonia Hernandez-Diaz, M.D. Dr.P.H of Slone Epidemiology Center at Boston University School of Public Health, Linda J. Van Marter, M.D., Ph.D of Boston Childrens Hospital, Brigham and Womens Hospital, and Harvard Medical School, Martha M. Werler, Sc.D, and Allen A. Mitchell, M.D. of Slone Epidemiology Center, and Kenneth Lyons Jones, M.D. of the UCSD Department of Pediatrics.

Chambers is Program Director of the California Teratogen Information Service (CTIS). CTIS operates a statewide telephone service and a clinical research program from the Department of Pediatrics at UCSD with satellite offices at UCLA, Los Angeles Childrens Hospital and Stanford University. Founded in 1979, this program provides no-cost, confidential information regarding the fetal safety of medications, chemicals, or other agents when used in pregnancy. The CTIS Pregnancy Risk Information line provides information to over 8,000 callers per year including pregnant or pre-pregnant women and health care providers located throughout the state of California. The CTIS program also conducts pregnancy outcome research studies so that evidence-based information can be developed for women with similar questions in the future.

Antidepressants may affect human immune system

Sat, 21 Jan 2006 21:53:37 PST

( from http://www.rxpgnews.com ) Drugs that treat depression by manipulating the neurotransmitter serotonin in the brain may also affect the user's immune system in ways that are not yet understood, say scientists from Georgetown University Medical Center and a Canadian research institute.

That's because the investigators found, for the first time, that serotonin is passed between key cells in the immune system, and that the chemical is specifically used to activate an immune response. They do not know yet, however, whether these SSRI (selective serotonin reuptake inhibitors) drugs "including the brands Prozac, Zoloft, Paxil and others" could have either a beneficial or a damaging effect on human immunity.

"The wider health implication is that commonly used SSRI antidepressants, which target the uptake of serotonin into neurons, may also impact the uptake in immune cells," said Gerard Ahern, Ph.D., assistant professor of Pharmacology at Georgetown and lead researcher on the study.

He said that while it may be possible that SSRI drugs may restore a healthy immune function in people who are depressed and prone to infections, it is possible that they might also bolster immunity to the point that they trigger autoimmune disease. "At this point we just don't know how these drugs might affect immunity, so we really need to clarify the normal role of serotonin in immune cell functioning," Ahern said.

The surprising finding that serotonin is rapidly passed between immune cells in a manner similar to its transmission between brain neurons was revealed in mid-October, when the research team published the findings in the journal Blood. In December, the discovery was highlighted for the general scientific audience by the journal Nature Reviews Immunology, and now the research team is working to produce an animal model that may help describe the precise nature of this interaction.

"The novelty is that we reveal a potential communication, involving the transmitter serotonin, between immune cells that is normally only found between neurons," Ahern said.

In addition to Ahern, Peta Connell, Ph.D., from the Robarts Research Institute in Canada, was also a co-lead researcher on the study. Scientists from the Robarts Research Institute also contributed to the work.

In the brain, serotonin transmission between neurons is associated with feelings of pleasure, mood, and appetite, and the class of antidepressants known as SSRIs keeps serotonin active within the synaptic spaces between neurons, enhancing the chemical's positive effects. Unlike in the brain, which uses chemical messengers to communicate between nerve cells, the immune system is believed to "converse" through physical contact -- one type of immune cell touches another, setting off a response.

Specifically, "antigen presenting cells" display their antigens (bits of a foreign invader) to T-cells, and a resulting physical coupling between the antigens and the T-cells will prompt the T-cells to divide and expand in population, triggering an immune response designed to destroy the invader. This process may take hours.

What the Georgetown researchers found, however, is that dendritic cells -- the most powerful of the antigen-presenting cells and the ones that can find invaders that have never infected the body and "educate" the immune system to fight them -- also use serotonin to quickly excite a T-cell response. They discovered that these dendritic cells can rapidly secrete serotonin, which activates serotonin receptors on certain types of T-cells.

"In addition to the physical contact, it surprised us to find that these immune cells also have machinery to take up serotonin and to secrete it in an excitatory manner," Ahern said. "The point behind this transmission is not entirely clear, but it appears to be an additional way of stimulating a T cell response."

Drugs that block serotonin reuptake "likely change some of the parameters of T-cell activation, but we don't know yet if it enhances or inhibits the total immune response," Ahern said. "But it is something that should be explored because we really have no idea what SSRIs are doing to people's immune systems."

Suicide risk decrease after initiation of antidepressants

Sun, 01 Jan 2006 20:40:37 PST

( from http://www.rxpgnews.com ) The risk of serious suicide attempts or death by suicide generally decreases in the weeks after patients start taking antidepressant medication, according to a new study led by Group Health Cooperative researchers and published in the January issue of The American Journal of Psychiatry. The study also found that the risk of suicidal behavior after starting 10 newer antidepressant medications is less than the risk posed by older medications.

These findings challenge a 2004 advisory by the U.S. Food and Drug Administration (FDA), which warned that suicidal behavior may emerge after treatment with the newer antidepressant drugs has begun.

"Our findings show that, fortunately, suicide attempts and death by suicide are rare following the initiation of antidepressants," says Greg Simon, MD, MPH, a Group Health psychiatrist and the lead researcher on the study. "The period right after people start taking antidepressant medication is not a period of increased risk. In fact, risk after starting medication is lower than before."

This study is the first published analysis to compare the risk of suicide attempts before treatment to the risks following treatment. It is based on computerized medical and pharmacy records for more than 65,000 patients who filled prescriptions for antidepressants from 1992 to 2003. Deaths by suicide were determined from death certificates and suicide attempts were identified from hospital discharge data.

Group Health researchers found that the number of suicide attempts fell by 60 percent in adults during the month after antidepressant treatment began, and declined further in the following five months. Among the 65,103 patients taking antidepressants, there were 31 completed suicides in the six months following the antidepressant prescription. That rate was not higher in the one month after the prescription than in subsequent months. The study also found that newer antidepressants were associated with a faster decline in rates of suicidal behavior than older drugs.

Adolescents in the study had more suicide attempts than adults. The researchers found that the rate for the first six months of antidepressant treatment was 314 attempts per 100,000 in teens and 78 attempts per 100,000 in adults. As with adults, the rate was highest in the month before treatment and declined by about 60 percent after treatment began.

Given recent public concern over a possible link between suicide and antidepressants, Simon says he fears people may mistakenly believe that suicidal behavior is common after taking antidepressant medications. That misperception could lead to fewer people with depression being treated with medications proven to be effective in battling depression, he adds.

"There may be subgroups of people who become more agitated or suicidal after taking these drugs, and those people should seek help from a doctor or therapist right away if that happens," says Simon. "But our study showed that on average, the risk of suicide actually goes down after people start taking the antidepressant."

Simon agrees with the FDA's recommendations that doctors carefully monitor people taking antidepressants. "Keeping a close watch on patients after they begin taking these drugs is a good idea--although not because these medicines are especially risky or dangerous," he says. "Patients need to be monitored to ensure they're getting the right medication in the amount that can help them feel better."

'Promiscuous' area of brain could explain role of antidepressants

Thu, 07 Apr 2005 18:10:38 PST

( from http://www.rxpgnews.com ) A study at Baylor College of Medicine in Houston may lead to a better understanding of how antidepressants like Prozac work and how to make them more effective.

According to results published in today's issue of the journal Neuron, a study in mice proposes that dopamine and serotonin neurotransmitter systems in the brain occasionally get their signals crossed, causing delays in stabilizing mood.

"This study provides a new site for drug discovery in one of the biggest market for drugs those that treat symptoms of depression," said Dr. John Dani, professor of neuroscience at BCM and lead author of the study.

Dani's study, funded by the National Institutes of Health, offers an alternative explanation for the delayed effect of most antidepressants.

"Some scientists thought that you had to take an antidepressant for weeks because as serotonin is elevated, some of its receptors had to turn off and become desensitized rather than be stimulated," Dani said. "That didn't make a lot of sense to us since desensitization is usually a rapid mechanism."

Serotonin and dopamine neurotransmitter systems, which factor heavily in regulating mood, emotional balance, and psychosis, are released and reabsorbed in the striatum, an area of the brain which affects motivation and reward-based learning. Dani's findings indicate that these systems may be less selective and more "promiscuous" than previously believed.

"There has been a fundamental principal in neuroscience that a neuron releases one neurotransmitter," said Dani. "We have come to realize that neurotransmitters aren't the perfect 1-to-1signalers that we assumed they're a little promiscuous. That is, rather than transporting one neurotransmitter, these systems may transport other neurotransmitters as well."

A better understanding of how antidepressants work would come as welcome news to those who suffer from depressive disorders, a leading cause of disability worldwide. Over 14 million adults experience depression each year in the United States alone.

"Instead of taking serotonin up as they normally would into serotonin neurons, it is taken up into the terminals for dopamine so that now when your neurons fire to send a dopamine signal, they're actually also sending a little bit of a serotonin signal," Dani said. "This kind of interaction among neurotransmitter systems alters the timing of how these neurotransmitter systems act, and in that way, it certainly impacts how you process information."

Depression is commonly treated with selective serotonin reuptake inhibitors (SSRIs) like Prozac to elevate and prolong the presence of the neurotransmitter serotonin in the brain. By blocking the uptake of serotonin after its initial release, conventional antidepressants provide the brain more serotonin for a longer period of ti

Cordance QEEG can assess Susceptibility to Antidepressant Side Effects

Thu, 31 Mar 2005 16:09:38 PST

( from http://www.rxpgnews.com ) In a finding that opens new doors to determining susceptibility to antidepressant side effects, researchers at the UCLA Neuropsychiatric Institute report that changes in brain activity prior to treatment with antidepressants can flag patient vulnerability.

The study is the first to link brain function and medication side effects, and to show a relationship between brain function changes during brief placebo treatment and later side effects during treatment with medication.

The study's unique design compares brain function changes in healthy research subjects with no history of depression while taking an antidepressant vs. placebo, a pill with inactive ingredients. In addition, all participants took only placebo for one week prior to randomization to medication or placebo.

Using "cordance," a quantitative electroencephalography (QEEG) imaging technique developed at UCLA, the research team found changes in brain function in the prefrontal region during the one-week placebo lead-in were related to side effects in subjects who received an antidepressant.

"This finding shows the promise of new ways for assessing susceptibility to antidepressant side effects," said Aimee M. Hunter, lead author and research fellow at the UCLA Neuropsychiatric Institute.

"The ability to identify individuals who are at greatest risk of side effects would greatly improve the success rate of antidepressant treatment," Hunter said. "For example, physicians might select a medication with a lower side-effect profile, start medication at a lower dose or opt for psychotherapy alone when treating patients susceptible to antidepressant side effects."

Antidepressant side effects can be related to medication or to factors such as patient expectations derived from educational materials or consultations with a physician, but determining vulnerability or cause in a clinical setting is difficult.

To overcome this hurdle, the UCLA research team used healthy subjects so that brain function would not be affected by illness or changes in the illness. The team examined QEEG cordance during a placebo lead-in so brain function changes in the first phase of the trial could arise from only non-medication factors.

The study enrolled 32 healthy subjects who had never suffered from depression. All underwent a one-week, single-blind placebo lead-in before being randomized to four weeks of double-blind treatment with the antidepressant venlafaxine or placebo. Members of the research team met with subjects at seven time points over the course of the study -- at baseline, the end of the placebo lead-in, after randomization and weekly after randomization.

A research nurse obtained side effect reports during each visit, systematically asking subjects about specific complaints, including gastrointestinal upset, cardiovascular disturbance, sleep disturbance, anxiety and agitation. EEG readings were obtained at visits throughout the study. Changes in prefrontal brain function observed before start of medication signaled a greater number of adverse effects during antidepressant treatment.

Research shows St. John's Wart as effective as Paroxetine

Fri, 11 Feb 2005 19:42:38 PST

( from http://www.rxpgnews.com ) A specially manufactured extract from the herb St John's Wort is at least as effective in treating depression as a commonly prescribed anti-depressant, according to new research published on bmj.com today.

St John's Wort* and the anti-depressant drug Paroxetine** were used in a trial to treat patients with moderate or severe depression. The researchers asked 301 participants of both sexes from German mental health centres to take part in the trial. The two drugs were taken by the patients aged 18-70 over a six week period during 2000 -2003.

At the end of the trial half (61 out of 122) of those who took St John's Wort found their symptoms in decline, whilst only a third (43 out of 122) of those taking Paroxetine went into remission.

Participants also suffered more side-effects by taking Paroxetine with 269 adverse effects being reported over the treatment period. Those taking St John's Wort reported 172 adverse effects the most common in both cases being stomach disorders.

The authors support the use of St John's Wort as an alternative to treat depression and welcome more research in this area.

Multiple Medication Use Increase as a Function of Age and Antidepressant Use,studies show

Sun, 06 Feb 2005 11:56:38 PST

( from http://www.rxpgnews.com ) Two new studies show that combinations of medications taken by patients vary widely, making it extremely difficult to monitor or predict drug-drug interactions.The articles published in the January 2005 issue of the Journal of Psychiatric Practice found that virtually no two patients on more than one drug were taking the same combination of medications,which highlights the difficulty of monitoring for and predicting potentially dangerous drug-drug interactions.

The articles present the results of two studies of multiple medication use(MMU)in outpatients in the Veterans Affairs (VA) Healthcare System. MMU was found to increase as a function of both age and whether the patient was taking an antidepressant,with over a third of older patients on antidepressants taking eight or more medications.

The number of patients taking unique combinations of drugs (a combination different from any other patient in the sample) ranged from 70% in younger patients not taking antidepressants to 96% in older patients taking antidepressants.

These figures mean that no single prescriber can have extensive clinical experience with the combined effects of all of the medications his or her patients are taking, setting the stage for potentially adverse drug-drug interactions.

"The frequency and complexity of multiple medication use was surprising and troubling,"said Sheldon Preskorn,MD, principal investigator on the studies."It underscores the importance and the difficulty of avoiding complex and potentially dangerous drug-drug interactions."

The study results reinforce and extend the message of the recent Health, United States 2004 report from the Centers for Disease Control.The CDC reported that almost half of all Americans are taking at least one prescription drug, while, among those 65 years of age and older, five out of six are taking at least one medication and almost half are taking three or more.The CDC study also found that antidepressant use has almost tripled over the last decade, with 10% of adult women and 4% of men now taking antidepressants.

These results are also relevant to the issue of potentially dangerous drug-drug interactions--a problem that has been receiving increasing attention in recent years as highlighted by the withdrawal of drugs such as Vioxx and Seldane from the U.S. market.

The first study,Complexity of Medication Use in the Veterans Affairs Healthcare System: Part I.Outpatient Use in Relation to Age and Number of Prescribers,examined levels of medication use and complexity of drug regimens in a sample of 7,000 outpatients in Veterans Integrated Service Network 15 in the U.S. midwest.The investigators wanted to determine how use of multiple medications related to age and number of prescribers and if it was possible to identify frequently used medication combinations,in order to better predict and prevent adverse drug interactions.

The investigators found that,of the 5003 patients currently taking prescriptions medications,38% were receiving five or more drugs and 14% were taking eight or more.It was also not possible to identify commonly used medication combinations in this population.Almost three quarters of the patients were receiving a unique combination of drugs different from any other patient in the sample, and there was no single combination that occurred in even 1% of the patients.

The second study, Complexity of Medication Use in the Veterans Affairs Healthcare System: Part I.Antidepressant Use Among Younger and Older Outpatients,compared medication use in patients receiving antidepressant medications with patients not receiving antidepressants.The investigators found that patients receiving antidepressants were likely to be receiving significantly higher numbers of other medications than patients not taking antidepressants, with 24% of younger patients and 38% of older patients on antidepressants receiving eight or more medications (compared to 6% and 13% in those not receiving antidepressants).Again no single combination of medications occurred in even 1% of patients.

The large number of unique drug combinations involving antidepressants is especially troubling,since some antidepressants have significant potential to cause serious drug interactions.

The investigators strongly recommended more education for prescribers,pharmacists,healthcare organizations and patients about the complexity of drug prescribing and how it limits our ability to detect and prevent potential adverse drug interactions.They also advocated increased research to identify common medication combinations and evaluate their potential for adverse interactions as well as improved drug alert systems that are more capable of identifying potential problems involving multiple medications.