By THE NEW YORK TIMES

Most who enroll in clinical trials say they want to help themselves and others. But how can patients decide that a trial is worth their while?

Dr. Steven Goodman, professor of oncology in the division of biostatistics of the Johns Hopkins Kimmel Cancer Center, suggests asking doctors some questions:

¶Are there any other trials looking at this or other treatments for people like me here or elsewhere? If so, why should I enroll in this one?

¶Do you think the question being asked in this trial is important? Why or why not?

¶Has this question ever been studied before, and if so, what did those studies show?

¶Realistically, what do you think is the biggest difference likely to be seen in this trial, and how likely is that?

¶What do you think are the biggest downsides?

¶Who is paying for the trial?

¶Do you anticipate having any problem (or are you having problems) recruiting the necessary number of patients for this trial?

¶Would you recommend this trial to a relative?

20091029-2

LOOKING INSIDE This X-ray shows a mass in the upper lobe of the right lung. A clinical trial’s results are spurring a move toward maintenance therapy for lung cancer. 

 

By ANDREW POLLACK, For The New York Times

The newest prognosis for cancer may be longer chemotherapy.

Doctors and pharmaceutical companies are moving toward treating cancer patients with drugs continuously, even when they may not urgently need them. That would be a departure from the common practice of stopping treatment when the cancer is under control and resuming it only if the cancer worsens.

The strategy is called maintenance therapy – akin to periodic tune-ups aimed at preventing a car from breaking down. Doctors say it could prolong the time tumors are under control, helping to turn cancer into a chronic disease that is kept in check even if it is not cured.

While maintenance therapy is not entirely new, its use is growing, in part because some of the newer cancer drugs are more tolerable than the toxic ones of old and can be taken for longer periods.

At the recent annual meeting of the American Society of Clinical Oncology, for instance, doctors filled a huge auditorium for a debate on whether it is time to adopt maintenance therapy for lung cancer, the nation’s leading cause of cancer death. Other cancers for which maintenance therapy is being used or tried include ovarian cancer, multiple myeloma and non-Hodgkin’s lymphoma.

But some experts say that in many cases, the longer-term use of drugs has not been proved to prolong life.

Instead, it may just subject cancer patients to more side effects and tens of thousands of dollars in extra costs. There is also concern that tumors might become resistant to a drug used for a long time.

“Generally more is better, in both dose and potentially duration,” said Dr. Susan L. Kelley, chief medical officer of the Multiple Myeloma Research Foundation, which sponsors research on treatments for that disease. However, she said, “there are numerous kinds of cost to the patient, to the health system, to give these drugs over the longer term.”

Dr. Lawrence H. Einhorn, a professor at Indiana University, said much of the push for maintenance therapy was coming from pharmaceutical companies, which want their drugs “to be used as early as possible and as long as possible.”

And executives of these companies acknowledge that the therapy would mean bigger sales. “This is clearly a game-changing opportunity,” Brian P. Gill, vice president for corporate communications at Celgene, which is testing its drug Revlimid for maintenance treatment of multiple myeloma, told investors at a conference in March.

But the executives, and many doctors, say there is a good rationale for maintenance therapy.

Although treatment varies with the type of cancer, many patients now receive several initial cycles of chemotherapy. Then, if the cancer goes into remission, or even if the tumor simply stops growing, the therapy is stopped. It is resumed, usually with different drugs, only when the cancer starts worsening again.

That strategy evolved in part because the older chemotherapy drugs were so toxic that patients often needed to take a holiday from treatment.

“But if you think about it practically, you don’t really want to give the tumor a holiday,” said Colin Goddard, the chief executive of OSI Pharmaceuticals, which is trying to position its lung cancer drug Tarceva for use in maintenance therapy.

Some cancer patients welcome, or even demand, maintenance therapy, wanting to keep up the fight against their disease.

“I was one of those people who was frightened to stop chemo,” said Barbara Platzer, 71, of St. Louis, who has ovarian cancer.

So when her initial six cycles of chemotherapy ended with her cancer in remission, she enrolled in a clinical trial that provided her with 12 monthly maintenance treatments of an experimental drug called Xyotax. The results of the trial are not yet known, but Ms. Platzer’s cancer has remained in remission.

But Caryl Castleberry of Glen Ellen, Calif., who also has ovarian cancer, turned down maintenance therapy.

“I could hardly wait to be free from treatment, so the extra year they suggested was just not acceptable,” said Ms. Castleberry, 61, whose cancer has nonetheless remained in remission for six years.

Dr. Robert L. Coleman, an expert on ovarian cancer at the M. D. Anderson Cancer Center in Houston, said that because relapses tend to be fatal, there has been an urgent effort to prevent or delay them. But over the years, eight maintenance therapies failed in clinical trials.

Finally, a study published in 2003 showed that 12 monthly maintenance treatments of paclitaxel, a generic drug whose brand name is Taxol, delayed tumor progression by about seven months as compared with 3 monthly treatments with the same drug. But the difference in survival was not statistically significant, Dr. Coleman said, so there is still some debate about the merits of maintenance therapy for ovarian cancer.

For lung cancer, the move to maintenance therapy is being spurred by the results of a clinical trial of the drug Alimta that were presented at the oncology meeting in Orlando, Fla., in late May. Based on that trial, both the Food and Drug Administration and European regulators approved the use of Alimta for maintenance therapy earlier this month.

The trial, sponsored by Eli Lilly, which makes Alimta, involved 663 patients with advanced cancer whose tumors had shrunk or remained stable after the customary four cycles of initial chemotherapy. In typical practice, those patients would not be treated again unless their tumors resumed growing.

But in the trial, some patients got Alimta immediately after completing the initial, or first-line, chemotherapy. They lived a median of 13.4 months, significantly longer than the 10.6 months for those who got a placebo. And patients with the type of tumor for which Alimta works best lived a median of 15.5 months with maintenance therapy.

“This will change the treatment paradigm,” said Dr. Chandra P. Belani, deputy director of the Penn State Hershey Cancer Institute and the lead investigator in the trial.

But skeptics said the trial did not directly compare giving Alimta immediately with waiting until the tumor worsened. So it is not clear whether it was just the drug that provided the benefit, rather than the maintenance therapy. Two-thirds of the patients in the placebo group did get second-line therapy when their tumors worsened, but usually not with Alimta.

Alimta, also known as pemetrexed, costs about $4,000 per infusion given once every three weeks. Based on data from Lilly’s trials, patients getting the drug as maintenance therapy would receive an average of three more infusions than those getting the drug as second-line therapy.

Also, about 30 to 50 percent of lung cancer patients never get second-line chemotherapy, often because their condition worsens too much. So if Alimta were used as maintenance therapy, many more patients would get it.

For non-Hodgkin’s lymphoma, the drug used for maintenance is usually Rituxan, or rituximab, which is sold by Genentech and Biogen Idec.

A clinical trial showed that maintenance therapy with Rituxan did not help patients with an aggressive form of the disease. But a separate study, published recently in The Journal of Clinical Oncology, showed that it helped those with less aggressive forms of the disease.

After three years, cancer had not worsened for 68 percent of those who received the maintenance therapy. That was true for only 33 percent of those who did not receive the therapy. The survival difference was smaller, with 92 percent of those who got the maintenance therapy alive after three years compared with 86 percent of those who did not.

“We need more follow-up to see if it will improve overall survival,” said Dr. Thomas M. Habermann of the Mayo Clinic, an author of the study. Nevertheless, many doctors are giving patients maintenance treatment, usually four weekly infusions of Rituxan every six months for two years. That would cost about $30,000 a year.

For multiple myeloma, the drug being tried most often for maintenance therapy – Revlimid, or lenalidomide – is already being used for patients with relapses. It costs more than $6,000 a month and is taken as a once-a-day pill, making it particularly convenient for long-term use.

Right now it is used for an average of 10 months in the United States; with maintenance therapy that could grow to years, since remissions for multiple myeloma can last that long.

Trials are under way, but some doctors are not waiting. “We really need some randomized data to support it, but in the meantime it seems like a good idea,” said Dr. Brian G. M. Durie, chairman of the International Myeloma Foundation, an advocacy and research group that gets some financing from pharmaceutical companies.

Kevin, a graduate student with multiple myeloma, says he hoped a stem cell transplant would mark the end of his treatment. So he was taken aback when his doctor suggested taking Revlimid for two years as maintenance therapy as part of a clinical trial. He has been taking it a year so far, with some mild side effects like fatigue and upset stomach.

“I’m not enthusiastic about being on a drug like this indefinitely,” said Kevin, who spoke on the condition that his last name not be used because he did not want prospective employers to know about his illness. “But on the other hand, it’s a lot better than relapse.”

20091029-3

Ryan Collrd for The New York Times
RESEARCHER Chandra P. Belani led a lung cancer therapy clinical trial.

20091029-4

Brian Lee for The New York Times

Chuck Stauffer’s insurance covered hardly any of the cost of the cancer pills the doctor prescribed for him to take at home. 

 

By ANDREW POLLACK For The New York Times

Chuck Stauffer’s insurance covered the surgery to remove his brain tumor. It covered his brain scans. And it would have paid fully for tens of thousands of dollars of intravenous chemotherapy at a doctor’s office or hospital.

But his insurance covered hardly any of the cost of the cancer pills the doctor prescribed for him to take at home. Mr. Stauffer, a 62-year-old Oregon farmer, had to pay $5,500 for the first 42-day supply of the drug, Temodar, and $1,700 a month after that.

“Because it was a pill,” he said, “I had to pay – not the insurance.”

Pills and capsules are the new wave in cancer treatment, expected to account for 25 percent of all cancer medicines in a few years, up from less than 10 percent now.

The oral drugs can free patients from frequent trips to a clinic to be hooked to an intravenous line for hours. Fewer visits might save the health system money as well as time. And the pills are a step toward making cancer a manageable chronic condition, like diabetes.

But for many patients, exchanging an I.V. bag for a pill is a lopsided trade because the economics and practice of cancer medicine have not caught up with the convenience of oral drugs.

Start with the double ledger of drug insurance. Drugs that are infused at a clinic are typically paid for as a medical benefit, like surgery. Pills, though, are usually covered by prescription drug plans, which are typically much less generous; for expensive cancer pills, patients might face huge co-payments or quickly exceed an annual coverage limit. Sometimes, as in Mr. Stauffer’s case, a single insurer is involved.

Many times, though, a separate company – a so-called pharmacy benefit manager – provides the prescription drug coverage.

The growing use of cancer pills is also thrusting patients and doctors into new roles they have not yet fully mastered. Without a physician’s direct supervision, side effects can be missed. Some patients do not take all their medicine, raising the risk their cancer will worsen. Others take too many pills, risking toxic reactions.

For doctors, the new drugs also pose financial challenges. Physicians can profit from infusing drugs in their offices but not from writing prescriptions that are filled at a pharmacy.

With oral cancer drugs, “the technology has outstripped the ability of society to integrate it into the mainstream in a smooth fashion,” said Carlton Sedberry, a pharmacy expert at Medical Marketing Economics, a consulting firm.

Oregon, partly in response to Mr. Stauffer’s case, has passed a law requiring insurance companies to provide equivalent coverage of oral and intravenous cancer drugs. Some other states are now considering similar measures.

So far the health reform debate in Washington has not drilled into specifics like cancer pill coverage.

Infused drugs, of course, can also be frightfully expensive and under some insurance plans – including Medicare – can carry big co-payments. But it is the oral drugs that seem to be causing a disproportionate number of financial problems for cancer patients. The Patient Advocate Foundation, an organization that helps people make insurance co-payments for cancer drugs, says oral medicines accounted for 56 percent of the cases in which it helped Medicare patients last year, even though far more cancer patients were on intravenous drugs.

One oncology practice in central Pennsylvania has a nurse assigned full time to dealing with patients on oral drugs and arranging insurance or charity payments for the pills. “Trying to obtain this drug for the patient – that’s my struggle, every single day,” said the nurse, Jane Flenner.

Although drug makers are developing oral versions of some infused cancer medications, most of the new pills and capsules have no intravenous equivalent.

The oral exemplar is Gleevec from Novartis, which since its approval in 2001 has helped turn chronic myeloid leukemia as well as gastrointestinal stromal tumors into manageable diseases for many patients.

Douglas Jenson, 75, of Canby, Ore., has taken Gleevec for 10 years for leukemia. He goes for a blood test once every three months and sees his oncologist every six months, but is healthy enough to go whitewater rafting.

Making it even easier, Mr. Jenson gets his Gleevec free because he participated in an early clinical trial of the drug. Otherwise it would cost more than $40,000 a year.

While Mr. Jenson has been diligent about taking his five capsules every day at lunchtime, research indicates that many patients on the oral drugs do not consistently take the proper dose. One study, for example, found that Gleevec patients, on average, were taking only 75 percent of their prescribed doses.

Some cancer patients skip pills or stop taking them completely – whether because of costs, forgetfulness, side effects, complicated regimens or other factors.

“When I first started looking into this, I thought, ‘People with cancer have too much to lose, how can they not take their drugs?’ ” said Dr. Ann Partridge, an oncologist at Dana-Farber Cancer Institute in Boston.

Some other cancer patients, meanwhile, end up taking too many pills.

Gayne Ek of Allen, Tex., said he once skipped all of his Gleevec capsules for six weeks. Then, with the stockpile of capsules he accumulated, he took twice the prescribed dose for six weeks, hoping it would be more effective. It was not.

For many patients, though, the main challenge is not taking their pills, but paying for them. Under Medicare, most oral cancer drugs are covered by the Part D prescription drug program, which has a 25 percent co-payment. It also has the annual “doughnut hole” – reached when a patient’s total drug costs hit $2,700, after which the patient must shoulder the next $3,000 or so before coverage resumes.

Mary Francis Thomas of Camp Hill, Pa., reached the doughnut hole on her very first prescription of the year. Ms. Thomas, 86, had to pay $4,300 in January for a month’s supply of Revlimid, to treat a disorder that can lead to leukemia. Having now passed through the doughnut hole, she must pay 5 percent of the cost of the drug for the rest of the year – which still works out to $377 a month.

Drug companies say they provide free drugs for some patients and give money to charities for co-payment assistance. And Lee Newcomer, senior vice president for oncology at UnitedHealthcare, the big insurer, said many commercial policies capped total annual out-of-pocket expenditures, so patients should not have huge co-payments month after month.

But nurses and patient advocates say that many patients still have trouble paying for the drugs.

Mr. Stauffer, the Oregon farmer, is no longer one of them, though. After his daughter, Heather Kirk, told his story to Peter Courtney, the president of the state senate, Oregon enacted in late 2007 the nation’s first state law requiring insurers to provide equivalent reimbursement for oral and intravenous chemotherapy drugs.

Mr. Stauffer’s insurer, Regence Blue Cross Blue Shield, even reimbursed him for the money he had already spent on Temodar. Several other states, including Colorado, Hawaii, Minnesota, Montana, Oklahoma and Washington, are now considering similar legislation.

By NICHOLAS BAKALAR  For The New York Times

If you think your doctor will automatically tell you if you have an abnormal test result, think again. Researchers studying office procedures among primary care physicians found evidence that more than 7 percent of clinically significant findings were never reported to the patient.

The scientists, led by Dr. Lawrence P. Casalino, an associate professor at Weill Cornell Medical College, reviewed the records of 5,434 patients at 19 independent primary care practices and four based in academic medical centers. They extracted records that contained abnormal results for blood tests or X-rays and other imaging studies, and then searched for documentation that the patient had been properly informed of the problem in a timely way.

Then they surveyed the doctors with uninformed patients. Some told them that the patient had been informed, even though there was no documentation, while others believed the results were not significant and therefore required no notification. In a few cases, the doctor said that the patient had not yet been informed but soon would be. After accounting for these and other ambiguous cases, the researchers found that of 1,889 abnormal results, there were 135 failures to inform.

Results varied widely among the primary care practices, and all but the smallest – those with fewer than eight doctors – had at least one failure. In two of the largest academic medical centers, with a combined 80 primary care specialists, 23 percent of abnormal results were never mentioned to the patients.

Dr. Eric G. Poon, director of clinical informatics at Brigham and Women’s Hospital in Boston, who was not involved in the work, said it was a high-quality study with good methodology. “You go to the doctor and you get tests and assume that there is a right way for the doctor to look at the results and to act on them quickly,” he said. “But the truth of the matter is that a lot of things can fall through the cracks. Information is handed down from one person to another to another before the doctor actually sees it.”

Unsurprisingly, practices that used electronic medical records had lower failure rates than those that used only paper documents. But offices that used a combination of paper and computer records had the worst results of all.

Using information from a study of the literature and an earlier pilot study, the authors concluded that following five relatively simple procedures could eliminate most errors: results are routed to the responsible doctor, the doctor signs off on them, the office informs patients of all results, the practice documents that patients have been informed, and finally patients are told to call after a certain time interval if they have not learned the results of their tests. Most practices examined in the current study, published Monday in The Archives of Internal Medicine, failed to follow those steps.

The authors acknowledge that their sample was self-selected – offices volunteered to participate – and included only 23 practices. A random sample of offices, or a larger number of them, they write, could have produced different results.

Although some doctors may have informed their patients without documenting it, Dr. Casalino said that failure to document is almost as bad as failing to inform. “If what happens doesn’t get documented,” he said, “it can be very confusing when the patient next needs to be taken care of.”

For patients, Dr. Casalino said, the message is simple. “Don’t assume that ‘no news is good news’ when you have tests done. That’s a very dangerous assumption. If you’ve had a test done and you don’t hear about it after a week or two goes by, call the doctor’s office.”

20091028-1

By TR Editors

MIT Technology Review, November/December 2009Interventions for autism are most successful if they begin between two and four years of age, but the average age at diagnosis is nearly six. The LENA Foundation has developed a screening system that can be used with children as young as two. The child wears a digital recorder all day long. After recording up to 16 hours of audio, parents mail the recorder back to the foundation, where software is used to comb through the child’s vocalizations in search of patterns that indicate a high risk of autism. Parents are advised to consult a specialist if such patterns are found. The foundation says the tool can detect autism in children with the disorder in 91 cases out of 100.

Product: LENA Language and Autism Screen

Cost: $200

Availability: Now

Source: www.lenababy.com

Company: LENA Foundation

GoogleNews.com, October 27, 2009, by H Josef Hebert (AP)  —  WASHINGTON – The Obama administration is giving a jolt to the futuristic “smart” electric grid, hoping to more quickly bring America’s power transmission system into the digital age.

President Barack Obama, during a visit to a solar energy facility in Arcadia, Fla., is announcing Tuesday that he is making available $3.4 billion in government support for 100 projects aimed at modernizing the power grid. The projects include installing “smart” electric meters in homes, automating utility substations, and installing thousands of new digital transformers and grid sensors.

White House officials provided details of the initiative prior to the president’s scheduled visit to Florida Power & Light Co.’s DeSoto Next Generation Solar Energy Center, the largest photovoltaic electricity facility in the country.

Officials have argued that a more modern grid is needed to give consumers better control over their electricity usage and costs, and to spur development of renewable energy sources such as wind and solar.

The $3.4 billion in grants from the government’s economic stimulus program will be matched by $4.7 billion in private investments, the officials said. The smallest grant will be $400,000 and the largest $200 million.

“We have a very antiquated (electric grid) system in our country,” said Carol Browner, assistant to the president for energy and climate change. “The current system is outdated, it’s dilapidated.”

Browner said the federal funding will spur the needed modernization of the grid and set the stage for the smooth introduction of large amounts of electricity from wind or solar sources into the transmission system.

Matt Rogers, the Energy Department official involved in the program, said the 100 projects were selected from 400 proposed. The money would be distributed over the next two months and the work is expected to be done over the next one to three years, he said.

The push to essentially bring modern computer and communications technology to the electric grid has been under way for some time but has gained momentum with the prospect of billions of dollars in federal support.

Rogers said the government funds will allow installation of 18 million smart meters and 1 million other in-home devices as well as more modern thermostats to allow homeowners to better monitor their electricity usage. The government and industry want to deploy 40 million smart meters – wall-based units that can monitor how much electricity various appliances use and turn them off when energy is costlier to consume – within the next several years.

Other projects funded under the program will result in the installation of 850 sensors to allow utilities to better monitor the grid; the installation of 200,000 digital transformers to reduce the risk of power outages; and the automation of 700 grid substations.

“This will save or create tens of thousands of jobs,” said Jared Bernstein, chief economist and economic adviser to Vice President Joe Biden. He said the jobs will include equipment installers and electrical engineers as well as communications systems analysts and data entry clerks.

A $200 million grant will go to Energy Smart Florida, a program involving Florida Power & Light that plans to install 2.6 million smart meters in homes and advanced monitoring systems in the grid substations, said Browner.

“The impact of this will be felt throughout Florida,” she said.

20091027-5

20091027-4

SOURCE: American Psychological Association | PHOTO: iStockphoto | GRAPHIC: The Washington Post

GoogleNews.com, Washington Post, by Lindsay Tanner  —  Groundbreaking research suggests genes help explain why some people can recover from a traumatic event while others suffer post-traumatic stress disorder. Though preliminary, the study provides insight into a condition expected to strike increasing numbers of military veterans returning from combat in Iraq and Afghanistan, one health expert said.

Researchers found that specific variations in a stress-related gene appeared to be influenced by trauma at a young age _ in this case child abuse. That interaction strongly increased the chances for adult survivors of abuse to develop signs of PTSD.

Among adult survivors of severe child abuse, those with the specific gene variations scored more than twice as high (31) on a scale of post-traumatic stress, compared with those without the variations (13).

The worse the abuse, the stronger the risk in people with those gene variations.

The study of 900 adults is among the first to show that genes can be influenced by outside, nongenetic factors to trigger signs of PTSD. It is the largest of just two reports to show molecular evidence of a genetic influence on PTSD.

“We have known for over a decade, from twin studies, that genetic factors play a role in vulnerability to developing PTSD, but have had little success in identifying specific genetic variants that increase risk of the disorder,” said Karestan Koenen, a Harvard psychologist doing similar research. She was not involved in the new study.

The results suggest that there are critical periods in childhood when the brain is vulnerable “to outside influences that can shape the developing stress-response system,” said Emory University researcher and study co-author Dr. Kerry Ressler.

The study appears in Wednesday’s Journal of the American Medical Association. Several study authors, including Ressler, reported having financial ties to makers of psychiatric drugs.

Ressler noted that there are probably many other gene variants that contribute to risks for PTSD, and others may be more strongly linked to the disorder than the ones the researchers focused on.

Still, he and outside experts said the study is important and that similar advances could lead to tests that will help identify who’s most at risk. Treatments including psychotherapy and psychiatric drugs could be targeted to those people, Ressler said.

About a quarter of a million Americans will develop PTSD at some point in their lives after being victimized or witnessing violence or other traumatic events. Rates are much higher in war veterans and people living in high-crime areas.

Symptoms can develop long after the event and usually include recurrent terrifying recollections of the trauma. Sufferers often have debilitating anxiety, irritability, insomnia and other signs of stress.

Dr. Thomas Insel, director of the National Institute of Mental Health, said the study is particularly valuable for the light it sheds on military veterans, who are known to be vulnerable to PTSD.

He said the results help explain differences in how two people see the same roadside bomb blast. One simply experiences it as “a bad day but goes back and is able to function.” The other later develops paralyzing stress symptoms.

“This could be quite a wave that will hit us over the months and years ahead,” Insel said. His agency paid for the study.

Study participants were mostly low-income black adults, aged 40 on average, who sought non-psychiatric health care at a public hospital in Atlanta. They were asked about experiences in childhood and as adults and gave saliva samples that underwent genetic testing.

Almost 30 percent of participants reported having been sexually or physically abused as children. Most also had experienced trauma as adults, including rape, attacks with weapons and other violence.

Researchers focused on symptoms of PTSD rather than an actual diagnosis, and found that about 25 percent had stress symptoms severe enough to meet criteria for the disorder, Ressler said.

Childhood abuse and adult trauma each increased risks for PTSD symptoms in adulthood. But the most severe symptoms occurred in the 30 percent of child abuse survivors who had variations in the stress gene.

Researchers were not able to determine if the symptoms were reactions to the child abuse or to the more recent trauma _ or both, said co-author Rebekah Bradley, also of Emory University.

The study is an important contribution to a growing body of research showing how severe abuse early in life can have profound, lasting effects, said Duke University psychiatry expert John Fairbank, co-director of the National Center for Child Traumatic Stress. He was not involved in the research.

http://jama.ama-assn.org/cgi/content/abstract/302/15/1651
JAMA – Vol 302, Number 15, October 21, 2009

A Randomized Controlled Trial

Robert M. Carney, PhD; Kenneth E. Freedland, PhD; Eugene H. Rubin, MD, PhD; Michael W. Rich, MD; Brian C. Steinmeyer, MS; William S. Harris, PhD

JAMA. 2009;302(15):1651-1657.

Context  Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids.

Objective  To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD).

Design, Setting, and Participants  Randomized controlled trial. Between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD were randomized.

Interventions  After a 2-week run-in period, all patients were given 50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10 weeks.

Main Outcome Measures  Scores on the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HAM-D).

Results  Adherence to the medication regimen was 97% or more in both groups for both medications. There were no differences in weekly BDI-II scores (treatment x time interaction = 0.02; 95% confidence interval [CI], -0.33 to 0.36; t112 = 0.11; P = .91), pre-post BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5 to 2.0; t116 = -0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, -2.2 to 2.4; t115 = 0.12; P = .90). The groups did not differ on predefined indicators of depression remission (BDI-II 8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t113 = -0.11; P = .91) or response (>50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t112 = 0.15; P = .88).

Conclusions  Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined.

Trial Registration  clinicaltrials.gov Identifier: NCT00116857
Author Affiliations: Departments of Psychiatry (Drs Carney, Freedland, and Rubin and Mr Steinmeyer) and Medicine (Dr Rich), Washington University School of Medicine, St Louis, Missouri; and Cardiovascular Health Research Center, Sanford Research, University of South Dakota, Sioux Falls (Dr Harris).

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