Could intranasal oxytocin be used to enhance relationships?

Research imperatives, clinical policy, and ethical considerations

By O. A. Wudarczyk, B. D. Earp, A. J. Guastella & J. Savulescu

Abstract

Purpose of review. 

Well-functioning romantic relationships are important for long-term health and well-being, but they are often difficult to sustain. This difficulty arises (in part) because of an underlying tension between our psychobiological natures, culture/environment, and modern love and relationship goals. One possible solution to this predicament is to intervene at the level of psychobiology, enhancing partners’ interpersonal connection through neurochemical modulation. This article focuses on a single, promising biobehavioral sub-system for such intervention: the attachment system, based largely upon the expression of the neuropeptide oxytocin. Could the exogenous administration of oxytocin—under the right conditions—be used to facilitate relational or marital well-being?

Recent findings.

If so, it would require considerable forethought. Recent research complicates the popular image of oxytocin as a universal social enhancer or ‘love hormone’ and shows that it may exert a variety of different effects, at different dosages, on different people, under different circumstances. Accordingly, we discuss what is known about oxytocin, including its“good” and “bad” effects on human behavior and on higher-order functional processes.

Summary.

Building upon animal-model, human preclinical, and clinical findings, we outline a proposal for the use of oxytocin in the therapeutic neuroenhancement of contemporary romantic relationships. Highlighting key targets for future research along the way, we then conclude by discussing some of the clinical and ethical considerations that would pertain to the implementation of this knowledge in applied settings.

Key Points

* Intranasal oxytocin may hold promise for the therapeutic neuroenhancement of modern relationships. Oxytocin has “good” and “bad” effects, however, that may be different for different individuals and couples depending upon a range of personal, interpersonal, and contextual factors.

* Large-scale clinical trials with adequate sample sizes, and that include both males and females, are needed to fill in a range of “gaps” in existing knowledge. Chronic administrations and ecologically valid study designs should be top research priorities.

* The imminent prospect of neurochemical modulation of interpersonal relationships should inspire the development of general ethical guidelines for the responsible use of such technology. These guidelines should emphasize autonomy, consent, and personal and interpersonal well-being.

* As is the case with any new area of biomedical research, practical, moral, and clinical-policy considerations must be addressed in tandem with any progress made on scientific and theoretical fronts.

The entire article is here.

Dangers found in lack of safety oversight for Medicare drug benefit

By Tracy Weber, Charles Ornstein and Jennifer LaFleur
ProPublica
Originally published: May 11, 2013

Here is an excerpt:

But an investigation by ProPublica has found the program, in its drive to get drugs into patients’ hands, has failed to properly monitor safety. An analysis of four years of Medicare prescription records shows that some doctors and other health professionals across the country prescribe large quantities of drugs that are potentially harmful, disorienting or addictive for their patients. Federal officials have done little to detect or deter these hazardous prescribing patterns.

Searches through hundreds of millions of records turned up physicians such as the Miami psychiatrist who has given hundreds of elderly dementia patients the same antipsychotic, despite the government’s most serious “black box” warning that it increases the risk of death. He believes he has no other options.

Some doctors are using drugs in unapproved ways that may be unsafe or ineffective, records showed. An Oklahoma psychiatrist regularly prescribes the Alzheimer’s drug Namenda for autism patients as young as 12; he says he thinks it calms them. Autism experts said there is scant scientific support for this practice.

The entire article is here.

Ethical and practical implications of financial conflicts of interest in the DSM-5

By Lisa Cosgrove and Emily Wheeler
doi: 10.1177/0959353512467972
Feminism Psychology
February 2013 vol. 23 no. 1 93-106

Abstract

The revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM), scheduled for publication in May 2013 by the American Psychiatric Association (APA), has created a firestorm of controversy because of questions about undue industry influence. Specifically, concerns have been raised about financial conflicts of interest between DSM-5 panel members and the pharmaceutical industry. The authors argue that current approaches to the management of these relationships, particularly transparency of them, are insufficient solutions to the problem of industry’s capture of organized psychiatry. The conceptual framework of institutional corruption is used to understand psychiatry’s dependence on the pharmaceutical industry and to identify the epistemic assumptions that ground the DSM’s biopsychiatric discourse. APA’s rationale for including premenstrual dysphoric disorder in the DSM-5 as a Mood Disorder is reviewed and discussed.

Thanks to Ken Pope for sharing this abstract.

Elderly Patients Routinely Prescribed Risky Drugs

By Anahad O'Connor
The New York Times - Well Column
Originally published April 15, 2013

Doctors in the United States routinely prescribe potentially harmful drugs to older patients, and the problem is particularly acute in the South, a new study shows.

The analysis found that more than one in five seniors on Medicare in the South were prescribed medications that health authorities have specifically advised doctors to avoid giving to older patients because of their severe side effects. Compared with people 65 and older living in New England, those living in the southern region from Texas to South Carolina were about 12 percent more likely to be prescribed a high-risk medication.

The researchers suspected that factors like education, socioeconomic status and access to quality medical care might be driving some of the regional differences. And to some extent, that appeared to be the case. As socioeconomic status grew lower, for example, the likelihood of being prescribed a high-risk drug increased. But even after accounting for these factors, the researchers found that the disparity persisted.

The entire story is here.

What Doctors Don't Know about the Drugs They Prescribe

Psychiatrists Top List of Big Pharma Payments Again

By Deborah Brauser
Medscape Medical News
Originally published March 14, 2013

Once again, psychiatrists top the updated Dollars for Docs list of large payments from pharmaceutical companies to individual US clinicians.

On March 12, the investigative journalism group ProPublica released the names of the 22 physicians who, since 2009, received more than $500,000 from these companies in speaking and consulting fees. Mirroring the organization's first report released in 2010, psychiatrists dominate the list.

This time, the top recipient was Jon Draud, MD, medical director of the psychiatric and addiction medicine program at Baptist Hospital in Nashville, Tennessee, and from the Middle Tennessee Medical Center in Murfreesboro.

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APA Reaction

"My immediate, honest response was that this boggles the mind," James Scully, MD, CEO of the American Psychiatric Association (APA), told Medscape Medical News.

The entire story is here.

Thanks to Ed Zuckerman for this story.

Indictment Of Manhattan Doctor Who Sold Oxycodone Prescriptions To Drug Dealers

Attorney General of New York Press Release
Originally released on February 13, 2013

Attorney General Eric T. Schneiderman today announced a 55-count indictment against Dr. David Brizer on charges he sold prescriptions for oxycodone and other powerful pain medications to drug dealers from his Rockland County and Midtown Manhattan offices. The indictment also charges Brizer with illegally possessing controlled substances and underreporting his income by at least $500,000 on his New York State personal tax returns in 2010 and 2011.

Brizer, a psychiatrist, was arraigned in Rockland County Court today on two top counts of Criminal Tax Fraud; 34 counts of Criminal Sale of a Prescription for a Controlled Substance; 15 counts of Criminal Possession of a Controlled Substance; 2 counts of Offering a False Instrument for Filing; along with Scheme to Defraud and Conspiracy charges. All are felony counts. He faces up to seven years behind bars.

“Instead of saving lives, Dr. Brizer used his position to supply drug dealers and feed a prescription drug epidemic that is devastating families across our state. The message is clear – whether you are a doctor or a criminal on the street, my office will prosecute those profiting off the cycle of abuse,” Attorney General Schneiderman said. “This office will use every tool at our disposal to bring criminal charges against those who line their own pockets by fueling dangerous addictions and illegally trafficking in prescription narcotics.”

The entire news release is here.

Pfizer disputes claim against antidepressant

By Linda Johnson
Associated Press
Originally published January 31, 2013

The maker of Zoloft is being sued in an unusual case alleging the popular antidepressant has no more benefit than a dummy pill and that patients who took it should be reimbursed for their costs.

Zoloft's maker, Pfizer Inc., the world's biggest drugmaker by revenue, disputes the claim, telling the Associated Press Thursday that clinical studies and the experience of millions of patients and their doctors over two decades prove Zoloft is effective.

The lawsuit was described as frivolous by Pfizer and four psychiatry experts interviewed by the AP.

Not so, according to plaintiff Laura A. Plumlee, who says Zoloft didn't help her during three years of treatment. Her attorney, R. Brent Wisner of the Los Angeles firm Baum Hedlund Aristei Goldman, argues the Food and Drug Administration shouldn't have approved Zoloft because Pfizer didn't publish some clinical studies that found the drug about as effective as a placebo.

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Kirsch, associate director of Harvard Medical School's Program in Placebo Studies, has published a book and several medical journal articles on the effect. With colleagues, he reviewed numerous studies of popular antidepressants, including unpublished studies obtained using the Freedom of Information Act.

"The difference between drug and placebo is very small," below the level that benefits patients, Kirsch concluded.

He said Pfizer produced two studies showing Zoloft worked better than placebo — the FDA's requirement for approval — but most Zoloft studies showed its effect was the same as a placebo.
Dr. Michael Thase, who heads the mood and anxiety disorders program at the University of Pennsylvania's medical school, said research by others using the same unpublished studies concluded antidepressants have "a modest effect over placebo," on average about 15 percentage points.

That's partly because the rate of study participants improving when they're taking a placebo has been rising, said New York University's Sussman.

The entire story is here.

A Recent Study of Atypical Neuroleptics: “The Results of our Study are Sobering”

Sandra Steingard, M.D.
Mad In America
Originally published December 3, 2012


This week, MIA highlighted a recently published study of the four most commonly prescribed neuroleptics.  As noted in the post, the major outcome was that these drugs were not found to be effective or safe.

This important study, co-authored by Dilip Jeste the current president of the American Psychiatric Association, is worth reviewing in greater detail.

The study was modeled to capture clinical practice.  Entry to the study was broad and not limited to a specific diagnostic category.  It is characterized as a study of “older adults” and I admit to some chagrin that this meant anyone over 40.  Diagnoses included schizophrenia, schizoaffective disorder,  and psychosis associated with mood disorder, PTSD or dementia.  It was open to individuals who were either already taking an atypical neuroleptic or had a psychiatrist who was recommending this.

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What was most striking to me is this line from the study: there was

“no significant change in psychopathology with any of the study atypical antipsychotics“

They did not even report the numbers in their report.

The entire information is here.

Thanks to Tom Fink for this information.

Heart risk link to SSRI antidepressants confirmed

BBC Health News
Originally posted January 30, 2013

Some but not all antidepressant drugs known as SSRIs pose a very small but serious heart risk, say researchers.

Citalopram and escitalopram, which fall into this drug group, can trigger a heart rhythm disturbance, a new study in the British Medical Journal shows.

UK and US regulators have already warned doctors to be extra careful about which patients they prescribe these medicines to.

And they have lowered the maximum recommended dose.

The UK's Medicines and Healthcare products Regulatory Agency (MHRA) says people with pre-existing heart conditions should have a heart trace before going on these drugs, to check for a rhythm disturbance known as long QT interval.

Experts reassure that complications are very rare and that in most cases the benefits for the patient taking the drug will outweigh the risks.

The entire story is here.

Thanks to Tom Fink for this story.

A Clinical Trial and Suicide Leave Many Questions: Part 4: The University of Minnesota’s Response

By Judy Stone | January 8, 2013
Scientific American

Demystifying drug development, clinical research, medicine, and the role ethics plays

In earlier posts, we’ve looked at issues of consent, investigator responsibilities, and conflicts of interest on the case of Dan Markingson’s suicide while participating in a clinical trial of anti-psychotics at the University of Minnesota. This time, we turn to the University’s response.

 Not surprisingly, the University has claimed it has no responsibility for any wrongdoing—that in fact, no wrongdoing even occurred. But there are some inconsistencies in the story and unanswered questions. There is also concern over how the University has responded to criticism. We’ll examine these issues in this post.

Background regarding the University’s response

In response to the Minnesota Board of Social Work’s “corrective action” vs. Jeanne Kenney, the social worker/study coordinator who did most of the study assessments on Markingson, the UMN’s General Counsel Mark Rotenberg stated, “As we’ve stated previously, the Markingson case has been exhaustively reviewed by federal, state and academic bodies since 2004. The FDA, the Hennepin County District Court, the Minnesota Board of Medical Practice, the Minnesota Attorney General’s Office and the University’s Institutional Review Board have all reviewed the case. None found fault with the University. None found fault with any of our faculty. Most importantly, none found any causal link between the CAFE trial and the death of Mr. Markingson.”

Yet a number of UMN faculty have remaining concerns and have requested an independent investigation. Two years ago, eight faculty members in the Bioethics Department wrote Rotenberg, citing the University’s conflicts of interest in the matter. The UMN declines to reexamine the case, saying that they have been exonerated. In October 2012, Dr. Carl Elliott, Professor in the UMN Center for Bioethics, wrote Dr. Debra DeBruin, director of the Clinical Research Ethics Consultation Service for the UMN Clinical and Translational Science Institute, again requesting a review. This time Dr. Elliott expressed concern regarding human subjects protections in other trials conducted by the psychiatry department as well. As always, Dr. Elliott’s concerns were thoroughly documented. Once again, the University has turned away.

The entire story is here.

Thanks to Tom Fink for this story.

Amgen Agrees to Pay $762 Million for Marketing Anemia Drug for Off-Label Use

By ANDREW POLLACK and MOSI SECRET
The New York Times
Published: December 18, 2012

The biotechnology giant Amgen marketed its anemia drug Aranesp for unapproved uses even after the Food and Drug Administration explicitly ruled them out, federal prosecutors said on Tuesday.

The federal charges were made public as Amgen pleaded guilty to illegally marketing the drug and agreed to pay $762 million in criminal penalties and settlements of whistle-blower lawsuits.

Amgen was “pursuing profits at the risk of patient safety,” Marshall L. Miller, acting United States attorneyin Brooklyn, said in a telephone news briefing on Tuesday.

David J. Scott, Amgen’s general counsel, entered the guilty plea at the United States District Court in Brooklyn to a single misdemeanor count of misbranding the drug, Aranesp, meaning selling it for uses not approved by the F.D.A.

Amgen agreed to pay $136 million in criminal fines and forfeit $14 million, with about $612 million going to settle civil litigation.

The entire article is here.

Drug Executive Faces Manslaughter Charges

By SCOTT SAYARE
The New York Times
Published: December 11, 2012

A French court brought manslaughter and injury charges on Tuesday against a drug executive and six companies in a case involving a diabetes and weight-loss drug that caused cardiovascular damage, the Paris public prosecutor’s office said.

The executive, Jacques Servier, 90, and six companies of the Servier group are accused of having known the risks associated with the drug, Mediator, which they produced and marketed until French authorities ordered it withdrawn in 2009, the spokeswoman, Agnès Thibault-Lecuivre, said.

The entire article is here.

Supreme Court slates generic drug 'pay-for-delay' case

By Joe Carlson
ModernHealthcare.com
Posted: December 8, 2012

The U.S. Supreme Court has agreed to hear arguments in a "pay-for-delay" case that has the Federal Trade Commission accusing generic drugmakers of violating competition laws by agreeing to accept $42 million in annual payments in exchange for not selling generic versions of a more-expensive brand-name testosterone gel.

The FTC says (PDF) the companies—lead respondent Watson Pharmaceuticals, along with Paddock Laboratories, Par Pharmaceutical Cos. and Abbott Laboratories subsidiary Solvay Pharmaceuticals—conspired illegally to keep cheaper drugs off the market, to the detriment of consumers of the brand-name drug.

The companies, meanwhile, say their actions were legal and immune from FTC scrutiny (PDF). However, they did not oppose a hearing before the U.S. Supreme Court, because they said differing interpretations of federal law had led to split legal reasoning in various U.S. circuits on a controversy of national significance.

The entire story is here.

Court: Off-Label Drug Marketing Is 'Free Speech'

By John Fauber, Reporter
Milwaukee Journal Sentinel/MedPage Today
Originally Published: December 04, 2012


A decision by a federal appeals court this week could have a dramatic impact on the marketing of prescription drugs in America, potentially affecting patient care and everything from TV advertising to future government prosecutions which, in the past, had yielded billions of dollars in settlements, doctors and attorneys said Tuesday.

"This risks taking us back to an era when people could promote snake oil without restrictions – a situation I would hate to see," said Richard Deyo, MD, a professor of family medicine at Oregon Health and Science University.

Citizens United Redux

However, others say the ruling by a three-judge panel of the Court of Appeals for the Second Circuit in Manhattan is a victory for free speech, one that could become the drug industry equivalent of Citizens United, the 2010 U.S. Supreme Court decision that gave corporations and unions the right to spend unlimited sums on political ads.

Like the Citizens United case, the ruling Tuesday by the prestigious U.S. Court of Appeals for the Second Circuit in New York, involved the right of commercial free speech, applying it to the complicated world of pharmaceutical industry promotion of prescription drugs.

How wide-ranging the decision becomes likely will depend on whether it gets to the U.S. Supreme Court, attorneys said.

Once the Food and Drug Administration approves a drug, physicians are free to prescribe that drug as they wish -- but the drug makers can only market the drug for the FDA-approved marketing indication.

The case involves Alfred Caronia, a sales representative with Orphan Medical who was criminally prosecuted for making off-label promotional statements about Xyrem, a drug approved in 2002 to treat narcolepsy patients with a condition known as cataplexy. Cataplexy involves weak or paralyzed muscles.

The FDA required a black box warning on the drug stating that its safety and effectiveness had not been established in people under the age of 16. The active ingredient in Xyrem is GHB, is a powerful medication that acts on the central nervous system and also is known as the "date rape" drug.

The entire story is here.

New psychiatric drugs low priority for pharmaceutical firms

CBC News
Originally posted October 12, 2012

The pharmaceutical industry has largely abandoned drug development for mental illnesses even though depression is a leading cause of disability, experts say.

Authors of papers published in this week's issue of the journal Science Translational Medicine argue that drug discovery for treating psychiatric disorders such as autism, schizophrenia, bipolar disorder and depression are at a near standstill.

"Antipsychotics and antidepressants have been some of the most profitable agents for companies over the last two decades," said Dr. Thomas Insel, director of the U.S. National Institute of Mental Health and one of the authors.

"But that doesn't mean they're effective. What it means is that they sell and they can be marketed."

In the last five decades, more than 20 antipsychotics and 30 antidepressants have been marketed with over $25 billion in sales in the U.S. in 2011 alone, Insel said.

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"The central problem is clear: Neither vast unmet medical need, nor large and growing markets, nor concerted sales campaigns that attempt to recast 'me-too drugs' as innovative can illuminate a path across very difficult scientific terrain," Hyman wrote.

The entire story is here.

Attention Disorder or Not, Pills to Help in School

By ALAN SCHWARZ

The New York Times

Originally published October 9, 2012

Here is an excerpt:

Dr. Anderson is one of the more outspoken proponents of an idea that is gaining interest among some physicians. They are prescribing stimulants to struggling students in schools starved of extra money — not to treat A.D.H.D., necessarily, but to boost their academic performance.

It is not yet clear whether Dr. Anderson is representative of a widening trend. But some experts note that as wealthy students abuse stimulants to raise already-good grades in colleges and high schools, the medications are being used on low-income elementary school children with faltering grades and parents eager to see them succeed.

“We as a society have been unwilling to invest in very effective nonpharmaceutical interventions for these children and their families,” said Dr. Ramesh Raghavan, a child mental-health services researcher at Washington University in St. Louis and an expert in prescription drug use among low-income children. “We are effectively forcing local community psychiatrists to use the only tool at their disposal, which is psychotropic medications.”

Dr. Nancy Rappaport, a child psychiatrist in Cambridge, Mass., who works primarily with lower-income children and their schools, added: “We are seeing this more and more. We are using a chemical straitjacket instead of doing things that are just as important to also do, sometimes more.”

Dr. Anderson’s instinct, he said, is that of a “social justice thinker” who is “evening the scales a little bit.” He said that the children he sees with academic problems are essentially “mismatched with their environment” — square pegs chafing the round holes of public education. Because their families can rarely afford behavior-based therapies like tutoring and family counseling, he said, medication becomes the most reliable and pragmatic way to redirect the student toward success.

The entire story is here.

J&J Settles Lawsuit Alleging Injury From Antipsychotic

By Peter Loftus

The Wall Street Journal

Originally published September 10, 2012

Johnson and Johnson agreed to a last-minute settlement of a lawsuit claiming that a boy's use of its antipsychotic drug Risperdal caused abnormal breast growth.

The settlement—whose terms were confidential—averted a civil trial scheduled to begin Monday in which plaintiffs' lawyers intended to summon J&J Chief Executive Alex Gorsky as a witness. Mr. Gorsky previously held leadership roles at the J&J division responsible for marketing Risperdal during the period when the boy's alleged injury occurred.

Robert C. Hilliard, an attorney for the plaintiff, told a judge in the Philadelphia Court of Common Pleas Monday "this case has reached a final resolution." He said the settlement amount was confidential.

The entire story is here.

Creation of a Central Management Plan for Every New Drug Needed to Strengthen FDA's Oversight of Approved Drugs' Safety

National Academies of Sciences
Released May 1, 2012

Although the approval of a new drug is based on evidence that its benefits outweigh its risks, the full range of a medication's effects may not become apparent until a product has been used by a larger, more diverse population over an extended period of time.  Problems associated with the anti-diabetes drug Avandia, pain reliever Vioxx, and cholesterol-reducing drug Crestor illustrate the challenges and underscore the need for a more systematic and transparent process to collect, assess, and act on data about a medication's benefit-risk profile throughout its entire "life cycle" from approval until it is no longer marketed, says a new report by the Institute of Medicine. 

According to recent estimates, nearly half of all Americans take at least one prescription drug daily and many older people use five or more, noted the committee that wrote the report.  The report's recommendations build on the new authorities and tools provided to the U.S. Food and Drug Administration through the Food and Drug Administration Amendments Act of 2007, which increased the agency's capacity to monitor drugs after approval and act if signs of safety problems appear. 

One of the committee's key recommendations is that FDA should create a benefit and risk assessment and management plan for each drug.  This would be a single, comprehensive, publicly available document that serves as a central repository of information for each product from its approval throughout its entire time on the market.  The document should include a description of any safety questions that exist when a drug is approved or that emerge over the course of the product's use, as well as benefit and risk assessments specific to these questions.  It should also include details on regulatory actions taken on the medication, such as restrictions on its use or the decision to require further research, as well as the results of these actions.  Much of this information is already being gathered by FDA, but it is currently scattered across multiple records.  Putting the information into an accessible format in a single document would make FDA's commitment to the life-cycle approach concrete and improve its transparency by giving the public easier access to useful data.

The entire news release is here.

Abbott Settles Marketing Lawsuit

By Michael S. Schmidt and Katie Thomas
The New York Times - Business Day
Originally published May 7, 2012

The pharmaceutical company Abbott Laboratories said on Monday that it had reached an agreement with the federal and nearly all state governments to pay $1.6 billion in connection with its illegal marketing of the anti-seizure drug Depakote.

The settlement comes as the Justice Department and the states have increased scrutiny of the sales and marketing practices of pharmaceutical companies, particularly in cases in which they market drugs for uses that are not approved by the Food and Drug Administration.

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Doctors may prescribe drugs for any purpose, but pharmaceutical companies are prohibited from promoting drugs for conditions that are not approved by the agency.

The entire story is here.