Richard A. Sherer

Following the recommendations of a working group set up to examine the American Psychiatric Association’s (APA) relationship with the pharmaceutical industry, its Board of Trustees has voted to phase out industry-sponsored educational programs and industry-supplied meals at annual meetings and educational symposia.

In a statement, the APA noted that industry-sponsored educational meetings have “invited a concern that the sessions may be biased in favor of the sponsoring company’s medications.”

Nada L. Stotland, MD, MPH, president of the APA, told 

 that the organization’s decision will not affect its other relationships with the industry. “We still receive revenue from [drug companies] for advertising. They will still have exhibits at our meetings. They also sponsor fellowships and research training for minority residents … the board felt that this issue was of greatest concern to most people. We decided to keep education separate from industry support. After the vote, I emailed to our members … I’ve gotten a few complaints and lot of happy responses.”

Stotland said that “the process that resulted in this change actually began over a year ago. Various members have spoken up over the years, voicing concern … about our relationship with the pharmaceutical industry.”

“I announced in March-before I took office-that I would be forming a task force in May,” she continued. Carolyn Robinowitz, MD, said to go ahead.” The task-force members had to face this issue: if we were to contemplate reducing pharmaceutical industry income, what kind of impact would that have on our budget? What would need to be cut? I decided this task force should get all the information and give the board all of their options.”

Pharmaceutical industry support for the APA’s educational meetings has averaged about $1 million per year, Stotland said, or roughly 2% of the organization’s approximately $50 million budget. To make up for the shortfall, Stotland believes the APA must find ways that will streamline its operations.

“Even more important than replacing the revenue is replacing the sessions themselves,” she said. “They often featured very well-known people, and the presentations were put together with a certain kind of sophistication and professionalism. Now we’re going to arrange those [presentations] ourselves, and maybe even charge for them. We might have to raise the registration fee at our annual meeting, which is very low. Of course, we always would be happy to have grants for some projects.”

Stotland continued, “We have over 90 councils and committees … too many to manage. We are greatly paring down the number of councils and committees and learning to do business in new ways. We will have 1 less board meeting this year. And our assembly will take a budget cut as well.”

Stotland emphasized that the board’s action does not reflect general criticism of the pharmaceutical industry. “We have a foundation,” she noted, “that includes a corporate advisory council. They’ve known what we were doing all along. At no point did anyone impugn the industry. We just thought it was better to disconnect the education connection-but not our other relationships.”

Stotland estimates that it will take 2 or 3 years to phase out industry sponsorship of meetings entirely. “This was a big decision for the board,” she said, “because these were very popular sessions. There were some criticisms, but a lot of people go to them, and the meals were a big attraction. Still, the commitment has been made.”

Articles

Following the recommendations of a working group set up to examine the American Psychiatric Association’s (APA) relationship with the pharmaceutical industry, the Board of Trustees has voted to phase out industry-sponsored educational programs and industry-supplied meals at annual meetings and educational symposia.

APA and Pharma-Funded CME Part Ways

Two prominent psychiatrists have agreed to curtail their research activities following revelations about sizable consulting fees from pharmaceutical manufacturers.

Joseph Biederman, MD-who has strenuously denied any wrongdoing-agreed to withdraw from industry-financed programs, including clinical trials currently under way, at Massachusetts General Hospital (MGH). He also agreed to stop participating in speaking engagements and other activities arranged by pharmaceutical companies while allegations against him are under investigation. Dr Biederman had been accused of failing to report more than $1.4 million in outside income to MGH, as required by the hospital’s ethics rules. Dr Biederman notes that the disputed income was earned over 8 years from pharmaceutical and nonpharmaceutical sources. He also notes that Harvard and MGH rules on conflict of interest do not prohibit the earning of outside income. He adds that MGH and Harvard do prohibit investigators from earning more than $20,000 per year since 2004 and $10,000 before then, from a company with which the investigator could have a conflict of interest.

Dr Biederman headed MGH’s Johnson & Johnson (J&J) Center for the Study of Pediatric Psychopathology from 2002 to 2005.  Congressional investigators have released internal e-mails from J&J officials discussing the company’s involvement in the center. In one e-mail, a company official stated, “The rationale of this center is to generate and disseminate data supporting the use of risperidone in this population,” referring to children and adolescents with bipolar disorder.

In a strongly worded letter to the editor of the Wall Street Journal 10 days before his temporary withdrawal was announced, Dr Biederman said, “The center’s goal was to advance science. As a business, J&J naturally sought commercial applications for our work. But any implication that J&J’s interests interfered with the center’s work is wrong.” He added, “Indeed, I have published research critical of J&J compounds.”

In an unrelated case, Charles Nemeroff, MD, resigned as chair of the Department of Psychiatry and Behavioral Sciences at the Emory University School of Medicine. In addition, Dr Nemeroff has agreed to new restrictions on his outside activities. The university announced that it would not submit any applications for grants involving Dr Nemeroff as an investigator or “any other role” for at least 2 years. This is a restriction imposed by Emory, not NIH. As such, if Dr Nemeroff were to relocate to another institution, he would be eligible to apply for NIH research grant funding. Dr Nemeroff will remain “as a professor and will focus on clinical care, teaching, and other academic pursuits,” the university stated.

Dr Nemeroff had earlier agreed to step down as chair of the department pending an investigation of his outside activities. He relinquished the chairmanship after the Atlanta Journal-Constitution reported that Sen Charles Grassley warned the university “of the potential penalties for making false statements or obstructing a congressional examination.”  Grassley’s warning followed the university’s contention that lectures given by Dr Nemeroff for which he was paid by GlaxoSmithKline were “CME-like.” Grassley responded that “neither anyone on my staff, nor any medical expert that they have contacted, has ever heard of the term ‘CME-like.’ It appears to be a new term created at Emory University.”

Update on Conflicts of Interest Allegations

The Dementias: Neuropsychiatric Syndromes of the 21st Century

Medications for Agitation in Dementia: Seeking Efficacy With Safety References

Diagnosing Dementia: Essential for Prognosis, Treatment, and Potential Care

The use of antipsychotics to quiet agitated older adults with dementia has come under increasing fire. After a Canadian study demonstrated an increased risk of adverse events or death with these agents,

 the FDA expanded its earlier warning to physicians.

“This adds to the mounting evidence about potential safety issues surrounding all antipsychotics,” said Kevin Foley, MD, FACP, medical director of the Hauenstein Alzheimer’s Disease and Memory Disorders Program in Grand Rapids, Mich. “It’s like the situation with Vioxx: postmarketing safety data show that there were concerns we weren’t aware of. The data are compelling.

“Those in my field are completely aware of these limitations and are not ignoring the warnings. I’m not sure of the balance of the various specialties of medicine. We need to know how many of these prescriptions are being written by primary care physicians and others. I suspect that most are being prescribed by primary care physicians, certainly for patients in long-term–care facilities.”

In the latest in a series of studies of the risks associated with antipsychotics in patients with dementia, researchers at the University of Toronto and other institutions found that antipsychotic use appears to be widespread.

 “Of residents newly admitted to a nursing home, 17% are started on an antipsychotic drug within 100 days of their admission, and 10% receive only a single antipsychotic prescription,” they wrote.

“In some guidelines, antipsychotic drugs are recommended for short-term use as part of the pharmacologic treatment of delirium,”

 they added, “although there is no randomized controlled trial evidence to support this practice.”

Paula Rochon, MD, MPH, FRCPC, lead author of the Canadian study, told 

 “In another study, we found that one-third of nursing-home residents have a prescription for one of these antipsychotics.”

In a population-based, retrospective cohort study, Rochon and colleagues identified 20,682 matched older adults with dementia living in the community and 20,559 matched individuals living in nursing homes between April 1, 1997, and March 31, 2004. They divided patient groups by living arrangements (community or nursing home residents) as well as by the type of antipsychotic exposure (atypical or conventional) they received. In each residential setting, the patients who received an antipsychotic agent were matched against a group of patients who were not given prescriptions for antipsychotic drugs but who had received at least 1 other medication.

At 30 days, 13.9% of the community-dwelling older adults who received an atypical antipsychotic had experienced a “serious” adverse event, and 2.7% of them had died. “The pattern of serious adverse events was similar among drug exposure groups,” the researchers noted, “but events were more frequent among individuals who received a conventional antipsychotic drug.

“Individuals in the conventional antipsychotic therapy group were 3.8 times more likely to have experienced any serious event at 30 days’ follow-up than those in the control group. Those in the atypical antipsychotic therapy group were 3.2 times more likely to have experienced any serious event leading to a hospital visit or death during the 30 days of follow-up.”

In the nursing home group, 9.4% of the patients who received an atypical antipsychotic drug had experienced a serious event by the 30-day evaluation, and 5.2% had died within 30 days of receiving a prescription for an atypical antipsychotic drug. As with the community group, serious adverse events were common among patients who received conventional antipsychotic medications.

“Relative to nursing home residents in the control group, individuals in the conventional antipsychotic therapy group were 2.4 times more likely to experience a serious adverse event leading to an acute care hospital admission or death. Those in the atypical antipsychotic group were 1.9 times more likely to experience a serious adverse event during 30 days of follow-up.”

“We have done quite a number of studies in this area,” Rochon said in an interview. “We’ve looked at parkinsonism, stroke issues, and death. We did one of the first studies to look at the evidence for these drugs. What was important about the current study was that it tried to put together things that are often somewhat compartmentalized. We felt it was important to know about the whole spectrum of side effects so clinicians can weigh the risks and the benefits. By using observational data for a large group of people who are old and frail, we are able to see the real-world impact of these therapies, which is somewhat different from a clinical trials situation.”

After publication of the latest study, the FDA announced that it is requesting manufacturers of conventional antipsychotics to add a “black box” warning to their labels similar to the one imposed on atypical antipsychotics in 2005. In an alert for health care professionals, the agency said, the “FDA is notifying health care professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis.” It added, “antipsychotics are not indicated for the treatment of dementia-related psychosis.”

In a conference call for reporters, Tom Laughren, MD, director of the FDA’s Division of Psychiatry Products in the Center for Drug Evaluation and Research, said, “For the conventional antipsychotic drugs, this will involve entirely new language. For the atypical drug, this will involve a slight revision of a boxed warning that was already implemented in 2005. Now the boxed warning will say that elderly patients with dementia-related psychosis who are treated with antipsychotic drugs have an increased risk of death.” He added, “It’s important to emphasize that this is not a contraindication. Clinicians still have the option of using these drugs to treat this aspect of dementia at their discretion. However, [these drugs] are not approved for this indication. And we do want clinicians to be aware of the risks in using drugs in this population if they choose to use them.”

Howard Fillit, MD, executive director of the Alzheimer’s Drug Discovery Foundation, said he believes that antipsychotics are an important tool in the clinician’s arsenal but primarily as a last resort.

“I do think antipsychotics can be overused in patients with dementia,” he said in an interview. “The first approach to treatment should be a very informed and disciplined effort at behavioral management, including understanding the triggers for aberrant behaviors, the environment, and any drugs that the patient might be taking that might be increasing his or her confusion. I think there’s a clear approach to the evaluation and management of behavioral disorders. Once all the potentially manageable or treatable causes have been ruled in or out or addressed, we sometimes are left, as physicians treating patients and their families, between a rock and a hard place.”

Rochon concurs. “Our take-away message is the idea that when you’re prescribing a drug therapy, it’s important to know about the spectrum of adverse effects. We’re hoping to give you the information you need when weighing the risks and benefits,” she said.

				1. Rochon PA, Normand SL, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008; 168:
1090-1096.
				2. Bronskill SE, Anderson GM, Sykora K, et al. Neuroleptic drug therapy in older adults newly admitted to nursing homes: incidence, dose and specialist contact. J Am Geriatr Soc. 2004;52:749-755.
				3. American Psychiatric Association. Practice guidelines for the treatment of patients with delirium. Am J Psychiatry. 1999;156(suppl):1-20.
				4. Rochon PA, Stukel TA, Bronskill SE, et al. Variation in nursing home antipsychotic prescribing rates. Arch Intern Med. 2007;167:676-683.


The use of antipsychotics to quiet agitated older adults with dementia has come under increasing fire. After a Canadian study demonstrated an increased risk of adverse events or death with these agents,1 the FDA expanded its earlier warning to physicians.

Antipsychotics in Dementia: Evidence of Risk Mounts

Success with new approaches to the psychotherapeutic treatment of borderline personality disorder (BPD) and other 

 personality disorders has been reported in several studies recently, raising hopes that an intractable set of illnesses may not be as hopeless as once thought.

“Too many therapists still feel that borderline personality disorder is untreatable and is a lifelong drain on the energy of the therapist, the psychopharmacologist, and the entire mental health system," wrote Kenneth R. Silk, MD, in an editorial in the April 2008 issue of the 

 In light of recent studies, he added, “the idea that these patients never change or improve needs revision.”

“There are a number of new treatments for borderline personality disorder. It’s clear that some of those can be helpful,” said Robert J. Gregory, MD. “It used to be that once borderline personality disorder was diagnosed, the patient was expected never to recover. Recent well-controlled studies are not bearing that out. We now see it as one of the better disorders to get. People actually do recover from it. It's a sea change in our thinking, which is gradually permeating to the mental health community.”

Silk’s editorial accompanied a study of Systems Training for Emotional Predictability and Problem Solving (STEPPS).

 A team from the University of Iowa department of psychiatry headed by Nancee Blum, MSW, found that “subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective, cognitive, interpersonal, and impulsive domains, as well as improvements in impulsivity, negative affectivity, mood, and global functioning. These differences yielded moderate to large effect sizes. There was no difference between groups for suicide attempts, self-harm acts, or hospitalizations.” Significantly, “fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up.”

In his editorial, Silk, a professor of psychiatry in the University of Michigan Health System, wrote that “what is intriguing about the study by Blum and coworkers is that this nonpharmacologic intervention . . . is essentially an augmentation of or adjunct to treatment that is already occurring for the borderline personality disorder patient. It combines 20 weekly sessions of cognitive behavior and skills training elements with a systems approach that involves family members, significant others, and health care professionals with whom the patient interacts regularly.”

He added, “it would appear sensible to use STEPPS as an adjunct, particularly to an intervention in which effectiveness is limited in areas where STEPPS has shown to have beneficial impact. Perhaps as we study the impact of specific . . . psychotherapeutic interventions, we may be able to combine or sequence various interventions to get a greater degree of the effectiveness of psychotherapy.”

A different approach to treatment of personality disorder is found in a study in 

The Journal of Nervous and Mental Disease

 Lead author Allan Abbass and his colleagues examined the efficacy of intensive short-term dynamic psychotherapy (ISTDP). “The emphasis of ISTDP is to rapidly help the patient experience unconscious emotions that are leading to unconscious anxiety, symptom disturbances, and various defenses,” the authors wrote. The main technical interventions are to encourage the awareness and experience of feelings while clarifying and challenging defenses in collaboration with the patient.”

In the study, “those treated with ISTDP had an average of 27.7 . . . treatment sessions and, during this time, mean ratings moved into the normal range for both [brief symptom inventory] and [inventory of interpersonal problems]. . . . They significantly outperformed controls on each measure.”

“The ISTDP treatment group made functional gains whereas controls did not. Work hours more than doubled in the ISTDP group and all were employed by the end of therapy. In
the control condition, 1 worker became unemployed. ISTDP-treated participants stopped 69% of all medications.”

Control patients, who had monthly meetings with the site coordinator that were designed as supportive psychiatric follow-ups, experienced “small but significant patient- and clinician-rated symptom reduction,” the authors noted. “These sessions were designed to mimic standard psychiatric care, which should offer some benefit to patients often referred in crisis,” they said.

In phase 2 of the study, the control group was given ISTDP. “Once the control group was provided ISTDP, they made similar gains” to those experienced by the primary subjects, the authors wrote.

“ISTDP” is difficult to implement because the challenge has to be done at exactly the right timing so the patient doesn’t feel attacked by the therapist,” Gregory told 

. “Some patients can benefit from it very dramatically. The patients in this study made marked gains in social and occupational functioning. All the patients were working full-time at the 2-year follow-up.

The patients in the study “only had about 26 sessions, which is not a very long time for personality disorders,” Gregory noted. It is very impressive, he said, that such good results were obtained after short-term psychotherapy. “I would look at this as a preliminary study with very promising potential,” he added.

Gregory, associate professor of psychiatry and behavioral sciences at SUNY Upstate Medical University, Syracuse, NY, is the lead author of a recent controlled study of psychodynamic psychotherapy for combined BPD and alcohol abuse that was published in the journal 

Psychotherapy: Theory, Research, Practice, Training

Gregory and his team developed a manual-based protocol for a psychodynamic treatment they called dynamic deconstructive psychotherapy (DDP), which “was developed for particularly challenging cases of BPD, such as those with co-occurring substance use disorders or antisocial personality disorder. . . . DDP aims to activate specific neurocognitive func- tions that are impaired. A major focus is to foster verbalization of affects and elaboration of recent interpersonal experiences into simple narratives so that patients can begin to link their affective experiences to their verbal/ symbolic attribution capacities.

Thirty patients were involved in the study, randomized equally between DDP and community-based treatment programs (treatment as usual, or TAU). They were evaluated for 3 primary outcome measures-parasuicide, alcohol misuse, and institutional care. At 12 months, the proportion of DDP participants reporting parasuicide behavior declined from 73% to 30%; those with alcohol misuse declined from 67% to 30%; and those in institutional care declined from 67% to 10%. During that period, the patients receiving TAU who reported parasuicide behavior declined from 47% to 33%; those with alcohol misuse declined from 67% to 44%; and those in institutional care declined from 67% to 22%.

“DDP may be a particularly cost-effective treatment alternative,” the authors wrote. “In addition to producing clinically meaningful benefits, it was less time-intensive than community care and . . . other manual-based treatments of BPD, it contributed to a marked decrease in institutional care over time, and it was associated with decreased prescriptions for psychotropic medications.”

They concluded, “the results of this study support the need for further research on DDP, including long-term outcomes, mechanisms of action, and efficacy in comparison to other manual-based treatments.”

As Silk wrote in his editorial, “The greater the number of available effective interventions, the better the chance that a patient may be able to improve to a degree where [he or] she feels that life is once again, if it ever was, worth living. Then we will have more evidence to erase the myth that borderline personality disorder is untreatable and that the diagnosis relegates the patient to a life of helplessness and hopelessness.”



1. Silk KR. Augmenting psychotherapy for borderline personality disorder: the STEPPS program. 

2008;165:413-415.
2. Blum N, St John D, Pfohl B, et al. Systems Training for Emotional Predictability and Problem Solving (STEPPS) for outpatients with borderline personality disorder: a randomized controlled trial and 1-year follow-up. 

 2008;165:468-478.
3. Abbass A, Sheldon A, Gyra J, Kalpin A. Intensive short-term dynamic psychotherapy for DSM-IV personality disorders: a randomized controlled trial.

2008;196:211-216.
4. Gregory RJ, Chlebowski S, Kang D, et al. A controlled trial of psychodynamic psychotherapy for co-occurring borderline personality disorder and alcohol use disorder. 

Success with new approaches to the psychotherapeutic treatment of borderline personality disorder (BPD) and other DSM-IV personality disorders has been reported in several studies recently, raising hopes that an intractable set of illnesses may not be as hopeless as once thought.

Personality Disorder: “Untreatable” Myth Is Challenged

Once his colleagues began to recover from the shock, the death of Dr Wayne S. Fenton triggered a discussion in the professional and lay press about the risks of violence to mental health professionals posed by mentally ill patients.Fenton was found unconscious and bleeding in his office in Bethesda, Md, on Sunday, September 3, 2006. He had been beaten severely around the head and died at the scene.

A 19-year-old man, Vitali A. Davydov-his name was published following his arrest-was found nearby with blood on his hands and clothing. Fenton had met with Davydov for the first time the day before, on a referral from a colleague. On Sunday morning, Davydov's father asked Fenton to meet with his son again because the young man was refusing to take his medications.

According to news accounts, the charging document presented in court says that Davydov "elected to make a statement of admission to the crime" after being informed of his rights. Davydov was indicted for the killing on October 26. The charging document also says that Davydov was being treated for schizophrenia and bipolar disorder.

Fenton was director of the Division of Adult Translational Research and associate director for clinical affairs at the National Institute of Mental Health. According to a statement from NIMH, he "authored textbook chapters and more than 50 scientific papers on [the] diagnosis, treatment, outcome, and service delivery for schizophrenia. He also served as Deputy Editor of Schizophrenia Bulletin and served as a consultant to the Department of Justice, Civil Rights Division. He was active in the National Alliance for the Mentally Ill, serving on the Scientific Council of this advocacy organization."

In addition, he was NIMH's liaison to the American Psychiatric Association (APA) and the World Psychiatric Association and was involved in the development of the agenda for the forthcoming DSM-V. Fenton also maintained a private practice in Bethesda and had a reputation for working with extremely difficult patients.

 headlined a story, "Devotion to Most Severe Cases Raises Risk of Personal Danger." The article began, "Wayne Fenton knew better than most about the risk of treating people with severe mental illness," which drew an immediate response from Liz Spikol, managing editor of the 

, who writes a blog about mental illness.

"This is entirely predictable spin, but it's misleading. The fact is, the vast majority of violent crimes are NOT committed by a person with mental illness," she wrote, citing a passage in an August 2005 commentary by Leon Eisenberg, MD, published in 

: "In the public mind, violence is associated with mental illness. Yes, there is a strong association, but . . . persons who are seriously mentally ill are far more likely to be the victims of violence than its initiators."The Post article, quoting Fuller Torrey, MD, said that "each year, people with serious mental illness commit about 750 murders, or five percent of the homicides, in the United States."

But the risks of treating the mentally ill are measurably greater than the risks facing other physicians or the American workforce as a whole. Times Online, a Web site combining reports from 

, reported that "the rate of [being a victim of] non-fatal, job-related violent crime is put at 12.6 per 1000 workers across all occupations in a survey by the US Department of Justice. Among doctors, the rate is 16.2 per 1000. For psychiatrists and mental health professionals, the rate is 68.2 per 1000."

Commenting on the Fenton case, the writer added, "Dr Fenton, 53, clearly had not foreseen that he was at serious risk. And if he couldn't predict it, who can?"

Paul Jay Fink, MD, past president of the APA and a consultant on youth violence and youth murder working with the city of Philadelphia, echoed the same thought in an interview with 

. "Can we actually determine who's going to be violent? We know that patients with untreated schizophrenia have more of a tendency toward violence, especially if they have been using alcohol. We know there are parameters to determine the possible level of dangerousness. Can we ever be 100% accurate? The answer is no."

Fink believes that a psychiatrist, especially one working with unstable patients, has an obligation to learn something about referrals if he or she can.	

"When you have somebody who is dangerous and you don't know them and they don't know you, you need to be careful," he said. "Any little insult can fire up a paranoid patient, and that's a danger. The first thing a psychiatrist should learn is that he should get some information when he does the consultation, so he can get some sense of the presence of danger. You can get a message on your answering machine with no information and end up walking into a patient's gun, so to speak.

"Patients are impulsive," Fink added. "They can react negatively to a remark that you didn't think was terrible."

Inexperience-not a factor in the Fenton case-often leads physicians into difficulty, especially in dealing with mentally ill patients. Fink recalled an example from his own past.

"The uninitiated sometimes make big mistakes and say things they shouldn't say. I did once, 50 years ago, when I was a resident: I was in the residents' area and heard a noise in the day room. I went in and saw a patient of mine screaming and acting very psychotic. He was surrounded by 30 or 40 staff and other patients who were making things worse.

"I walked into the circle, took the patient by the hand, walked him across a lawn and up 2 flights of stairs. I got him into the locked men's ward, and I said 'I'm going to have to take away your ground privileges.' He picked up a water fountain-pulled out the pipes-and threw it through the nurses' station window. I thought, 'That was stupid. It could have been me.'"

Fink's personal experience reflects the findings of researchers of violence against physicians. David Fink, MD, surveyed psychiatric residents at several institutions in Pennsylvania and found that 41% said they had been assaulted and 48% had been threatened during their training. In an essay included in the APA's clinical practice publication Patient Violence and the Clinician, he noted that "Available studies confirm that a substantial percentage, approximately 40 percent, of psychiatric residents will be assaulted at least once during the course of a 4-year residence. . . . Violence against residents cannot be considered as an occasional and acceptable risk of training."

Citing an earlier study, David Fink quoted S. I. Hallack as pointing out a possible reason for the increased risks during residencies: "Psychiatric training programs traditionally place their least experienced doctors in the most difficult treatment situations."

The effort to predict which patients may present a threat is still in its infancy. A study reported in BMC Psychiatry by Abderhalden and colleagues

 noted that the BrØset Violence Checklist has been effective when used with patients in the hospital:"The [checklist] assesses the presence of six observable patient behaviors namely whether the patient is confused, irritable, boisterous, verbally threatening, physically threatening, and attacking objects. The reported discriminatory ability is good with a correct prediction rate around 85%."

Paul Jay Fink suggested that practitioners dealing with unstable or unknown patients might improve their safety by redesigning their offices. "Place your chair closest to the door so you don't paint yourself into a corner. . . . There are times when you may . . . have to leave the door of the office open so that you have vocal access to somebody who will hear you. But that's when you know a patient is threatening.

"Most offices are not organized in the way I'm talking about," he added. "I don't have a single schizophrenia patient in my practice. I'm an analyst; I see patients on the couch. If I had Fenton's practice, which was almost all schizophrenia, I might have a panic button. If I thought a patient was extremely dangerous, I might ask a family member or a colleague to sit in with me. But you can't do that frequently. You've got to know the customer."

 Eichelman BS, Hartwig AC, eds. Patient Violence and the Clinician. Washington, DC: American Psychiatric Press; 1995.


 Abderhalden C, Needham I, Dassen T, et al. Predicting inpatient violence using an extended version of the Brøset-Violence-Checklist: instrument development and clinical application. BMC Psychiatry. 2006;6:17.

Once his colleagues began to recover from the shock, the death of Dr Wayne S. Fenton triggered a discussion in the professional and lay press about the risks of violence to mental health professionals posed by mentally ill patients. Fenton was found unconscious and bleeding in his office in Bethesda, Md, on Sunday, September 3, 2006. He had been beaten severely around the head and died at the scene.

Violence Against Mental Health Professionals: Fenton Death Highlights Concerns

A new study comparing the benefits of second-generation antipsychotics (SGAs) with their older counterparts in patients with schizophrenia has yielded a surprising result. The study, funded by the UK National Health Service, found that the overall differences between first- and second-generation antipsychotics "did not reach statistical significance."

Appearing in the October 2006 issue of Archives of General Psychiatry, the findings from the project called the Cost Utility of the Latest Antipsychotics in Schizophrenia Study (CUtLASS) surprised the research team that reported them.

"If the investigators themselves had any bias or previous expectations, it was in favor of SGAs; we were surprised to refute that hypothesis," they wrote. "The results of this pragmatic randomized trial refute the hypothesis that the use of SGAs is superior to the use of FGAs [first-generation antipsychotics] in terms of quality of life at 1 year," they wrote, adding, "The confidence intervals for this effect in the opposite direction were wide, including the possibility of a small benefit for SGAs, but much smaller than we had hypothesized."

"What this study and the CATIE [Clinical Antipsychotic Trials of Intervention Effectiveness] study suggest is that FGAs, which are much cheaper than the SGAs, are a reasonable choice," said Anthony F. Lehman, MD, chair of the department of psychiatry at the University of Maryland School of Medicine. "In the recent era, one felt like he was giving inferior care if he prescribed an older drug."

But Lehman noted that treatment for schizophrenia is not a one-size-fits-all proposition. "Taking it from the data to actual practice, what we have to remember is that no one is average. All of these studies tell us about average effects. On average, the agents yield about the same results. That doesn't really predict for an individual patient what's going to happen.

"In clinical practice, you select a drug based on a variety of factors for the needs of the patients: the history of side effects, the prior response to a particular agent, the preference the patient has. You can even add cost into this. You make an informed choice for the patient [of] the best drug to at least start with. What these studies show is that the advantages of one or the other drug may be less than we might have thought they were."

In recent years, second-generation or atypical antipsychotics have attracted a following based in part on concerns that patients receiving the older, or first-generation, drugs "have had a suboptimal outcome, with symptomatic relapses and disabling adverse effects, particularly sedation and extrapyramidal symptoms [EPS]," according to the CUtLASS researchers.

Peter B. Jones, MD, PhD, of the department of psychiatry at the University of Cambridge, the lead researcher on the study, summarized the attitude of clinicians as "beguiled" by the appeal of atypicals.

The UK study involved 227 persons aged 18 to 64 with DSM-IV schizophrenia and related disorders whose psychiatrists had elected to change their treatment because of inadequate clinical response or intolerance of their current medication. They were randomized into 2 groups, one receiving an older antipsychotic and the other an SGA. The patients' own psychiatrists selected one of the agents designated for the appropriate treatment group.

FGAs in the study were chlorpromazine hydrochloride (Thorazine), flupenthixol (Fluanxol), haloperidol (Haldol), loxapine (Loxitane), methotrimeprazine (Nozinan), sulpiride (Dolmatil, Sulpitil), trifluoperazine hydrochloride (Stelazine), zuclopenthixol (Clopixol), and the depot preparations of fluphenazine (Prolixin, others), flupentixol (Depixol), haloperidol, pipotiazine (Piportil), and zuclopenthixol. Two other drugs, thioridazine hydrochloride and droperidol, had been included in the trial protocol but were dropped because they were withdrawn from licensed use.

SGAs used in the trial were risperidone (Risperdol), olanzapine (Zyprexa), amisulpride (Solian), zotepine (Zoleptil), and quetiapine (Seroquel). Another atypical, ziprasidone, was not included because it has not been licensed in England. Not all of the drugs used in the trial are available in the United States.

The patients were evaluated using the Quality of Life Scale (QLS) at baseline and again at 12, 26, and 52 weeks. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS); Calgary Depression Scale; the Drug Attitude Inventory and a 7-point drug adherence scale; Global Assessment of Functioning Scale; and several adverse effects scales to monitor for negative reactions.

In the end, "participants in the FGA arm tended to have greater improvements in QLS and symptom measures than those in the SGA arm, suggesting that the failure to find an advantage for SGAs was not due to the sample simply being too small. We emphasize that we do not present a null result; the hypothesis that SGAs are superior was clearly rejected," the researchers wrote.

Manufacturers of the newer drugs were quick to respond to the study. "I see at least design flaws with the study," said James Minnick, a spokesman for AstraZeneca, which makes the SGA Seroquel (quetiapine). "Patients were randomized to either first-generation or second-generation treatment, but the choice of medication wasn't random. Patients weren't blinded to what they were taking. The other point might be that every medication is different, and by lumping all second-generation drugs together and inferring they are the same, their unique attributes are undermined."

But Robert W. Baker, MD, group director of global product safety in therapeutic areas for Eli Lilly and Company, put a more positive face on the results. "It's valuable and interesting information for clinicians," he said. "It is useful if they . . . [learn] from this study and the vast existing literature on antipsychotics. It reinforces the notion that because individual drugs and patients differ from each other, clinicians can help their patients best if they are well informed and aggressively pursue the best choice."Eli Lilly's Zyprexa (olanzapine) was one of the SGAs included in the study and fared reasonably well in terms of acceptance. At the end of the study, 74% of the SGA patients for whom olanzapine had been prescribed were still taking the drug.

While quality of care was a principal focus of the study, the cost of care was clearly the driving force. "The key question was whether the additional acquisition costs of SGAs over FGAs would be offset by improvements in health-related quality of life or savings in the use of other health and social care services in people with schizophrenia for whom a change in drug treatment was being considered for clinical reasons, most commonly suboptimal efficacy or adverse effects," the researchers wrote.	

In their findings, however, they note that although the mean costs for patients in the FGA arm of the study were lower, the "major cost in both groups was psychiatric hospital inpatient admissions: 93.2% of total costs in the FGA arm and 81.5% in the SGA arm. Antipsychotic drug costs accounted for a small proportion of total costs (2.1% in the FGA arm and 3.8% in the SGA arm).

"This calls into question how valuable it is to think of these drugs as a class as opposed to trying to think about the right treatment for each individual," Baker noted. "Some people may take a headline, just choose only cost, but [this applies] only the farther away you are from patients and clinical realities. This signals how much you have to individualize the choices."

Lehman also worries that policy makers will use cost considerations as a way of restricting treatment options. "When we go for treatment, we don't want our choices to be constrained by costs. It would be a shame for someone not to have access to a treatment that might be better for them because of a policy decision only to have the cheaper drugs or to have to fail with a cheaper drug first. That's true for other medical conditions, as well. We are balancing a range of choices with cost.

"Instead we should look at prescribing practices that tend to drive costs up more, such as inappropriate prescribing for other indications. This is not always done by mental health practitioners but by family physicians and others who are not as familiar with the literature. We see people using multiple drugs in the same class. Why do you need to take 3 antipsychotics?

"There are lots of ways of reducing costs without restricting the nature of drugs available. That's just a blunt instrument, although policy often uses blunt instruments."  

A new study comparing the benefits of second-generation antipsychotics (SGAs) with their older counterparts in patients with schizophrenia has yielded a surprising result. The study, funded by the UK National Health Service, found that the overall differences between first- and second-generation antipsychotics did not reach statistical significance.