Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo

* surprinzator

Broad Review of FDA Trials Suggests Antidepressants Only Marginally Better than Placebo

Deborah Brauser

Pharmacotherapy for Major Depressive Disorder (MDD)
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August 24, 2010 — A new review of 4 meta-analyses of efficacy trials submitted to the US Food and Drug Administration (FDA) suggests that antidepressants are only "marginally efficacious" compared with placebo and "document profound publication bias that inflates their apparent efficacy."

In addition, when the researchers also analyzed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, "the largest antidepressant effectiveness trial ever conducted," they found that "the effectiveness of antidepressant therapies was probably even lower than the modest one reported...with an apparent progressively increasing dropout rate across each study phase.

"We found that out of the 4041 patients initially started on the SSRI [selective serotonin reuptake inhibitor] citalopram in the STAR*D study, and after 4 trials, only 108 patients had a remission and did not either have a relapse and/or dropped out by the end of 12 months of continuing care," lead study author Ed Pigott, PhD, a psychologist with NeuroAdvantage LLC in Clarksville, Maryland, told Medscape Medical News





* Discernamintul la psihopati

We conclude that psychopaths make the same kind of moral distinctions as healthy individuals when it comes to evaluating the permissibility of an action embedded in a moral dilemma. Consequently, these results support the hypothesis that normal social emotional processing does not appear necessary for making these kinds of moral judgments. Normal emotional processing is likely to be most important in generating an appreciation of these distinctions and in guiding actions (Huebner et al., 2008). Psychopaths know what is right or wrong, but simply don't care. Given that legal distinctions often turn on whether crimes are committed knowingly (e.g., Model Penal Code), these results could have bearing on court decisions concerning the nature of moral knowledge – i.e. instead of strictly focusing on criminal actions carried out knowingly, we should also focus on whether such knowingly immoral and illegal actions are carried out caringly. Equally important, these results may shed light on treatment, pushing clinicians to distinguish between the sources of deficit regarding morally relevant decisions and actions.

eMedicine Article - Dissociative Disorders

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* trecerea la...

Relapse in depression
Relapse in patients with depression is a potential consequence of residual symptoms.
Learn more about relapse in depression

Abstract and Introduction


Background: Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs) on cognitive performance over time.
Methods: In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13) or novel antipsychotics (n = 26) at baseline and at two years after.
Results: Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics.
Conclusions: Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

* statine dupa accident cerebral

Cholesterol Reduction and the Brain–Heart Connection

Steven R. Levine, MD

                                   Are your patients with moderate to severe chronic pain taking other medications?
 These patients may be at risk for drug-drug interactions.
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Abstract and Introduction


A post hoc analysis of SPARCL data provides additional support for the benefits of statin therapy after a stroke or transient ischemic attack, in terms of both brain and cardiac protection.

* adhd la adult

Efficacy of Meta-Cognitive Therapy for Adult ADHD

Mary V. Solanto, Ph.D., David J. Marks, Ph.D., Jeanette Wasserstein, Ph.D., Katherine Mitchell, Psy.D., Howard Abikoff, Ph.D., Jose Ma. J. Alvir, Dr.P.H., and Michele D. Kofman, Ph.D.

Objective: The authors investigated the efficacy of a 12-week manualized meta-cognitive therapy group intervention designed to enhance time management, organization, and planning in adults with attention deficit hyperactivity disorder (ADHD).

Method: Eighty-eight clinically referred adults who met DSM-IV criteria for ADHD according to clinical and structured diagnostic interviews and standardized questionnaires were stratified by ADHD medication use and otherwise randomly assigned to receive meta-cognitive therapy or supportive psychotherapy in a group modality. Meta-cognitive therapy uses cognitive-behavioral principles and methods to impart skills and strategies in time management, organization, and planning and to target depressogenic and anxiogenic cognitions that undermine effective self-management. The supportive therapy condition controlled for nonspecific aspects of treatment by providing support while avoiding discussion of cognitive-behavioral strategies. Therapeutic response was assessed by an independent (blind) evaluator via structured interview before and after treatment as well as by self-report and collateral informant behavioral ratings.

Results: General linear models comparing change from baseline between treatments revealed statistically significant effects for self-report, collateral report, and independent evaluator ratings of DSM-IV inattention symptoms. In dichotomous indices of therapeutic response, a significantly greater proportion of members of the meta-cognitive therapy group demonstrated improvement compared with members of the supportive therapy group. Logistic regression examining group differences in operationally defined response (controlling for baseline ADHD severity) revealed a robust effect of treatment group (odds ratio=5.41; 95% CI=1.77–16.55).

Conclusions: Meta-cognitive therapy yielded significantly greater improvements in dimensional and categorical estimates of severity of ADHD symptoms compared with supportive therapy. These findings support the efficacy of meta-cognitive therapy as a viable psychosocial intervention.

* opioide

An Opioid Deficit in Borderline Personality Disorder: Self-Cutting, Substance Abuse, and Social Dysfunction

Antonia S. New, M.D., and Barbara Stanley, Ph.D.
Borderline personality disorder is far more common than has been previously recognized, with a prevalence rate as high as 5.9% in the general population (1). The disorder has high morbidity and mortality: these patients have higher rates of suicide and poor functioning and utilize more mental health resources than most patients with axis I diagnoses (2). Psychotherapeutic treatments for borderline personality disorder typically show partial efficacy, and while patients may respond to medications in a circumscribed and often transient manner, there are currently no pharmacologic treatments for borderline personality disorder approved by the Food and Drug Administration. Patients are, therefore, left without the benefit of reliable and effective therapies. Furthermore, pharmacotherapeutic and neurobiological research that might inform treatment in borderline personality disorder has made less progress than one would hope, especially considering the seriousness and pervasiveness of the disorder.

The article in the current issue by Prossin and colleagues (3) holds promise for helping to move the field forward. They present evidence that patients with borderline personality disorder suffer from a definitive abnormality in opioid activity. While there has been a great deal of interest in the opioid system in borderline personality disorder (4), until this study, the role of opioids in borderline personality disorder was largely theoretical with little empirical support. The few pieces of evidence—reviewed by Stanley and Siever (4)—include 1) decreased endogenous opioids, especially beta-endorphins and met-enkephalins, in self-injurers with cluster B personality disorders (predominantly borderline personality disorder) compared to individuals without self-injury (5); and 2) a reported association between a µ-opioid gene polymorphism and borderline personality disorder. Prossin and colleagues, however, are the first to measure µ-opioid receptor binding directly in the brains of living patients with borderline personality disorder.

They used a µ-opioid ligand, [11C]carfentanil, to examine binding in the cerebral cortex of patients with borderline personality disorder during induction of neutral and sad sustained emotional states. The participants were female patients with borderline personality disorder and matched healthy comparison subjects. During the neutral state, the patients showed more µ-opioid binding in regions of the prefrontal cortex, in the reward center (accumbens), and in the amygdala, while the comparison subjects showed more µ-opioid binding in the thalamus. µ-Opioid binding in the prefrontal cortex during the neutral mood correlated negatively with neuroticism in borderline personality disorder. During induced sadness, neurotransmission mediated by µ-opioid receptors was greater in the patients than in the comparison subjects. An important feature of the study is that it experimentally manipulated the subjects' emotional state, since opioid ligand binding is likely to be state dependent. The authors interpreted the greater baseline µ-opioid receptor availability in borderline personality disorder as perhaps reflecting a deficit in endogenous circulating opioids. The results also seems to suggest that enhancement of endogenous opioid availability during sad mood is greater in patients with borderline personality disorder than in healthy subjects, which might reflect a compensatory response and is consistent with lower levels of endogenous opioids in self-injurers (5).


How might abnormal opioid activity help to explain the symptoms and etiology of borderline personality disorder? For decades, researchers have theorized that at least one behavior common in borderline personality disorder—self-cutting—relates to abnormalities in opioid activity. It has long been noted that patients with borderline personality disorder report that they engage in self-cutting not as a suicidal act but, rather, as a means to relieve psychic pain. Many patients report that they do not feel physical pain at the moment when they cut themselves; instead, cutting engenders feelings of relief or well-being. One view of cutting in borderline personality disorder is that it represents a method of endogenous opioid generation. In this view, patients learn to cut themselves, thereby releasing opioids, which reward their behavior. This, coupled with evidence that patients with borderline personality disorder who do not cut themselves are less symptomatic than those who do, led to efforts to treat borderline personality disorder with opiate antagonists by eliminating the positive feedback from cutting. While we know of no large-scale randomized, controlled trial, pilot studies on the efficacy of opiate antagonists showed mixed results (reviewed in reference 4) and overall showed that while opiate antagonists may slightly decrease cutting behavior, they do not improve the intrapsychic distress that leads to the cutting (6). This lack of diminished distress is consistent with the model of opioid deficiency.

Thus, a promising way of construing cutting behavior in borderline personality disorder is to consider that these patients may have a preexisting deficit in endogenous opioids. According to this view, patients are self-medicating by cutting themselves, attempting to attenuate severe intrapsychic distress that healthy individuals—without such a deficit—would not be experiencing. This is consistent with the observation that opiate antagonists might decrease cutting behavior by rendering ineffective the patient's attempts to treat his or her pain (thereby decreasing the frequency of cutting) but would not relieve the underlying intrapsychic distress. A deficit in opioids is also consistent with the high rate of opiate abuse in borderline personality disorder, as patients may be compensating for a deficit in endogenous opioids. Not only is there is a high rate of opiate abuse in borderline personality disorder, but there is also a high rate of borderline personality disorder among patients seeking substance abuse treatment; for instance, 44.1% of individuals seeking buprenorphine treatment have borderline personality disorder (7). Clinically, it has been noted that individuals with borderline personality disorder who are taking opiates report feeling euthymic rather than euphoric, while withdrawal is associated with sustained dysphoria.

An opioid-deficit theory of borderline personality disorder might explain far more than the self-injurious behavior of these patients. For example, their extraordinary difficulties in social behavior may also be linked to a preexisting deficit in endogenous opioids. The endogenous opioid system not only regulates pain but also has an important role in social behavior. This system, through µ-opioid receptors, has long been implicated in regulation of emotional and stress responses. Reductions in its function have been associated with attachment behavior deficits and anxiety-like responses in animal models. In many species, the soothing and comforting that infants receive from maternal grooming and touching is mediated through the opioid system (8). In human beings, opioids are involved in normal and pathological emotion regulation (9) in addition to their more traditional role in modulating the sensory and affective dimensions of pain (10). In short, there is reason to think that endogenous opioids facilitate normal social function in healthy individuals.

If the proposed model is accurate, then a deficit in endogenous opioids might go some way toward explaining not only cutting behavior and substance abuse in borderline personality disorder but also the almost ubiquitous social dysfunction observed in this condition. Gunderson has argued for a greater focus on interpersonal dysfunction in understanding borderline personality disorder, stating that the relational style characteristic of the disorder "offers the best discriminators for the diagnosis" of borderline personality disorder (11). Mood shifts and self-destructive behaviors in borderline personality disorder seem to arise specifically in response to interpersonal triggers (12). Furthermore, the domains of intrapsychic pain and interpersonal dysfunction in borderline personality disorder are closely linked.



The findings of Prossin and colleagues have both broad and specific clinical implications. Broadly, they lend support to a model of an opioid deficit in borderline personality disorder that may be "hard wired" (consistent with the high heritability of borderline personality disorder). This view could provide a heuristic model to help patients and clinicians understand the social disruption in borderline personality disorder. The satisfaction that normally accompanies closeness to other people both in early attachment and throughout life may elude patients with borderline personality disorder. If these individuals do not have sufficient endogenous opioids, then the continual craving for relationships and heightened reaction to their loss is understandable. Such a model could provide a better understanding and improve management of disappointment in relationships for patients. It might also destigmatize the disorder; the difficulty in forming a therapeutic alliance, for example, could be reconstrued as the result of an opioid deficit. Furthermore, it provides support for targeting the µ-opioid receptor as a novel molecular target for pharmacotherapy in borderline personality disorder.


Dr. New receives research funding from the Department of Defense, NIMH (as a co-investigator with funding), and the Mental Illness Research and Clinical Center (MIRECC) through the Veterans Administration (pilot funds and salary). Dr. Stanley receives research support from NIMH, the National Institute on Alcohol Abuse and Alcoholism, the Department of Defense, and the American Foundation for Suicide Prevention. Dr. Freedman has reviewed this editorial and found no evidence of influence from these relationships.

Address correspondence and reprint requests to Dr. New, Department of Psychiatry, Mount Sinai School of Medicine, Box 1218, One Gustave Levy Place, New York, NY 10029; (e-mail). Editorial accepted for publication April 2010.


  • Grant BF, Chou SP, Goldstein RB, Huang B, Stinson FS, Saha TD, Smith SM, Dawson DA, Pulay AJ, Pickering RP, Ruan WJ: Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2008; 69:533–545[Medline]
  • Zanarini MC, Frankenburg FR, Khera GS, Bleichmar J: Treatment histories of borderline inpatients. Compr Psychiatry 2001; 42:144–150[CrossRef][Medline]
  • Prossin AR, Love TM, Koeppe RA, Zubieta J-K, Silk KR: Dysregulation of regional endogenous opioid function in borderline personality disorder. Am J Psychiatry 2010; 167:925–933[Abstract/Free Full Text]
  • Stanley B, Siever LJ: The interpersonal dimension of borderline personality disorder: toward a neuropeptide model. Am J Psychiatry 2010; 167:24–39[Abstract/Free Full Text]
  • Stanley B, Sher L, Wilson S, Ekman R, Huang YY, Mann JJ: Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters. J Affect Disord 2010; 124:134–140[CrossRef][Medline]
  • Schmahl C, Meinzer M, Zeuch A, Fichter M, Cebulla M, Kleindienst N, Ludascher P, Steil R, Bohus M: Pain sensitivity is reduced in borderline personality disorder, but not in posttraumatic stress disorder and bulimia nervosa. World J Biol Psychiatry 2010; 11(2, part 2):364–371
  • Sansone RA, Whitecar P, Wiederman MW: The prevalence of borderline personality among buprenorphine patients. Int J Psychiatry Med 2008; 38:217–226[CrossRef][Medline]
  • Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG: Endogenous opioids and social behavior. Neurosci Biobehav Rev 1980; 4:473–487[CrossRef][Medline]
  • Kennedy SE, Koeppe RA, Young EA, Zubieta JK: Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry 2006; 63:1199–1208[Abstract/Free Full Text]
  • Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS: Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 2001; 293:311–315
  • Gunderson JG: Disturbed relationships as a phenotype for borderline personality disorder (commentary). Am J Psychiatry 2007; 164:1637–1640[Free Full Text]
  • Brodsky BS, Groves SA, Oquendo MA, Mann JJ, Stanley B: Interpersonal precipitants and suicide attempts in borderline personality disorder. Suicide Life Threat Behav 2006; 36:313–322[CrossRef]






* pastrati doza 1 an!

Analysis of Antipsychotic Dose Reduction

Hiroyuki Uchida, M.D., Ph.D., Takefumi Suzuki, M.D., Ph.D., Hiroyoshi Takeuchi, M.D., and David C. Mamo, M.D., M.Sc., F.R.C.P.C.

Tokyo, Japan
Toronto, Ontario, Canada
Tokyo, Japan
Toronto, Ontario, Canada

To the Editor: In the June 2010 issue of the Journal, Chuan-Yue Wang, M.D., Ph.D., et al. (1) conducted an open-label randomized controlled trial to examine the effects of reducing the risperidone dose in schizophrenia patients who had completed an acute phase treatment. The authors concluded that maintenance treatment at the initial dose for at least 1 year was safer and more effective in relapse prevention than the reduced dose strategy.

* sindromul de depersonalizare

Depersonalization: A New Look at a Neglected Syndrome

by Mauricio Sierra. New York, Cambridge University Press, 2009, 182pp., $90.00.

Eric Hollander, M.D.

Bronx, N.Y.

Depersonalization is a fascinating phenomenon that challenges assumptions regarding one's existence and identity. Depersonalization is an alteration in the perception or experience of the self, so that one feels detached from, or as an outside observer to one's mental processes or body, as if in a dream, or feeling unreal. In this scholarly book, Sierra pulls together recent research and relates it to 100 years of thinking about this puzzling condition. He also provides a scale in the appendix that serves as a very useful screening tool for depersonalization for clinicians and investigators.

While the book is subtitled A New Look at a Neglected Syndrome, I would suggest that there is quite a lot of interest in this syndrome at the current time. For example, the DSM-5 Work Group on Anxiety, Obsessive-Compulsive Spectrum, and Posttraumatic, and Dissociative Disorders is evaluating whether to group dissociative disorders such as depersonalization disorder within a broader grouping of posttraumatic and anxiety conditions.

The syndrome and its symptoms have been well described since the early 19th century, with extensive case series published in the 1940s and 1950s, and again in another burst of interest in the 1990s and 2000s. However, throughout the years, the clinical presentations have been surprisingly similar with regard to signs and symptoms. Depersonalization disorder is certainly not rare, having a prevalence of about 1% of the population. It begins in the teens, may last for decades, and is remarkably refractory to most treatments.

Depersonalization is described by Sierra as lying along a spectrum of severity, from sporadic and fleeting experiences in youth, which are quite common (up to 70% of college students and 23% of the general population), to symptoms accompanying other comorbid conditions (such as anxiety or obsessive-compulsive disorder), and finally to the severe and disabling pathological depersonalization disorder. Of interest, Daphne Simeon and others have shown that emotional abuse in childhood may predispose to both the nonclinical and pathological forms of depersonalization.

Drug-induced flashbacks and "bad trips" leading to depersonalization disorder have been reported to be precipitated by cannabis, LSD, MDMA (Ecstasy), and ketamine, and are vividly described in the book. These experiences provide clues to the role of terror and loss of control, as well as neurotransmitter mechanisms that play a role in the development of the disorder.

The neurology of the disorder and cultural factors are also well described in the book. Western cultures with their greater emphasis on individualism are surprisingly associated with greater frequency of depersonalization. Of course, pharmacological and psychological approaches to treatment are described, but it is truly remarkable how resistant this disorder remains.

Of greatest interest is Sierra's fronto-limbic, neurobiological model of depersonalization, which posits that depersonalization is a response to deal with extreme anxiety by combining a state of increased alertness with a profound inhibition of the emotional response system by the prefrontal cortex. The prefrontal cortex down-regulates emotional processing of the limbic system, resulting in dampened sympathetic output and reduced emotional experiencing. This response has evolved to cope with life-threatening situations in which the individual does not have control over the situation and the source of danger cannot be localized in space. Inhibition of nonfunctional emotional reactions and the fight-or-flight mechanism, along with increased scanning of survival-relevant information, would be helpful from an evolutionary perspective.

This book provides a wealth of data regarding depersonalization. It attempts with some success to pull together threads from over a century of writings and integrate these observations with recent neurobiological investigations in order to develop a unifying model of the syndrome. It should be an absorbing read not only for scholars working in this field, but also for clinicians who treat patients with depersonalization, as well as keen observers of the human condition.

* identitatea si selful

Personal Identity and Fractured Selves: Perspectives From Philosophy, Ethics, and Neuroscience

edited by Debra J.H. Mathews, Hilary Bok, and Peter V Rabins. Baltimore, Johns Hopkins University Press, 2009, 216pp., $55.00.

Victor I. Reus, M.D.

San Francisco, Calif.

Once Phineas Gage in 1848 recovered from the horrific brain damage that resulted from a three-foot tamping iron being driven through his anterior lobes, his friends were known to remark that "Gage was no longer Gage." A medical curiosity, Gage's story is generally regarded as the first fully detailed example of personality change resulting from brain injury. But what did that statement mean? Should Gage have been considered to be the same person he once was? Or a different entity, having a different sense of self and a different "personhood"? Such questioning about the meaning of personal identity may seem foreign to psychiatric clinicians and a humanistic perspective, but the technical definition of what it means to be a person and to have a personal identity is central to modern philosophical discourse on morality and responsibility. This book is the result of a symposium organized by the Johns Hopkins Berman Institute of Bioethics that brought together three prominent philosophers (Marya Schechtman, Carol Rovane, and John Perry) and two neuroscientists (Michael Gazzaniga and Samuel Barondes) and asked them to consider four case studies in which personal identity was affected by biologic circumstance; the cases chosen included individuals with Alzheimer's disease and frontotemporal dementia, steroid psychosis, and Parkinson's disease treated with deep brain stimulation. The end result, perhaps more surprising to the editors than to the reader, is a relative lack of consensus on the key issues—on who is a person and who is not, on the value of empirical versus conceptual methods, on the importance of conscious versus unconscious motivation, and on the value of physical criteria in assessing psychological capacities. One is reminded of the toast "the Lowells speak only to the Cabots and the Cabots speak only to God"; whether philosophers or neuroscientists are more representative of Lowells or Cabots is a debatable point. The chapter "How Philosophers Think..." by Tumulty is the book's most succinct synopsis of variant approaches to the key questions and their complications, esoteric issues of identity made real through analogies to Coke cans and genetically transformed enemies of James Bond in Die Another Day. There is general agreement in both camps that personal identity can be best characterized by an ability to express a self narrative that endorses the concept of "self" and that strives for consistency, rationality, and intentionality. But at the end of the day, the operational utility of this definition remains a dividing point. The editors suggest that philosophy and neuroscience can inform each other through knowledge that Alzheimer's disease, being irreversible and occurring irrespective of personal choice, has a different effect on personal identity than a psychosis resulting from a personal choice to take steroids. It is unlikely that most psychiatrists would concur, but they may be stimulated by the questions posed.

* intreruperea antidepresivelor

Abrupt Withdrawal of Antidepressant Treatment

Robert Freedman, M.D.

Some studies, while they inform us, nonetheless raise more questions than they answer. In this issue, Baldessarini et al. present provocative information for both clinicians and researchers in their article "Illness Risk Following Rapid Versus Gradual Discontinuation of Antidepressants" (1). The study is not a controlled trial of an intervention, but rather, like much informative clinical research, it is essentially a detailed observation of patients. Patients with mood and anxiety disorders were carefully followed at clinics in Sardinia while they were treated with antidepressants. The study extended from the era of the tricyclic antidepressants to the modern era of selective serotonin reuptake inhibitors. Abrupt discontinuation of medication, usually initiated by patients themselves, was more likely to result in the return of depression within several months, compared to tapering the dosage over several weeks, generally recommended by physicians, which resulted in less likelihood of relapse. All patients included in the study had close to normal mood at the time of medication discontinuation, regardless of who made the decision to stop treatment. Patients whose antidepressants were stopped because of emerging mania were not included in the study. Even when a tapering regimen was used, medications with short half-lives, like paroxetine and venlafaxine, were more likely to produce early relapse than the longer-acting medications, including the tricyclics.

As with any observational study, there are uncertainties. It is possible that the patients who decide to stop medications abruptly have particular characteristics of biology, manifest as cyclothymia and rapid relapse, or histories of trauma or personality disorders or socioeconomic disadvantages that make them more vulnerable to relapse into depression. Although baseline characteristics seem similar between the groups of patients in the study, these factors were not specifically checked. Similarly, the apparent advantage of the tricyclics confounds the differences in drug class with differences both in the decades in which the patients were treated and in the longer half-lives of tricyclics compared to the widely used modern drugs with short half-lives (specifically paroxetine and venlafaxine). There may be factors unique to the setting of the study in Sardinia. For example, Sardinians show signs of relative genetic isolation from other populations (2). Thus, genetic heterogeneity, which might obscure observations of differences in treatment response, is minimized, compared to countries with more diverse populations, such as the United States. Accordingly, there may also be unique aspects to the Sardinian population's biology that lead to rapid relapse that are less likely to occur in more diverse populations.

Despite these uncertainties, it is tempting to ponder the meaning of what was observed. Mood disorders are as interesting for their periodic remission and relapse as they are for their symptoms during the acute illness itself. Although there is much evidence that some of the stigmata of mood disorder persist between episodes, it is a common clinical observation that many patients achieve striking remission only to suffer equally striking relapse (3). An illness with such relapsing-remitting properties is difficult to conceptualize as a biological illness, because a biology that could account for a profound change in mood that lasts several months and then remits is unknown, despite the many efforts that have been made to identify the biology of the "switch process" (4). Perhaps Baldessarini et al. have discovered that the switch process is engaged by an abrupt change in serotonergic or noradrenergic neurotransmission, which could be brought about in some instances by traumatic events or developmental crises, but also by abrupt discontinuation of medication, particularly short-acting medications and particularly in illnesses such as bipolar I disorder, which are most likely to cycle. It is interesting that the effect does not occur immediately during drug withdrawal but rather takes several months to manifest itself. While the complexity of interaction between the pharmacological insult and the biological predisposition to illness cannot be fully modeled in laboratory animals, a laboratory study of the longer-term neurobiological changes that follow abrupt withdrawal of a drug like paroxetine might provide new information on biological mechanisms that might underlie remission and relapse in patients. Reviewers suggested that a similar prospective, randomized study could be conducted in patients, but the authors countered that such a study, which would deliberately expose some patients to an apparent harm, would not be ethical.

Although clinicians rarely advocate abrupt discontinuation of antidepressants in the absence of the emergence of mania, one clinical situation in which it might seem appropriate is pregnancy. If a woman's mood is under control and she is concerned about the effects of paroxetine on her fetus, she or her physician might consider discontinuing her drug quickly. A comparative risk assessment suggests that the risk of antidepressant drug treatment is not negligible, but depression itself, treated or untreated, appears to be a greater risk factor for pregnancy and the fetus (5). Although the Baldessarini et al. study did not note whether any of the patients were pregnant, the authors point out that the findings of the study suggest that abrupt discontinuation might not be a rational decision, even for an asymptomatic woman who is concerned about effects on the fetus, because depression would be more likely to occur later in the pregnancy or in the postpartum period (6).

Accurate record keeping in large populations of patients has led to remarkable insights into the time course of the effects of antidepressants on suicidal behavior in adolescents, effects of antidepressants on diabetes, and now, in this study, the effects of discontinuation pace on relapse (7, 8). Psychiatrists and other physicians are currently being encouraged to transition to the use of electronic medical records. Hopefully, these records can be used constructively to continue long-term observations of the benefits and risks of psychiatric treatments.

* malpractice

Malpractice Threat to Physicians Pervasive, AMA Study Finds

Mark Crane

                                                                     Relapse in depression 
                               Relapse in patients with depression is a potential consequence of residual symptoms.
Learn more about relapse in depression

August 5, 2010 — More than 42% of physicians have been sued for medical malpractice at some point in their careers, and more than 20% were sued at least twice, according to a new American Medical Association (AMA) report.

An average of 95 claims were filed for every 100 physicians — almost 1 per physician — the AMA's Physician Practice Information survey of 5825 physicians, fielded in 2007 and 2008, found.

Despite the pervasive threat of litigation across 42 different specialties surveyed, two thirds of claims are dropped or dismissed, and physicians prevail 90% of the time in cases that go to trial, the study found. Still, the costs to physicians in terms of malpractice premiums and to the entire healthcare system resulting from the practice of defensive medicine are quite high. Average defense costs per claim range from a low of $22,000 among claims that are dropped or dismissed to a high of more than $100,000 for cases that go to trial.

"Even though the vast majority of claims are dropped or decided in favor of physicians, the understandable fear of meritless lawsuits can influence how and where physicians practice, when they retire, and how often they practice wasteful defensive medicine," AMA Immediate Past-President J. James Rohack, MD, told Medscape Medical News. "This litigious climate hurts patients' access to physician care at a time when the nation is working to reduce unnecessary healthcare costs.

"Unfortunately, there are no real surprises in this study for us," said Dr. Rohack, a cardiologist in Temple, Texas. "It reconfirms the need for a solution to our current tort system. If the nation is ever going to control the rise in healthcare costs, we have to eliminate wasteful defensive medicine spending."

Other highlights in the report include:

  • Nearly 61% of physicians aged 55 years and older have been sued.
  • There is wide variation in the effect of liability claims between specialties. The number of claims per 100 physicians was more than 5 times greater for general surgeons and obstetricians/gynecologists than it was for pediatricians and psychiatrists.
  • Before they reach the age of 40 years, more than 50% of obstetricians/gynecologists have already been sued.
  • Ninety percent of general surgeons aged 55 years and older have been sued.

"In any single year, being sued is a rare event. Only 5 percent of physicians had claims filed against them in that time frame. Over the length of a career, however, claims are much more common," the report found.

Using data compiled by the Physician Insurers Association of America, a group of physician-owned or physician-operated liability carriers, the AMA survey found:

  • Sixty-five percent of claims were dropped, dismissed, or withdrawn; 25.7% were settled; 4.5% were decided by alternative dispute mechanism; and 5% were resolved by trial, with the defendant prevailing in 90% of those tried cases.
  • Median indemnity payments were $200,000 for settled claims and $375,000 for tried claims.

Pediatricians and psychiatrists had the lowest incidence of claims. Less than 30% of physicians in either specialty were sued. General surgeons and obstetricians/gynecologists had the highest incidence of claims. Nearly 70% of physicians in those specialties were sued, and more than 200 career claims were filed for every 100 physicians.

Twice as many male physicians had been sued (47.5%) compared with female physicians (23.9%). Male physicians had more than twice as many career claims per 100 physicians, at 111 for men compared with 41 for women. There are several reasons for that disparity. Male physicians are concentrated in the specialties with the highest levels of claims, and female physicians are concentrated in those with the lowest levels. Women also are newer entrants into the medical workforce, so the men had a longer time period, or length of exposure, during which to accumulate claims. Male physicians also worked on average 5 more hours per week than women, resulting in greater exposure. Finally, male physicians were more likely to be practice owners than women.

Practice owners were about 14 percentage points more likely to be sued than employees (47.5% vs 33.4%) because owners incur claims from other physicians and employees of their practices.

The report concludes that the malpractice system "gets it wrong" in terms of compensation for medical errors on both sides of the equation. Citing a 2006 study (N Engl J Med. 2006;354:2024-2033), the report said 27% of claims involving errors were uncompensated. On the flip side, the same percentage of compensated claims did not involve a medical error.

The AMA cites its report to lobby for "proven medical liability reforms to lower health care costs and keep physicians caring for patients," especially caps on awards for pain and suffering. "The findings in this report validate the need for national and state medical liability reform to rein in our out-of-control system where lawsuits are a matter of when, not if, for physicians," said Dr. Rohack.

The AMA favors caps on awards for noneconomic damages. "We know they work," Dr. Rohack said. "Before the reforms in Texas in 2003, obstetricians, neurosurgeons, orthopaedists, and other high-risk specialists were leaving the state. Patients had to travel long distances to see these specialists."

Paul B. Ginsburg, PhD, president of the Center for Studying Health System Change, based in Washington, DC, said the report shows that the threat faced by physicians, particularly in the high-risk specialties, is pervasive.

"We have long known that the medical liability system is a highly ineffective and inefficient mechanism to improve quality," Dr. Ginsburg said. "As the delivery system advances in the area of quality measurement, the crude and poorly targeted liability system seems to be even more inappropriate. In fact, the malpractice system is really obsolete in terms of improving quality and compensating victims."

Dr. Ginsburg argues that the AMA should "aim higher" in its reform efforts. Caps on awards are "a Band-Aid, not true reform. It may reduce the volume of claims and payouts through the system but doesn't improve quality. And the opposition to caps is so dug in that it may be impossible to achieve anyway.

"There are more ambitious proposals, such as granting safe harbors for care delivered in accord with accepted practice guidelines," he added. "Care delivered consistently with those guidelines should be protected." Pilot projects such as special health courts where judges experienced in malpractice cases choose their own experts and decide a case without a jury also are promising, he said.

Dr. Rohack said the AMA also favors these reforms but believes that caps on awards are a proven benefit to physicians.

* depresia rezistenta

Asymmetrical Contribution of Brain Structures to Treatment-Resistant Depression As Illustrated by Effects of Right Subgenual Cingulum Stimulation

Salvador M. Guinjoan, M.D., Ph.D., Helen S. Mayberg, M.D., Elsa Y. Costanzo, M.D., Rodolfo D. Fahrer, M.D., Ph.D., Eduardo Tenca, M.D., Julio Antico, M.D., Daniel Cerquetti, B.Sc., Elisa Smyth, B.A., Ramón C. Leiguarda, M.D. and Charles B. Nemeroff, M.D., Ph.D.

Received January 6, 2010; revised May 7, 2010; accepted May 24, 2010. Dr. Guinjoan is affiliated with the departments of Neurology, Psychiatry, and Neurosurgery at Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) in Buenos Aires; Dr. Mayberg is affiliated with the Departments of Neurology and Psychiatry at Emory University in Atlanta, Georgia; Drs. Costanzo and Fahrer are affiliated with the Department of Psychiatry at FLENI in Buenos Aires; Drs. Tenca and Antico are affiliated with the Department of Neurosurgery at FLENI in Buenos Aires; Drs. Cerquetti, Smyth, and Leiguarda are affiliated with the Department of Neurology at FLENI in Buenos Aires; Dr. Nemeroff is affiliated with the Department of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine in Miami, Florida. Address correspondence to Dr. Salvador M. Guinjoan, FLENI, Cognitive Neurology & Neuropsychiatry, Montañeses 2325 8th floor, C1428AQK Buenos Aires, Argentina; (e-mail).

Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%–20% in women and a slightly lower rate in men. While many patients are successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.

* vit.E si dementa

Dietary Antioxidants and Long-term Risk of Dementia

Devore EE, Grodstein F, van Rooij FJ, et al
Arch Neurol. 2010;67:819-825


Higher dietary consumption of vitamins E and C was previously associated with lower risk for dementia and Alzheimer disease (AD), according to 6-year findings from the Rotterdam Study. The goal of the present population-based, prospective study was to further examine the relationship between intake of major dietary antioxidants and long-term risk of dementia in the same Dutch cohort. The study sample consisted of 5395 participants at least 55 years old who had no dementia and who provided dietary information at study baseline. Mean duration of follow-up was 9.6 years.

Of 465 participants in whom dementia developed during follow-up, 365 were diagnosed with AD. Higher baseline intake of vitamin E was associated with lower long-term risk of dementia (P=.02 for trend), after adjustment for age, education, apolipoprotein E4 genotype, total energy intake, alcohol intake, smoking, body mass index, and use of supplements. Dementia was 25% less likely to develop in participants in the lowest tertile vs the highest tertile of vitamin E intake (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.59-0.95). After multivariate adjustment, dietary intake of vitamin C, beta carotene, and flavonoids were not linked to dementia risk. Findings were similar for AD ris

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