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 In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. 



Recent studies demonstrate an increased teratogenic risk for valproate and a probable increased risk for phenobarbital. Carbamazepine and lamotrigine appear relatively safe; however, results are inconclusive concerning a specific risk for cleft lip/palate for both drugs as well as a dose-dependent effect for malformations associated with lamotrigine. Data regarding teratogenic risks for other antiepileptic drugs are inadequate. Additional studies are needed to delineate further the risks for all antiepileptic drugs and determine the underlying mechanisms.










NEW YORK — January 8, 2009 — There is a large increased long-term risk of mortality in patients with Alzheimer’s disease (AD) who are prescribed antipsychotic medication, according to the long-term follow-up results of the Dementia Antipsychotic Withdrawal Trial (DART-AD) published early online and in the February edition of The Lancet Neurology.


While there is evidence of modest short term benefits of antipsychotic treatment for the neuropsychiatric symptoms of AD, there is also clear evidence of an increase in adverse effects. However, all the data regarding mortality so far relate to short term follow-up of 12 weeks or less.


Clive Ballard, MD, Wolfson Centre for Age-Related Diseases, King’s College London, London, United Kingdom, and colleagues have provided the first long-term follow-up data for AD patients given antipsychotic drugs.


Between 2001 and 2004, patients with AD aged 67 to 100 years who resided in facilities in 4 UK areas were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluorperazine, or risperidone) for 12 months or to switch their medication to an oral placebo.


The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrolment of the last participant (range 24-54 months). Causes of death were obtained from death certificates.


In total, 165 patients were randomised and of these, 128 started treatment — 64 on antipsychotics, 64 on placebo. At 12 months, there was 70% survival in the antipsychotic group compared with 77% in placebo.


However, longer term follow-up revealed bigger differences in survival. At 2 years, survival was 46% in the antipsychotic group and 71% in the placebo group, and at 36 months the difference was even greater: 30% antipsychotic versus 59% placebo. Overall, across the whole study period, the risk of death was 42% lower in the placebo group than in the antipsychotic group.


“Our data add further serious safety concerns about the long-term use of antipsychotics in this population, and clinicians should certainly try to replace antipsychotics with safer management approaches,” the authors wrote.


“Several studies have shown that psychological management can replace antipsychotic therapy without any appreciable worsening of neuropsychiatric symptoms; and although cholinesterase inhibitors do not seem to be an effective short-term pharmacological treatment for agitation, there is evidence that memantine or antidepressants such as citalopram might be safer and effective alternatives for some neuropsychiatric symptoms.”


“Our opinion is that there is still an important but limited place for atypical antipsychotics in the treatment of severe neuropsychiatric manifestations, particularly aggression, of AD,” they continued. “However, the accumulating safety concerns, including the substantial increase in long-term mortality, emphasise the urgent need to put an end to unnecessary and prolonged prescribing.”


SOURCE: The Lancet Neurology


Most Babies With Uncomplicated Febrile Seizures Can Avoid Lumbar Puncture

BOSTON — January 6, 2008 — Researchers have found that it is probably not necessary to perform a lumbar puncture in well-appearing children who have had a simple febrile seizure. The findings are published in the January issue of Pediatrics.


Current American Academy of Pediatrics recommendations, issued in 1996, call on physicians to consider doing a lumbar puncture in children aged 12 to 18 months with a first simple febrile seizure and to ‘strongly’ consider lumbar puncture for infants aged 6 to 12 months.


But when Amir Kimia, MD, Division of Emergency Medicine, Children’s Hospital Boston, Boston, Massachusetts, and colleagues reviewed the medical charts of 704 babies seen at Children’s emergency department for a first simple febrile seizure between October 1995 and October 2006, they found no cases of bacterial meningitis in either age group.


Of the 704 babies, 271 (38%) underwent lumbar puncture. Of these, 10 babies (3.8%) were found to have an elevated white-blood-cell count in their cerebrospinal fluid, but no pathogen was identified in cerebrospinal fluid cultures, and no patient was diagnosed as having bacterial meningitis.


This is the first large-scale study to focus specifically on babies aged 6 to 18 months. The findings are consistent with those of previous small-scale studies in this young age group and studies that included children up to age 6.


However, the researchers caution that their findings don’t necessarily extend to patients with complex febrile seizures, patients with concerning symptoms or signs, or patients who have an underlying illness.


“Lumbar puncture should be considered based on clinical presentation, rather than being done routinely,” says Dr. Kimia. “If a child appears very ill, is lethargic, fussy, non-responsive, has neurologic symptoms, or has certain clinical signs, lumbar puncture should be considered no matter how old the child is.”


SOURCE: Children’s Hospital Boston



Deep Brain Stimulation for Patients With Advanced Parkinson Disease Provides Benefits




CHICAGO — January 6, 2009 — Patients with advanced Parkinson disease (PD) who received deep brain stimulation treatment had more improvement in movement skills and quality of life after 6 months than patients who received other medical therapy, but also had a higher risk of a serious adverse events, according to a study in the January 7 issue of the Journal of the American Medical Association.


Frances M. Weaver, PhD, Hines VA Hospital, Hines, Illinois, and colleagues conducted a randomised trial to compare the benefits and risks of deep brain stimulation with those of best medical therapy for patients of a wide age range with PD.


A total of 255 patients with PD were enrolled; 25% of whom were aged 70 years or older. The participants were randomised to receive bilateral deep brain stimulation with leads of the stimulation device implanted in the following locations of the brain: subthalamic nucleus (n = 60) or globus pallidus (n = 61); or received best medical therapy (n = 134), which included management by movement disorder neurologists, who monitored medication use, and nonpharmacological therapy.


The researchers found that at 6 months, deep brain stimulation patients gained an average of 4.6 hours per day of “on” time without troubling dyskinesia, while the average change for the best medical therapy group was 0 hours.


Motor function improved significantly with deep brain stimulation compared with best medical therapy, with 71% of deep brain stimulation patients versus 32% of best medical therapy patients experiencing clinically meaningful motor function improvements at 6 months, while 3% of deep brain stimulation patients and 21% of best medical therapy patients had clinically worsening scores.


Compared with patients in the best medical therapy group, patients in the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores. Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation versus medical therapy.


The overall risk of experiencing a serious adverse event was 3.8 times higher in deep brain stimulation patients than in best medical therapy patients. A total of 49 deep brain stimulation patients (40%) experienced 82 serious adverse events. Of the patients in the best medical therapy group, 15 (11%) experienced 19 serious adverse events. The most common serious adverse event was surgical site infection, with other serious adverse events including nervous system disorders, psychiatric disorders, device-related complications, and cardiac disorders.


“The clinical significance of the adverse events and minor neurocognitive changes observed in patients in the deep brain stimulation group and, more importantly, whether patients who undergo deep brain stimulation view improvement in motor function and quality of life as outweighing adverse events, remain to be explored,” the authors wrote.


“More detailed analyses of adverse events and neurocognitive functioning following the conclusion of phase 2 of this study will shed light on these issues. Caution should be exercised, however, against overstating or understating the risks of deep brain stimulation for patients with PD. Physicians must continue to weigh the potential short-term and long-term risks with the benefits of deep brain stimulation in each patient.



Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response;

  These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder

Auto-generated: 13 January 2009 05:01


January 16, 2009 - Posted by | Uncategorized |

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